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Determination of alpha-2-MRAP gene polymorphisms in nephrolithiasis patients

Mehde AA, Mehdi WA, Yusof F, Raus RA, Abidin ZAZ, Ghazali H, et al.

Int J Biol Macromol, 2017 Dec;105(Pt 1):1324-1327.
PMID: 28760704 DOI: 10.1016/j.ijbiomac.2017.07.167

BACKGROUND: The intron 5 insertion/deletion polymorphism of Alpha-2-macroglobulin receptor-associated protein gene (Alpha-2-MRAP) has been implicated in numerous diseases. The current study was designed to analyze the association of intron 5 insertion/deletion polymorphism of Alpha-2-MRAP with nephrolithiasis patients.
METHODS: PCR was conducted on genomic DNA of patients and control to look for Alpha-2-MRAP insertion/deletion polymorphism. Besides that, serum level of Alpha-2-MRAP, oxidative stress marker myeloperoxidase, Malondialdehyde (MDA), Advanced oxidation protein products (AOPP), and uric acid were determined.
RESULTS: The D and I allele frequencies were 57.50% and 42.50% in patients, 77.50% and 22.50% in control, individually. The result showed that II genotype was associated with nephrolithiasis patients group. A significant decrease was observed in serum Alpha-2-MRAP,myeloperoxidase and TAS,while TOS,OSI,MDA,AOPP and uric acid were substantially increased in II and ID when compared to DD genotype in patients with nephrolithiasis.
CONCLUSION: Our results demonstrate for the first time that patients with II genotype had an increased risk of stones. Also, the results demonstrate that I allele of the 5 insertion/deletion polymorphism in the Alpha-2-MRAP gene is related with an increase of oxidative stress in nephrolithiasis patients and may possibly impose a risk for cardiovascular diseases in patients with II genotype of Alpha-2-MRAP.

Matched MeSH terms: Oxidative Stress/genetics
Current anti-biofilm strategies and potential of antioxidants in biofilm control

Ong KS, Mawang CI, Daniel-Jambun D, Lim YY, Lee SM

Expert Rev Anti Infect Ther, 2018 11;16(11):855-864.
PMID: 30308132 DOI: 10.1080/14787210.2018.1535898

INTRODUCTION: Biofilm formation is a strategy for microorganisms to adapt and survive in hostile environments. Microorganisms that are able to produce biofilms are currently recognized as a threat to human health. Areas covered: Many strategies have been employed to eradicate biofilms, but several drawbacks from these methods had subsequently raised concerns on the need for alternative approaches to effectively prevent biofilm formation. One of the main mechanisms that drives a microorganism to transit from a planktonic to a biofilm-sessile state, is oxidative stress. Chemical agents that could target oxidative stress regulators, for instance antioxidants, could therefore be used to treat biofilm-associated infections. Expert commentary: The focus of this review is to summarize the function and limitation of the current anti-biofilm strategies and will propose the use of antioxidants as an alternative method to treat, prevent and eradicate biofilms. Studies have shown that water-soluble and lipid-soluble antioxidants can reduce and prevent biofilm formation, by influencing the expression of genes associated with oxidative stress. Further in vivo work should be conducted to ensure the efficacy of these antioxidants in a biological environment. Nevertheless, antioxidants are promising anti-biofilm agents, and thus is a potential solution for biofilm-associated infections in the future.

Matched MeSH terms: Oxidative Stress/genetics
Fulltext Oxidative Stress Down-Regulates MiR-20b-5p, MiR-106a-5p and E2F1 Expression to Suppress the G1/S Transition of the Cell Cycle in Multipotent Stromal Cells

Tai L, Huang CJ, Choo KB, Cheong SK, Kamarul T

Int J Med Sci, 2020;17(4):457-470.
PMID: 32174776 DOI: 10.7150/ijms.38832

Oxidative stress has been linked to senescence and tumorigenesis via modulation of the cell cycle. Using a hydrogen peroxide (H2O2)-induced oxidative stress-induced premature senescence (OSIPS) model previously reported by our group, this study aimed to investigate the effects of oxidative stress on microRNA (miRNA) expression in relation to the G1-to-S-phase (G1/S) transition of the cell cycle and cell proliferation. On global miRNA analysis of the OSIPS cells, twelve significantly up- or down-regulated miRNAs were identified, the target genes of which are frequently associated with cancers. Four down-regulated miR-17 family miRNAs are predicted to target key pro- and anti-proliferative proteins of the p21/cyclin D-dependent kinase (CDK)/E2F1 pathway to modulate G1/S transition. Two miR-17 miRNAs, miR-20-5p and miR-106-5p, were confirmed to be rapidly and stably down-regulated under oxidative stress. While H2O2 treatment hampered G1/S transition and suppressed DNA synthesis, miR-20b-5p/miR-106a-5p over-expression rescued cells from growth arrest in promoting G1/S transition and DNA synthesis. Direct miR-20b-5p/miR-106a-5p regulation of p21, CCND1 and E2F1 was demonstrated by an inverse expression relationship in miRNA mimic-transfected cells. However, under oxidative stress, E2F1 expression was down-regulated, consistent with hampered G1/S transition and suppressed DNA synthesis and cell proliferation. To explain the observed E2F1 down-regulation under oxidative stress, a scheme is proposed which includes miR-20b-5p/miR-106a-5p-dependent regulation, miRNA-E2F1 autoregulatory feedback and E2F1 response to repair oxidative stress-induced DNA damages. The oxidative stress-modulated expression of miR-17 miRNAs and E2F1 may be used to develop strategies to retard or reverse MSC senescence in culture, or senescence in general.

Matched MeSH terms: Oxidative Stress/genetics
An oxidatively stressful situation: a case of Artemisia annua L

Kam MYY, Yap WSP

Biotechnol Genet Eng Rev, 2020 Apr;36(1):1-31.
PMID: 32308142 DOI: 10.1080/02648725.2020.1749818

Artemisinin (ART) is an antimalarial compound that possesses a variety of novel biological activities. Due to the low abundance of ART in natural sources, agricultural supply has been erratic, and prices are highly volatile. While heterologous biosynthesis and semi-synthesis are advantageous in certain aspects, these approaches remained disadvantageous in terms of productivity and cost-effectiveness. Therefore, further improvement in ART production calls for approaches that should supplement the agricultural production gap, while reducing production costs and stabilising supply. The present review offers a discussion on the elicitation of plants and/or in vitro cultures as an economically feasible yield enhancement strategy to address the global problem of access to affordable ART. Deemed critical for the manipulation of biosynthetic potential, the mechanism of ART biosynthesis is reviewed. It includes a discussion on the current biotechnological solutions to ART production, focusing on semi-synthesis and elicitation. A brief commentary on the possible aspects that influence elicitation efficiency and how oxidative stress modulates ART synthesis is also presented. Based on the critical analysis of current literature, a hypothesis is put forward to explain the possible involvement of enzymes in assisting the final non-enzymatic transformation step leading to ART formation. This review highlights the critical factors limiting the success of elicitor-induced modulation of ART metabolism, that will help inform strategies for future improvement of ART production. Additionally, new avenues for future research based on the proposed hypothesis will lead to exciting perspectives in this research area and continue to enhance our understanding of this intricate metabolic process.

Matched MeSH terms: Oxidative Stress/genetics
Naegleria fowleri: differential genetic expression following treatment with Hesperidin conjugated with silver nanoparticles using RNA-Seq

Siddiqui R, Rajendran K, Abdella B, Ayub Q, Lim SY, Khan NA

Parasitol Res, 2020 Jul;119(7):2351-2358.
PMID: 32451717 DOI: 10.1007/s00436-020-06711-6

Naegleria fowleri causes a deadly infection known as primary amoebic meningoencephalitis (PAM). To our knowledge, there are very few transcriptome studies conducted on these brain-eating amoebae, despite rise in the number of cases. Although the Naegleria genome has been sequenced, currently, it is not well annotated. Transcriptome level studies are needed to help understand the pathology and biology of this fatal parasitic infection. Recently, we showed that nanoparticles loaded with the flavonoid Hesperidin (HDN) are potential novel antimicrobial agents. N. fowleri trophozoites were treated with and without HDN-conjugated with silver nanoparticles (AgNPs) and silver only, and then, 50% minimum inhibitory concentration (MIC) was determined. The results revealed that the MIC of HDN-conjugated AgNPs was 12.5 microg/mL when treated for 3 h. As no reference genome exists for N. fowleri, de novo RNA transcriptome analysis using RNA-Seq and differential gene expression analysis was performed using the Trinity software. Analysis revealed that more than 2000 genes were differentially expressed in response to N. fowleri treatment with HDN-conjugated AgNPs. Some of the genes were linked to oxidative stress response, DNA repair, cell division, cell signalling and protein synthesis. The downregulated genes were linked with processes such as protein modification, synthesis of aromatic amino acids, when compared with untreated N. fowleri. Further transcriptome studies will lead to understanding of genetic mechanisms of the biology and pathogenesis and/or the identification of much needed drug candidates.

Matched MeSH terms: Oxidative Stress/genetics
Fulltext Interleukin-6 is required for pancreatic cancer progression by promoting MAPK signaling activation and oxidative stress resistance

Zhang Y, Yan W, Collins MA, Bednar F, Rakshit S, Zetter BR, et al.

Cancer Res, 2013 Oct 15;73(20):6359-74.
PMID: 24097820 DOI: 10.1158/0008-5472.CAN-13-1558-T

Pancreatic cancer, one of the deadliest human malignancies, is almost invariably associated with the presence of an oncogenic form of Kras. Mice expressing oncogenic Kras in the pancreas recapitulate the stepwise progression of the human disease. The inflammatory cytokine interleukin (IL)-6 is often expressed by multiple cell types within the tumor microenvironment. Here, we show that IL-6 is required for the maintenance and progression of pancreatic cancer precursor lesions. In fact, the lack of IL-6 completely ablates cancer progression even in presence of oncogenic Kras. Mechanistically, we show that IL-6 synergizes with oncogenic Kras to activate the reactive oxygen species detoxification program downstream of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling cascade. In addition, IL-6 regulates the inflammatory microenvironment of pancreatic cancer throughout its progression, providing several signals that are essential for carcinogenesis. Thus, IL-6 emerges as a key player at all stages of pancreatic carcinogenesis and a potential therapeutic target.

Matched MeSH terms: Oxidative Stress/genetics
Fulltext Effect of dietary lead on intestinal nutrient transporters mRNA expression in broiler chickens

Ebrahimi R, Faseleh Jahromi M, Liang JB, Soleimani Farjam A, Shokryazdan P, Idrus Z

Biomed Res Int, 2015;2015:149745.
PMID: 25695048 DOI: 10.1155/2015/149745

Lead- (Pb-) induced oxidative stress is known to suppress growth performance and feed efficiency in broiler chickens. In an attempt to describe the specific underlying mechanisms of such phenomenon we carried out the current study. Ninety-six one-day-old broiler chicks were randomly assigned to 2 dietary treatment groups of 6 pen replicates, namely, (i) basal diet containing no lead supplement (control) and (ii) basal diet containing 200 mg lead acetate/kg of diet. Following 3 weeks of experimental period, jejunum samples were collected to examine the changes in gene expression of several nutrient transporters, antioxidant enzymes, and heat shock protein 70 (Hsp70) using quantitative real-time PCR. The results showed that addition of lead significantly decreased feed intake, body weight gain, and feed efficiency. Moreover, with the exception of GLUT5, the expression of all sugar, peptide, and amino acid transporters was significantly downregulated in the birds under Pb induced oxidative stress. Exposure to Pb also upregulated the antioxidant enzymes gene expression together with the downregulation of glutathione S-transferase and Hsp70. In conclusion, it appears that Pb-induced oxidative stress adversely suppresses feed efficiency and growth performance in chicken and the possible underlying mechanism for such phenomenon is downregulation of major nutrient transporter genes in small intestine.

Matched MeSH terms: Oxidative Stress/genetics
Fulltext Differential expression and role of hyperglycemia induced oxidative stress in epigenetic regulation of β1, β2 and β3-adrenergic receptors in retinal endothelial cells

Safi SZ, Qvist R, Yan GO, Ismail IS

BMC Med Genomics, 2014;7:29.
PMID: 24885710 DOI: 10.1186/1755-8794-7-29

Aberrant epigenetic profiles are concomitant with a spectrum of developmental defects and diseases. Role of methylation is an increasingly accepted factor in the pathophysiology of diabetes and its associated complications. This study aims to examine the correlation between oxidative stress and methylation of β1, β2 and β3-adrenergic receptors and to analyze the differential variability in the expression of these genes under hyperglycemic conditions.

Matched MeSH terms: Oxidative Stress/genetics*
Chlorella vulgaris modulates hydrogen peroxide-induced DNA damage and telomere shortening of human fibroblasts derived from different aged individuals

Makpol S, Yaacob N, Zainuddin A, Yusof YA, Ngah WZ

Afr J Tradit Complement Altern Med, 2009 Jul 03;6(4):560-72.
PMID: 20606778

The objective of this study was to investigate the modulatory effect of Chlorella vulgaris on cultured fibroblast cells derived from young and old aged individuals focusing on DNA damage, telomere length and telomerase activity. Dose-response test of the algal extract on cells in both age groups revealed that optimum viability was observed at a concentration of 50 microg/ml. Results obtained showed that Chlorella vulgaris exhibited protective effects against H(2)O(2)-induced oxidative stress as shown by the reduction in damaged DNA caused by H(2)O(2) treatment (p<0.05) in Chlorella vulgaris pre- and post-treated groups (p<0.05). Pre-treatment of Chlorella vulgaris resulted in a significant decrease in DNA damage suggesting a bioprotective effect against free radical attacks. A decline in DNA damage was observed in post-treated cells which proves Chlorella vulgaris to present bioremediative properties. In cells induced with oxidative stress, telomere length decreased significantly coupled with a concomitant decline of telomerase activity (p<0.05). However, these reductions were prevented with prior and post treatment of Chlorella vulgaris. Therefore, we concluded that Chlorella vulgaris exhibited bioprotective effects especially in cells obtained from young donor but were more bioremediative for cells obtained from old donor as indicated by DNA damage, telomere shortening and reduction in telomerase activity.

Matched MeSH terms: Oxidative Stress/genetics
Reactive oxygen species-induced alterations in H19-Igf2 methylation patterns, seminal plasma metabolites, and semen quality

Darbandi M, Darbandi S, Agarwal A, Baskaran S, Dutta S, Sengupta P, et al.

J Assist Reprod Genet, 2019 Feb;36(2):241-253.
PMID: 30382470 DOI: 10.1007/s10815-018-1350-y

PURPOSE: This study was conducted in order to investigate the effects of reactive oxygen species (ROS) levels on the seminal plasma (SP) metabolite milieu and sperm dysfunction.
METHODS: Semen specimens of 151 normozoospermic men were analyzed for ROS by chemiluminescence and classified according to seminal ROS levels [in relative light units (RLU)/s/106 sperm]: group 1 (n = 39): low (ROS

Matched MeSH terms: Oxidative Stress/genetics
Piper betle Induced Cytoprotective Genes and Proteins via the Nrf2/ARE Pathway in Aging Mice

Aliahmat NS, Abdul Sani NF, Wan Hasan WN, Makpol S, Wan Ngah WZ, Mohd Yusof YA

J Nutrigenet Nutrigenomics, 2016;9(5-6):243-253.
PMID: 28002828 DOI: 10.1159/000452407

BACKGROUND/AIMS: The objective of this study was to elucidate the underlying antioxidant mechanism of aqueous extract of Piper betle (PB) in aging rats. The nuclear factor erythroid 2-related factor 2 (Nrf2)/ARE pathway involving phase II detoxifying and antioxidant enzymes plays an important role in the antioxidant system by reducing electrophiles and reactive oxygen species through induction of phase II enzymes and proteins.
METHODS: Genes and proteins of phase II detoxifying antioxidant enzymes were analyzed by QuantiGenePlex 2.0 Assay and Western blot analysis.
RESULTS: PB significantly induced genes and proteins of phase II and antioxidant enzymes, NAD(P)H quinone oxidoreductase 1, and catalase in aging mice (p < 0.05). The expression of these enzymes were stimulated via translocation of Nrf2 into the nucleus, indicating the involvement of ARE, a cis-acting motif located in the promoter region of nearly all phase II genes.
CONCLUSIONS: PB was testified for the first time to induce cytoprotective genes through the Nrf2/ARE signaling pathway, thus unraveling the antioxidant mechanism of PB during the aging process.

Matched MeSH terms: Oxidative Stress/genetics
Fulltext Oxidative stress-induced chromosome breaks within the ABL gene: a model for chromosome rearrangement in nasopharyngeal carcinoma

Tan SN, Sim SP, Khoo AS

Hum Genomics, 2018 06 18;12(1):29.
PMID: 29914565 DOI: 10.1186/s40246-018-0160-8

BACKGROUND: The mechanism underlying chromosome rearrangement in nasopharyngeal carcinoma (NPC) remains elusive. It is known that most of the aetiological factors of NPC trigger oxidative stress. Oxidative stress is a potent apoptotic inducer. During apoptosis, chromatin cleavage and DNA fragmentation occur. However, cells may undergo DNA repair and survive apoptosis. Non-homologous end joining (NHEJ) pathway has been known as the primary DNA repair system in human cells. The NHEJ process may repair DNA ends without any homology, although region of microhomology (a few nucleotides) is usually utilised by this DNA repair system. Cells that evade apoptosis via erroneous DNA repair may carry chromosomal aberration. Apoptotic nuclease was found to be associated with nuclear matrix during apoptosis. Matrix association region/scaffold attachment region (MAR/SAR) is the binding site of the chromosomal DNA loop structure to the nuclear matrix. When apoptotic nuclease is associated with nuclear matrix during apoptosis, it potentially cleaves at MAR/SAR. Cells that survive apoptosis via compromised DNA repair may carry chromosome rearrangement contributing to NPC tumourigenesis. The Abelson murine leukaemia (ABL) gene at 9q34 was targeted in this study as 9q34 is a common region of loss in NPC. This study aimed to identify the chromosome breakages and/or rearrangements in the ABL gene in cells undergoing oxidative stress-induced apoptosis.
RESULTS: In the present study, in silico prediction of MAR/SAR was performed in the ABL gene. More than 80% of the predicted MAR/SAR sites are closely associated with previously reported patient breakpoint cluster regions (BCR). By using inverse polymerase chain reaction (IPCR), we demonstrated that hydrogen peroxide (H2O2)-induced apoptosis in normal nasopharyngeal epithelial and NPC cells led to chromosomal breakages within the ABL BCR that contains a MAR/SAR. Intriguingly, we detected two translocations in H2O2-treated cells. Region of microhomology was found at the translocation junctions. This observation is consistent with the operation of microhomology-mediated NHEJ.
CONCLUSIONS: Our findings suggested that oxidative stress-induced apoptosis may participate in chromosome rearrangements of NPC. A revised model for oxidative stress-induced apoptosis mediating chromosome rearrangement in NPC is proposed.

Matched MeSH terms: Oxidative Stress/genetics*

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