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  1. Fulltext Inhibition of matrix metalloproteinases: a troubleshooting for dentin adhesion
    de Moraes IQS, do Nascimento TG, da Silva AT, de Lira LMSS, Parolia A, Porto ICCM
    Restor Dent Endod, 2020 Aug;45(3):e31.
    PMID: 32839712 DOI: 10.5395/rde.2020.45.e31
    Matrix metalloproteinases (MMPs) are enzymes that can degrade collagen in hybrid layer and reduce the longevity of adhesive restorations. As scientific understanding of the MMPs has advanced, useful strategies focusing on preventing these enzymes' actions by MMP inhibitors have quickly developed in many medical fields. However, in restorative dentistry, it is still not well established. This paper is an overview of the strategies to inhibit MMPs that can achieve a long-lasting material-tooth adhesion. Literature search was performed comprehensively using the electronic databases: PubMed, ScienceDirect and Scopus including articles from May 2007 to December 2019 and the main search terms were "matrix metalloproteinases", "collagen", and "dentin" and "hybrid layer". MMPs typical structure consists of several distinct domains. MMP inhibitors can be divided into 2 main groups: synthetic (synthetic-peptides, non-peptide molecules and compounds, tetracyclines, metallic ions, and others) and natural bioactive inhibitors mainly flavonoids. Selective inhibitors of MMPs promise to be the future for specific targeting of preventing dentin proteolysis. The knowledge about MMPs functionality should be considered to synthesize drugs capable to efficiently and selectively block MMPs chemical routes targeting their inactivation in order to overcome the current limitations of the therapeutic use of MMPs inhibitors, i.e., easy clinical application and long-lasting effect.
    Matched MeSH terms: Proteolysis
  2. TMT-labeled quantitative proteomic reveals the mechanism of proteolysis and taste improvement of dry-cured bacon with Staphylococcus co-inoculation
    Zhou C, Wu X, Pan D, Xia Q, Sun Y, Geng F, et al.
    Food Chem, 2024 Mar 15;436:137711.
    PMID: 37839122 DOI: 10.1016/j.foodchem.2023.137711
    To understand the mechanism of co-inoculation of Staphylococcus xylosus and Staphylococcus vitulinus (SX & SV) on structural protein degradation and taste enhancement of dry-cured bacon, protease activities, protein degradation, surface morphology of proteins and taste parameters of dry-cured bacon with Staphylococcus inoculation were investigated. The dry-cured bacon with co-inoculation of Staphylococcus xylosus and Staphylococcus vitulinus showed the best taste attributes. High residual activities in cathepsin B + L (more than 1.6-fold) and alanyl aminopeptidase (more than 1.4-fold) accelerated structural protein degradation in SX & SV. 32 down-regulated proteins were identified in SX & SV by TMT-labeled quantitative proteomic compared with control group; myosin and actin showed the most intense response to the accumulation of sweet and umami amino acids, and atomic force microscopy confirmed structural proteins breakdown by morphological changes. The accumulation of glutamic acid, alanine and lysine was mainly responsible for taste improvement of dry-cured bacon with Staphylococcus co-inoculation.
    Matched MeSH terms: Proteolysis
  3. Miltefosine suppression of Pten null T-ALL leukemia via β-catenin degradation through inhibition of pT308-Akt and TGFβ1/Smad3
    Zhang Y, Lee S, Xu W
    Biochem Biophys Res Commun, 2020 04 16;524(4):1018-1024.
    PMID: 32063363 DOI: 10.1016/j.bbrc.2020.02.021
    Pten deletion in the hematopoietic stem cells (HSC) causes a myeloproliferative disorder, which may subsequently develop into a T-cell acute lymphoblastic leukemia (T-ALL). β-catenin expression was dramatically increased in the c-KitmidCD3+Lin- leukemia stem cells (LSC) and was critical for T-ALL development. Therefore, the inactivation of β-catenin in LSC may have a potential to eliminate the LSC. In this study, we investigated the mechanism of enhancement of the β-catenin expression and subsequently used a drug to inactivate β-catenin expression in T-ALL. Western blot (WB) analysis revealed an increased level of β-catenin in the leukemic cells, but not in the pre-leukemic cells. Furthermore, the WB analysis of the thymic cells from different stages of leukemia development showed that increased expression of β-catenin was not via the pS9-GSK3β signaling, but was dependent on the pT308-Akt activation. Miltefosine (Hexadecylphosphocholine) is the first oral anti-Leishmania drug, which is a phospholipid agent and has been shown to inhibit the PI3K/Akt activity. Treatment of the PtenΔ/Δ leukemic mice with Miltefosine for different durations demonstrated that the pT308-Akt and the β-catenin expressions were inhibited in the leukemia blast cells. Miltefosine treatment also suppressed the TGFβ1/Smad3 signaling pathway. Analysis of TGFβ1 in the sorted subpopulations of the blast cells showed that TGFβ1 was secreted by the CD3+CD4- subpopulation and may exert effects on the subpopulations of both CD3+CD4+ and CD3+CD4- leukemia blast cells. When a TGFβR1 inhibitor, SB431542 was injected into the PtenΔ/Δ leukemic mice, the Smad3 and β-catenin expressions were down-regulated. On the basis of the results, we conclude that Miltefosine can suppress leukemia by degrading β-catenin through repression of the pT308-Akt and TGFβ1/Smad3 signaling pathways. This study demonstrates a possibility to inhibit Pten loss-associated leukemia genesis via targeting Akt and Smad3.
    Matched MeSH terms: Proteolysis/drug effects*
  4. Fulltext Production of defatted palm kernel cake protein hydrolysate as a valuable source of natural antioxidants
    Zarei M, Ebrahimpour A, Abdul-Hamid A, Anwar F, Saari N
    Int J Mol Sci, 2012;13(7):8097-111.
    PMID: 22942692 DOI: 10.3390/ijms13078097
    The aim of this study was to produce a valuable protein hydrolysate from palm kernel cake (PKC) for the development of natural antioxidants. Extracted PKC protein was hydrolyzed using different proteases (alcalase, chymotrypsin, papain, pepsin, trypsin, flavourzyme, and bromelain). Subsequently, antioxidant activity and degree of hydrolysis (DH) of each hydrolysate were evaluated using DPPH• radical scavenging activity and O-phthaldialdehyde spectrophotometric assay, respectively. The results revealed a strong correlation between DH and radical scavenging activity of the hydrolysates, where among these, protein hydrolysates produced by papain after 38 h hydrolysis exhibited the highest DH (91 ± 0.1%) and DPPH• radical scavenging activity (73.5 ± 0.25%) compared to the other hydrolysates. In addition, fractionation of the most effective (potent) hydrolysate by reverse phase high performance liquid chromatography indicated a direct association between hydrophobicity and radical scavenging activity of the hydrolysates. Isoelectric focusing tests also revealed that protein hydrolysates with basic and neutral isoelectric point (pI) have the highest radical scavenging activity, although few fractions in the acidic range also exhibited good antioxidant potential.
    Matched MeSH terms: Proteolysis
  5. The aminopeptidase inhibitor, z-L-CMK, is toxic and induces cell death in Jurkat T cells through oxidative stress
    Yeo EH, Goh WL, Chow SC
    Toxicol. Mech. Methods, 2018 Mar;28(3):157-166.
    PMID: 28849708 DOI: 10.1080/15376516.2017.1373882
    The leucine aminopeptidase inhibitor, benzyloxycarbonyl-leucine-chloromethylketone (z-L-CMK), was found to be toxic and readily induce cell death in Jurkat T cells. Dose-response studies show that lower concentration of z-L-CMK induced apoptosis in Jurkat T cells whereas higher concentration causes necrosis. In z-L-CMK-induced apoptosis, both the initiator caspases (-8 and -9) and effector caspases (-3 and -6) were processed to their respective subunits. However, the caspases remained intact in z-L-CMK-induced necrosis. The caspase inhibitor, z-VAD-FMK inhibited z-L-CMK-mediated apoptosis and caspase processing but has no effect on z-L-CMK-induced necrosis in Jurkat T cells. The high mobility group protein B1 (HMGB1) protein was found to be released into the culture medium by the necrotic cells and not the apoptotic cells. These results indicate that the necrotic cell death mediated by z-L-CMK at high concentrations is via classical necrosis rather than secondary necrosis. We also demonstrated that cell death mediated by z-L-CMK was associated with oxidative stress via the depletion of intracellular glutathione (GSH) and increase in reactive oxygen species (ROS), which was blocked by N-acetyl cysteine. Taken together, the results demonstrated that z-L-CMK is toxic to Jurkat T cells and induces apoptosis at low concentrations, while at higher concentrations the cells die of necrosis. The toxic side effects in Jurkat T cells mediated by z-L-CMK are associated with oxidative stress via the depletion of GSH and accumulation of ROS.
    Matched MeSH terms: Proteolysis/drug effects
  6. Umbilical Cord Mesenchymal Stem Cells Conditioned Medium Promotes Aβ25-35 phagocytosis by Modulating Autophagy and Aβ-Degrading Enzymes in BV2 Cells
    Xu Z, Nan W, Zhang X, Sun Y, Yang J, Lu K, et al.
    J Mol Neurosci, 2018 Jun;65(2):222-233.
    PMID: 29845511 DOI: 10.1007/s12031-018-1075-5
    Mesenchymal stem cell (MSC) therapy is a promising prospect for the treatment of Alzheimer's disease (AD); however, the underlying mechanisms by which MSCs mediate positive effects are still unclear. We speculated that MSCs mediate microglial autophagy and enhance the clearance of Aβ. To test this hypothesis, we cultured BV2 microglial cells with umbilical cord mesenchymal stem cells conditioned medium (ucMSCs-CM) in the presence or absence of Aβ25-35 oligomers. We investigated BV2 cell proliferation, cell death, and Aβ25-35 phagocytosis as well as protein expression levels of LC3, Beclin-1, p62, insulin-degrading enzyme (IDE), and neprilysin (Nep) with western blotting. The results showed that ucMSCs-CM inhibited the proliferation and decreased cell death of BV2 cells induced by Aβ25-35. ucMSCs-CM also promoted the phagocytosis of Aβ25-35 by BV2 cells and changed the expression of autophagy-related proteins LC3, Beclin-1, and p62. Treatment also upregulated the expression of Aβ-degrading enzymes IDE and Nep. Furthermore, the culture medium in BV2 cells with Aβ25-35 and ucMSCs-CM prevented neuronal cell SH-SY5Y from cell death compared to control medium without ucMSCs-CM. Altogether, these data suggested that ucMSCs-CM protect microglial and neuronal cells from Aβ25-35-induced cell death and promote Aβ phagocytosis by modulating autophagy and enhancing the expression of Aβ-degrading enzymes in microglia.
    Matched MeSH terms: Proteolysis*
  7. Mucoadhesive Low Molecular Chitosan Complexes to Protect rHuKGF from Proteolysis: In-vitro Characterization and FHs 74 Int Cell Proliferation Studies
    Tee YN, Kumar PV, Maki MAA, Elumalai M, Rahman SAKMEH, Cheah SC
    Curr Pharm Biotechnol, 2021;22(7):969-982.
    PMID: 33342408 DOI: 10.2174/1389201021666201218124450
    BACKGROUND: Recombinant Keratinocyte Growth Factor (rHuKGF) is a therapeutic protein used widely in oral mucositis after chemotherapy in various cancers, stimulating lung morphogenesis and gastrointestinal tract cell proliferation. In this research study, chitosan-rHuKGF polymeric complex was implemented to improve the stability of rHuKGF and used as rejuvenation therapy for the treatment of oral mucositis in cancer patients.

    OBJECTIVE: Complexation of rHuKGF with mucoadhesive low molecular weight chitosan to protect rHuKGF from proteolysis and investigate the effect of chitosan-rHuKGF complex on the proliferation rate of FHs 74 Int cells.

    METHODS: The interaction between chitosan and rHuKGF was studied by molecular docking. Malvern ZetaSizer Nano Zs and Fourier-Transform Infrared spectroscopy (FTIR) tests were carried out to characterize the chitosan-rHuKGF complex. In addition, SDS-PAGE was performed to investigate the interaction between chitosan-rHuKGF complex and pepsin. The effect of chitosan-rHuKGF complex on the proliferation rate of FHs 74 Int cells was studied by MTT assay.

    RESULTS: Chitosan-rHuKGF complex was formed through the hydrogen bonding proven by the docking studies. A stable chitosan-rHuKGF complex was formed at pH 4.5 and was protected from proteolysis and assessed by SDS PAGE. According to the MTT assay results, chitosan-rHuKGF complex increased the cell proliferation rate of FHs 74 Int cells.

    CONCLUSION: The developed complex improved the stability and the biological function of rHuKGF.

    Matched MeSH terms: Proteolysis/drug effects*
  8. KSR1 regulates BRCA1 degradation and inhibits breast cancer growth
    Stebbing J, Zhang H, Xu Y, Lit LC, Green AR, Grothey A, et al.
    Oncogene, 2015 Apr 16;34(16):2103-14.
    PMID: 24909178 DOI: 10.1038/onc.2014.129
    Kinase suppressor of Ras-1 (KSR1) facilitates signal transduction in Ras-dependent cancers, including pancreatic and lung carcinomas but its role in breast cancer has not been well studied. Here, we demonstrate for the first time it functions as a tumor suppressor in breast cancer in contrast to data in other tumors. Breast cancer patients (n>1000) with high KSR1 showed better disease-free and overall survival, results also supported by Oncomine analyses, microarray data (n=2878) and genomic data from paired tumor and cell-free DNA samples revealing loss of heterozygosity. KSR1 expression is associated with high breast cancer 1, early onset (BRCA1), high BRCA1-associated ring domain 1 (BARD1) and checkpoint kinase 1 (Chk1) levels. Phospho-profiling of major components of the canonical Ras-RAF-mitogen-activated protein kinases pathway showed no significant changes after KSR1 overexpression or silencing. Moreover, KSR1 stably transfected cells formed fewer and smaller size colonies compared to the parental ones, while in vivo mouse model also demonstrated that the growth of xenograft tumors overexpressing KSR1 was inhibited. The tumor suppressive action of KSR1 is BRCA1 dependent shown by 3D-matrigel and soft agar assays. KSR1 stabilizes BRCA1 protein levels by reducing BRCA1 ubiquitination through increasing BARD1 abundance. These data link these proteins in a continuum with clinical relevance and position KSR1 in the major oncoprotein pathways in breast tumorigenesis.
    Matched MeSH terms: Proteolysis
  9. Natural DENV-2 NS2B/NS3 protease inhibitors from Myristica cinnamomea King
    Sivasothy Y, Liew SY, Othman MA, Abdul Wahab SM, Hariono M, Mohd Nawi MS, et al.
    Trop Biomed, 2021 Jun 01;38(2):79-84.
    PMID: 33973577 DOI: 10.47665/tb.38.2.044
    The NS2B/NS3 protease is crucial for the pathogenesis of the DENV. Therefore, the inhibition of this protease is considered to be the key strategy for the development of new antiviral drugs. In the present study, malabaricones C (3) and E (4), acylphenols from the fruits of Myristica cinnamomea King, have been respectively identified as moderate (27.33 ± 5.45 μM) and potent (7.55 ± 1.64 μM) DENV-2 NS2B/NS3 protease inhibitors, thus making this the first report on the DENV-2 NS2B/NS3 protease inhibitory activity of acylphenols. Based on the molecular docking studies, compounds 3 and 4 both have π-π interactions with Tyr161. While compound 3 has hydrogen bonding interactions with Gly151, Gly153 and Tyr161, compound 4 however, forms hydrogen bonds with Ser135, Asp129, Phe130 and Ile86 instead. The results from the present study suggests that malabaricones C (3) and E (4) could be employed as lead compounds for the development of new dengue antivirals from natural origin.
    Matched MeSH terms: Proteolysis
  10. The effect of peptidic and non-peptidic proteasome inhibitors on the biological properties of Acanthamoeba castellanii belonging to the T4 genotype
    Siddiqui R, Saleem S, Khan NA
    Exp Parasitol, 2016 Jun 18;168:16-24.
    PMID: 27327524 DOI: 10.1016/j.exppara.2016.06.006
    The treatment of Acanthamoeba infections remains problematic, suggesting that new targets and/or chemotherapeutic agents are needed. Bioassay-guided screening of drugs that are clinically-approved for non-communicable diseases against opportunistic eukaryotic pathogens is a viable strategy. With known targets and mode of action, such drugs can advance to clinical trials at a faster pace. Recently Bortezomib (proteasome inhibitor) has been approved by FDA in the treatment of multiple myeloma. As proteasomal pathways are well known regulators of a variety of eukaryotic cellular functions, the overall aim of the present study was to study the effects of peptidic and non-peptidic proteasome inhibitors on the biology and pathogenesis of Acanthamoeba castellanii of the T4 genotype, in vitro. Zymographic assays revealed that inhibition of proteasome had detrimental effects on the extracellular proteolytic activities of A. castellanii. Proteasome inhibition affected A. castellanii growth (using amoebistatic assays), but not viability of A. castellanii. Importantly, proteasome inhibitors affected encystation as determined by trophozoite transformation into the cyst form, as well as excystation, as determined by cyst transformation into the trophozoite form. The ability of proteasome inhibitor to block Acanthamoeba differentiation is significant, as it presents a major challenge in the successful treatment of Acanthamoeba infection. As these drugs are used clinically against non-communicable diseases, the findings reported here have the potential to be tested in a clinical setting against amoebic infections.
    Matched MeSH terms: Proteolysis
  11. Proteolytic profile, angiotensin-I converting enzyme inhibitory activity and sensory evaluation of Codonopsis pilosula and fish collagen cheese
    Shori AB, Hong YC, Baba AS
    Food Res Int, 2021 05;143:110238.
    PMID: 33992351 DOI: 10.1016/j.foodres.2021.110238
    Four types of cheeses were prepared included plain- cheese (control), Codonopsis pilosula (CP)- cheese, plain- cheese with fish collagen (FC; control) and CP- cheese with FC. The effects of cheese samples on acidification, proteolysis of milk proteins using three methods (cadmium-ninhydrin method, O-phthaldialdehyde (OPA) assay, and electrophoresis assay), and angiotensin-converting enzyme (ACE)-inhibitory activity were investigated during 0, 2, & 4 weeks of ripening. In addition, the sensory evaluation was also investigated during 0, 2, 4, & 8 weeks of ripening. The presence of FC in CP- cheese increased the numbers of free amino acids (FAA) at 0 and 2 weeks. The addition of CP both in the presence and absence of FC affected positively (p 
    Matched MeSH terms: Proteolysis
  12. The effects of Lycium barbarum water extract and fish collagen on milk proteolysis and in vitro angiotensin I-converting enzyme inhibitory activity of yogurt
    Shori AB, Ming KS, Baba AS
    Biotechnol Appl Biochem, 2021 Apr;68(2):221-229.
    PMID: 32249982 DOI: 10.1002/bab.1914
    Plain and Lycium barbarum yogurt were made in the presence and absence of fish collagen. Yogurt samples were analyzed for acidification, milk protein proteolysis, angiotensin I-converting enzyme (ACE) inhibitory activity, and sensory evaluation during refrigerated storage for up to 21 days. The o-phthaldialdehyde peptides amount of L. barbarum yogurt both in the presence and absence of fish collagen were significantly increased during 14 days of storage. SDS-PAGE showed improvement in whey proteins degradation of L. barbarum yogurt with/without fish collagen after 3 weeks of storage. L. barbarum yogurt in absence of fish collagen was acting as a great ACE inhibitor reached up to 85% on day 7 of storage. The incorporation of L. barbarum and/or fish collagen affected to a small extent the overall sensory characteristics of yogurt. Yogurt supplemented with L. barbarum and/or fish collagen may lead to the improvement in the production and formulation of yogurt differing in their anti-ACE activity.
    Matched MeSH terms: Proteolysis*
  13. Effect of Allium sativum and fish collagen on the proteolytic and angiotensin-I converting enzyme-inhibitory activities in cheese and yogurt
    Shori AB, Baba AS, Keow JN
    Pak J Biol Sci, 2012 Dec 15;15(24):1160-7.
    PMID: 23755406
    There is an increasing demand of functional foods in developed countries. Yogurt plays an important role in the management of blood pressure. Several bioactive peptides isolated from Allium sativum or fish collagen have shown antihypertensive activity. Thus, in the present study the effects of A. sativum and/or Fish Collagen (FC) on proteolysis and ACE inhibitory activity in yogurt (0, 7 and 14 day) and cheese (0, 14 and 28 day) were investigated. Proteolytic activities were the highest on day 7 of refrigerated storage in A. sativum-FC-yogurt (337.0 +/- 5.3 microg g(-1)) followed by FC-yogurt (275.3 +/- 2.0 microg g(-1)), A. sativum-yogurt (245.8 +/- 4.2 microg g(-1)) and plain-yogurt (40.4 +/- 1.2 microg g(-1)). On the other hand, proteolytic activities in cheese ripening were the highest (p < 0.05) on day 14 of storage for plain and A. sativum-cheeses (411.4 +/- 4.3 and 528.7 +/- 1.6 microg g(-1), respectively). However, the presence of FC increased the proteolysis to the highest level on day 28 of storage for FC- and A. sativum-FC cheeses (641.2 +/- 0.1 and 1128.4 +/- 4.5 microg g(-1), respectively). In addition, plain- and A. sativum-yogurts with or without FC showed maximal inhibition of ACE on day 7 of storage. Fresh plain- and A. sativum-cheeses showed ACE inhibition (72.3 +/- 7.8 and 50.4 +/- 1.6 % respectively), the presence of FC in both type of cheeses reduced the ACE inhibition to 62.9 +/- 0.8 and 44.5 +/- 5.0%, respectively. However, refrigerated storage increased ACE inhibition in cheeses (p < 0.05 on day 28) in the presence of FC more than in the absence. In conclusion, the presence of FC in A. sativum-yogurt or cheese enhanced the proteolytic activity. Thus, it has potential in the development of an effective dietary strategy for hypertension associated cardiovascular diseases.
    Matched MeSH terms: Proteolysis
  14. Fulltext Regulation of Proteolytic Activity to Improve the Recovery of Macrobrachium rosenbergii Nodavirus Capsid Protein
    Selvaraj BA, Mariatulqabtiah AR, Ho KL, Ng CL, Yong CY, Tan WS
    Int J Mol Sci, 2021 Aug 13;22(16).
    PMID: 34445426 DOI: 10.3390/ijms22168725
    The causative agent of white tail disease (WTD) in the giant freshwater prawn is Macrobrachium rosenbergii nodavirus (MrNV). The recombinant capsid protein (CP) of MrNV was previously expressed in Escherichia coli, and it self-assembled into icosahedral virus-like particles (VLPs) with a diameter of approximately 30 nm. Extensive studies on the MrNV CP VLPs have attracted widespread attention in their potential applications as biological nano-containers for targeted drug delivery and antigen display scaffolds for vaccine developments. Despite their advantageous features, the recombinant MrNV CP VLPs produced in E. coli are seriously affected by protease degradations, which significantly affect the yield and stability of the VLPs. Therefore, the aim of this study is to enhance the stability of MrNV CP by modulating the protease degradation activity. Edman degradation amino acid sequencing revealed that the proteolytic cleavage occurred at arginine 26 of the MrNV CP. The potential proteases responsible for the degradation were predicted in silico using the Peptidecutter, Expasy. To circumvent proteolysis, specific protease inhibitors (PMSF, AEBSF and E-64) were tested to reduce the degradation rates. Modulation of proteolytic activity demonstrated that a cysteine protease was responsible for the MrNV CP degradation. The addition of E-64, a cysteine protease inhibitor, remarkably improved the yield of MrNV CP by 2.3-fold compared to the control. This innovative approach generates an economical method to improve the scalability of MrNV CP VLPs using individual protease inhibitors, enabling the protein to retain their structural integrity and stability for prominent downstream applications including drug delivery and vaccine development.
    Matched MeSH terms: Proteolysis/drug effects
  15. Recent advances in food biopeptides: production, biological functionalities and therapeutic applications
    Saadi S, Saari N, Anwar F, Abdul Hamid A, Ghazali HM
    Biotechnol Adv, 2014 12 12;33(1):80-116.
    PMID: 25499177 DOI: 10.1016/j.biotechadv.2014.12.003
    The growing momentum of several common life-style diseases such as myocardial infarction, cardiovascular disorders, stroke, hypertension, diabetes, and atherosclerosis has become a serious global concern. Recent developments in the field of proteomics offering promising solutions to solving such health problems stimulates the uses of biopeptides as one of the therapeutic agents to alleviate disease-related risk factors. Functional peptides are typically produced from protein via enzymatic hydrolysis under in vitro or in vivo conditions using different kinds of proteolytic enzymes. An array of biological activities, including antioxidative, antihypertensive, antidiabetic and immunomodulating has been ascribed to different types of biopeptides derived from various food sources. In fact, biopeptides are nutritionally and functionally important for regulating some physiological functions in the body; however, these are yet to be extensively addressed with regard to their production through advance strategies, mechanisms of action and multiple biological functionalities. This review mainly focuses on recent biotechnological advances that are being made in the field of production in addition to covering the mode of action and biological activities, medicinal health functions and therapeutic applications of biopeptides. State-of-the-art strategies that can ameliorate the efficacy, bioavailability, and functionality of biopeptides along with their future prospects are likewise discussed.
    Matched MeSH terms: Proteolysis
  16. Smart electrical bi-layers lipopeptides: Novel peptidic chains like zigzag map esterified with phospho-glyceride as mono-layer moieties capable in forming a meso-sphere- envelop with scaffold- ability to cellular impurities
    Saadi S, Saari N, Abdulkarim MS, Ghazali HM, Anwar F
    J Control Release, 2018 03 28;274:93-101.
    PMID: 29031897 DOI: 10.1016/j.jconrel.2017.10.011
    Cell impurities are an emerging nucleating molecular barriers having the capability in disordering the metabolic chain reactions of proteolysis, glycolysis and lipolysis. Their massive effects induced by copolymer crystal growth in compaction with metal and mineral transients are extended as well as in damaging DNA and mRNA structure motif and other molecular assembly e.g. histones structure unites. Their polycrystalline packing modes, polydispersity and their tendency to surface and interface adhesion prompted us in structuring scaffold biomaterials enriched with biopeptides, layered by phospho-glycerides ester-forms. The interface tension of the formed map is flexible and dependent to the surface exposure and its collapse modes to the surrounding molecular ligands. Thus, the attempts in increasing surface exposure e.g. the viscoelastic of structured lipopeptides and types of formed network structures interplays an extra- conjugating biomolecules having a least cytotoxicity effects to cells constituents. Disulfides molecules are selected to be the key regulatory element in rejoining both lipidic and proteic moieties by disordering atoms status via chemical ionization using organic catalyst. The insertion of methionine based peptidic chain at the lateral surfaces of scaffold biomaterials enhances the electron-meta-static motions by raising a molecular disordering status at distinct regions of the map e.g. epimerization into a nonpolar side that helps the chemical conjunction of disulfide groups with the esterified phosphoglycerides mono-layers. These effects in turn are accomplished by the formation of meso-sphere nonpolar- vesicles. The oxidation of disulfide group would alter the ordering of initial molecules by raising a newly molecular disorders to the map with high polarity to surface regions. In the same time indicates a continuation in the crystallization growth factor via a low chemical lesions between the impurities and a supersaturation in the intra-atomic distances with maximum cross linking to the deformed ligand with scaffold biomaterials.
    Matched MeSH terms: Proteolysis
  17. Fulltext Identification of small molecule inhibitors of p27(Kip1) ubiquitination by high-throughput screening
    Ooi LC, Watanabe N, Futamura Y, Sulaiman SF, Darah I, Osada H
    Cancer Sci, 2013 Nov;104(11):1461-7.
    PMID: 23910095 DOI: 10.1111/cas.12246
    Dysregulation of p27(Kip1) due to proteolysis that involves the ubiquitin ligase (SCF) complex with S-phase kinase-associated protein 2 (Skp2) as the substrate-recognition component (SCF(Skp2)) frequently results in tumorigenesis. In this report, we developed a high-throughput screening system to identify small-molecule inhibitors of p27(Kip1) degradation. This system was established by tagging Skp2 with fluorescent monomeric Azami Green (mAG) and CDK subunit 1 (Cks1) (mAGSkp2-Cks1) to bind to p27(Kip1) phosphopeptides. We identified two compounds that inhibited the interaction between mAGSkp2-Cks1 and p27(Kip1): linichlorin A and gentian violet. Further studies have shown that the compounds inhibit the ubiquitination of p27(Kip1) in vitro as well as p27(Kip1) degradation in HeLa cells. Notably, both compounds exhibited preferential antiproliferative activity against HeLa and tsFT210 cells compared with NIH3T3 cells and delayed the G1 phase progression in tsFT210 cells. Our approach indicates a potential strategy for restoring p27(Kip1) levels in human cancers.
    Matched MeSH terms: Proteolysis/drug effects
  18. Fulltext Kolaviron Protects the Prefrontal Cortex and Hippocampus against Histomorphological and Neurobehavioural Changes in Cuprizone Model of Multiple Sclerosis
    Omotoso GO, Olajide OJ, Gbadamosi IT, Rasheed MA, Izuogu CT
    Malays J Med Sci, 2018 Mar;25(2):50-63.
    PMID: 30918455 DOI: 10.21315/mjms2018.25.2.6
    Background: This study explored the efficacy of kolaviron-a biflavonoid complex isolated from the seeds of Garcinia kola-in protecting against cuprizone (CPZ)-induced demyelination in both the prefrontal cortex and the hippocampus of Wistar rats.

    Methodology: Thirty rats were treated to receive 0.5 mL phosphate-buffered saline (group A, control), 0.5 mL corn oil (group B), 0.2% CPZ (group C), for 6 weeks, 0.2% CPZ for 3 weeks and then 200 mg/kg of Kv for 3 weeks (group D), or 200 mg/kg of Kv for 3 weeks followed by 0.2% CPZ for 3 weeks (group E). Rats were assessed for exploratory functions and anxiety-like behaviour before being euthanised and perfused transcardially with 4% paraformaldehyde. Prefrontal and hippocampal thin sections were stained in hematoxylin and eosin and cresyl fast violet stains.

    Results: CPZ-induced demyelination resulted in behavioural impairment as seen by reduced exploratory activities, rearing behaviour, stretch attend posture, center square entry, and anxiogenic characteristics. Degenerative changes including pyknosis, karyorrhexis, neuronal hypertrophy, and reduced Nissl integrity were also seen. Animals treated with Kv showed significant improvement in behavioural outcomes and a comparatively normal cytoarchitectural profile.

    Conclusion: Kv provides protective roles against CPZ-induced neurotoxicity through prevention of ribosomal protein degradation.

    Matched MeSH terms: Proteolysis
  19. Peg-4000 increased the mating efficiency of yeast-two hybrid screening process using pmf-box1 as bait
    Nur Athirah Abd Hamid, Ismanizan Ismail
    Sains Malaysiana, 2018;47:2961-2968.
    Protein degradation can occur through Ubiquitin 26S-Proteosome System (UPS). The degradation can be mediated by
    the SCF E3 ubiquitin ligase complex consisting of Skp1, Cullin, and F-box protein as the main components. The F-box
    protein at the C-terminal domain functions to recognize the targeted protein to be ubiquitinated and degraded via UPS.
    A stress-responsive F-box gene, PmF-box1 from Persicaria minor was categorized in the F-box containing kelch repeat
    (FBK) family; a family that specific to plant kingdom. To identify the targeted protein of PmF-box1, yeast-two hybrid system
    (Y2H) was used. In the Y2H screening process, mating efficiency is very important to fish out the interacting proteins.
    Therefore, one modification was conducted to increase the mating efficiency. In this screening, PmF-box1 was used as a
    bait to screen for the Y2H library which was constructed using RNA from plant samples treated with abscisic acid (ABA)
    and polyethylene glycol (PEG)-8000 and control sample. Autoactivation and toxicity tests of bait were performed before
    the Y2H screening. Tests on PmF-box1 showed that it is not toxic to the yeast and cannot autoactivate the yeast reporter
    genes. Mating efficiency was improved from 2.07% to 9.15% after addition of PEG-4000 in the mating culture compared
    to the original protocol, which it also increased the colony number in the screening step afterward. Additionally, bands
    of gene with different sizes were observed on electrophoresis gel after colony PCR analysis from the improved technique.
    Those genes may code for potential interacting proteins that needs further identification and confirmation.
    Matched MeSH terms: Proteolysis
  20. Enantiomeric pair of copper(II) polypyridyl-alanine complexes: Effect of chirality on their interaction with biomolecules
    Ng CH, Chan CW, Lai JW, Ooi IH, Chong KV, Maah MJ, et al.
    J Inorg Biochem, 2016 07;160:1-11.
    PMID: 27105312 DOI: 10.1016/j.jinorgbio.2016.04.003
    Like chiral organic drugs, the chemical and biological properties of metal complexes can be dependent on chirality. Two pairs of [Cu(phen)(ala)(H2O)]X·xH2O (phen=1.10-phenanthroline: X=NO3(-); ala: l-alanine (l-ala), 1 and d-alanine (d-ala) 2; and (X=Cl(-); ala: l-ala, 3 and d-ala, 4) complex salts (x=number of lattice water molecules) have been synthesized and characterized. The crystal structure of 3 has been determined. The same pair of enantiomeric species, viz. [Cu(phen)(l-ala)(H2O)](+) and [Cu(phen)(d-ala)(H2O)](+), have been identified to be present in the aqueous solutions of both 1 and 3, and in those of both 2 and 4 respectively. Both 3 and 4 bind more strongly to ds(AT)6 than ds(CG)6. There is no or insignificant effect of the chirality of 3 and 4 on the production of hydroxyl radicals, binding to deoxyribonucleic acid from calf thymus (CT-DNA), ds(CG)6, G-quadruplex and 17-base pair duplex, and inhibition of both topoisomerase I and proteasome. Among the three proteasome proteolytic sites, the trypsin-like site is inhibited most strongly by these complexes. However, the chirality of 3 and 4 does affect the number of restriction enzymes inhibited, and their binding constants towards ds(AT)6 and serum albumin.
    Matched MeSH terms: Proteolysis
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