![]() ![]() Following exposure to CpPLC, a significant generation of mitochondrial reactive oxygen species was observed, which coincided with the changes in the expression of vital components of MAP/ERK/RTK signaling cascade that regulates the downstream cellular functions. The present study was designed to understand the role of CpPLC in inducing survival mechanisms and mitochondrial-induced epigenetic changes in a human lymphocyte cell culture model. A major virulence factor during its infection is the enzyme phospholipase C encoded by the plc gene, known as Clostridium perfringens phospholipase C (CpPLC). Altogether, our observations provide vital molecular insights of the integrated mitoepigenetic signalling network in the airborne PM exposed individuals, hitherto unreported.Ĭlostridium perfringens, a rod-shaped, gram-positive, anaerobic, spore-forming bacterium is one of the most widely occurring bacterial pathogens, associated with a spectrum of diseases in humans. ![]() This impaired mtDNA methylation profile further correlated with the disturbed activity of electron chain complexes and expression of the mitochondria function genes in the high-risk group. Moreover, these changes were accompanied by the disturbances in the expression of TET genes and levels of mtDNA methylation. Importantly, we also observed higher expression levels of mitochondrial transcription factor TFAM, a key regulator of mtDNA replication and transcription in the high-risk group. The high-risk group reported significant alterations in the mtDNA copy number and expression of mitochondrial fission and fusion genes. These disturbances in the mitochondrial genome were further found to be associated with the vital processes of mitochondrial biogenesis. In addition, the upregulated expression levels of OMA1, DELE1, and HRI genes in the high-risk group confirmed the onset of an integrated stress response. The results of our pilot study showed that in comparison to the low-risk group, the levels of mitochondrial stress and oxidative DNA damage were significantly higher in the high-risk group. Different parameters related to oxidative DNA damage and repair, integrated stress response, mito-nuclear crosstalk, mitochondrial biogenesis, functioning and epigenetic machinery were assessed. Based on the place of residence and amount of PM exposure, the study groups were divided into high-risk group and low-risk group. We envisage that understanding the interplay between environmental toxin-induced signaling and predisposition to testicular cancers would spur identification of meaningful targets for useful therapeutic translational modalities.Īirborne particulate matter (PM) is known to be associated with various chronic human ailments, however, precise underlying molecular mechanisms remains elusive. Our results demonstrate that MIC in the form of N-succinimidyl N-methylcarbamate promotes germ-line genomic instability in vitro. ![]() This was accompanied by evidence of a deregulation of cell cycle progression, such as substantial fold-changes in the expression of proliferating cell nuclear antigen, Cyclin D1, Bcl-2 and Bax genes and aberrant expression of p53, cyclin A, cyclin E, CDK-2 and aurora kinase-B proteins. Chromosomal aberrations, telomere anomaly, aneuploidy and variable amplification of microsatellite repeats additionally indicated induced genomic instability. Treated cells also displayed elevated levels of inflammatory cytokines as well as morphological transformation and stress-responsive senescence. DNA damage, oxidative stress and apoptosis response parameters increased with time of exposure and dose after treatment. The investigations were performed in the cultured mouse spermatogonial GC-1 spg cell line using N-succinimidyl N-methylcarbamate, a surrogate chemical to MIC. The present study was performed to find out the pathophysiological implications of isocyanate exposure on the male germ line. Isocyanates, such as methyl isocyanate (MIC), with their wide industrial applications, are known to exert severe ill health effects. ![]() Male reproductive health is exquisitely sensitive to environmental insults as evidenced by the rising incidence of testicular cancers and low and probably declining semen quality. ![]()
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