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Fulltext Bioactive Proteins in Channa striata Promote Wound Healing through Angiogenesis and Cell Proliferation

Kwan SH, Abdul Aziz NHK, Ismail MN

Protein Pept Lett, 2020;27(1):48-59.
PMID: 31362651 DOI: 10.2174/0929866526666190730121711

BACKGROUND: Channa striata are speculated to contain bioactive proteins with the ability to enhancing wound healing. It is commonly consumed after surgery for a faster recovery of the wound.
OBJECTIVE: To identify the bioactive proteins and evaluate their ability in cell proliferation and angiogenesis promotion.
MATERIAL AND METHODS: Freeze-Dried Water Extracts (FDWE) and Spray-Dried Water Extracts (SDWE) of C. striata were tested with MTT assay using EA.hy926 endothelial cell line and ex-vivo aortic ring assay. Later the proteins were fractionated and analysed using an LC-QTOF mass spectrometer. The data generated were matched with human gene database for protein similarity and pathway identification.
RESULTS: Both samples have shown positive cell proliferation and pro-angiogenic activity. Four essential proteins/genes were identified, which are collagen type XI, actin 1, myosin light chain and myosin heavy chain. The pathways discovered that related to these proteins are integrin pathway, Slit-Robo signalling pathway and immune response C-C Chemokine Receptor-3 signalling pathway in eosinophils, which contribute towards wound healing mechanism.
CONCLUSIONS: The results presented have demonstrated that C. striata FDWE and SDWE protein fractions contain bioactive proteins that are highly similar to human proteins and thus could be involved in the wound healing process via specific biological pathways.

Matched MeSH terms: Integrins/metabolism
Fulltext Multimeric disintegrin protein polymer fusions that target tumor vasculature

Janib SM, Gustafson JA, Minea RO, Swenson SD, Liu S, Pastuszka MK, et al.

Biomacromolecules, 2014 Jul 14;15(7):2347-58.
PMID: 24871936 DOI: 10.1021/bm401622y

Recombinant protein therapeutics have increased in number and frequency since the introduction of human insulin, 25 years ago. Presently, proteins and peptides are commonly used in the clinic. However, the incorporation of peptides into clinically approved nanomedicines has been limited. Reasons for this include the challenges of decorating pharmaceutical-grade nanoparticles with proteins by a process that is robust, scalable, and cost-effective. As an alternative to covalent bioconjugation between a protein and nanoparticle, we report that biologically active proteins may themselves mediate the formation of small multimers through steric stabilization by large protein polymers. Unlike multistep purification and bioconjugation, this approach is completed during biosynthesis. As proof-of-principle, the disintegrin protein called vicrostatin (VCN) was fused to an elastin-like polypeptide (A192). A significant fraction of fusion proteins self-assembled into multimers with a hydrodynamic radius of 15.9 nm. The A192-VCN fusion proteins compete specifically for cell-surface integrins on human umbilical vein endothelial cells (HUVECs) and two breast cancer cell lines, MDA-MB-231 and MDA-MB-435. Confocal microscopy revealed that, unlike linear RGD-containing protein polymers, the disintegrin fusion protein undergoes rapid cellular internalization. To explore their potential clinical applications, fusion proteins were characterized using small animal positron emission tomography (microPET). Passive tumor accumulation was observed for control protein polymers; however, the tumor accumulation of A192-VCN was saturable, which is consistent with integrin-mediated binding. The fusion of a protein polymer and disintegrin results in a higher intratumoral contrast compared to free VCN or A192 alone. Given the diversity of disintegrin proteins with specificity for various cell-surface integrins, disintegrin fusions are a new source of biomaterials with potential diagnostic and therapeutic applications.

Matched MeSH terms: Integrins/metabolism
MicroRNAs associated with tumour migration, invasion and angiogenic properties in A549 and SK-Lu1 human lung adenocarcinoma cells

Ho CS, Yap SH, Phuah NH, In LL, Hasima N

Lung Cancer, 2014 Feb;83(2):154-62.
PMID: 24360396 DOI: 10.1016/j.lungcan.2013.11.024

Dysregulation in miRNA expression contributes towards the initiation and progression of metastasis by regulating multiple target genes. In this study, variations in miRNA expression profiles were investigated between high and low invasive NSCLC cell lines followed by identification of miRNAs with targets governing NSCLC's metastatic potential.

Matched MeSH terms: Integrins/metabolism
Regulatory actions of 3',5'-cyclic adenosine monophosphate on osteoclast function: possible roles of Epac-mediated signaling

Jeevaratnam K, Salvage SC, Li M, Huang CL

Ann N Y Acad Sci, 2018 Dec;1433(1):18-28.
PMID: 29846007 DOI: 10.1111/nyas.13861

Alterations in cellular levels of the second messenger 3',5'-cyclic adenosine monophosphate ([cAMP]i ) regulate a wide range of physiologically important cellular signaling processes in numerous cell types. Osteoclasts are terminally differentiated, multinucleated cells specialized for bone resorption. Their systemic regulator, calcitonin, triggers morphometrically and pharmacologically distinct retraction (R) and quiescence (Q) effects on cell-spread area and protrusion-retraction motility, respectively, paralleling its inhibition of bone resorption. Q effects were reproduced by cholera toxin-mediated Gs -protein activation known to increase [cAMP]i , unaccompanied by the [Ca2+ ]i changes contrastingly associated with R effects. We explore a hypothesis implicating cAMP signaling involving guanine nucleotide-exchange activation of the small GTPase Ras-proximate-1 (Rap1) by exchange proteins directly activated by cAMP (Epac). Rap1 activates integrin clustering, cell adhesion to bone matrix, associated cytoskeletal modifications and signaling processes, and transmembrane transduction functions. Epac activation enhanced, whereas Epac inhibition or shRNA-mediated knockdown compromised, the appearance of markers for osteoclast differentiation and motility following stimulation by receptor activator of nuclear factor kappa-Β ligand (RANKL). Deficiencies in talin and Rap1 compromised in vivo bone resorption, producing osteopetrotic phenotypes in genetically modified murine models. Translational implications of an Epac-Rap1 signaling hypothesis in relationship to N-bisphosphonate actions on prenylation and membrane localization of small GTPases are discussed.

Matched MeSH terms: Integrins/metabolism