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Histone acetylation plays an important role in MC-LR-induced apoptosis and cycle disorder in SD rat testicular cells
- Source :
- Chemosphere. 241:125073
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Microcystin-leucine arginine (MC-LR) is a variant of microcystins (MCs), which poses a serious threat to the reproductive system. Histone acetylation modification can regulate the expressions of apoptosis-related genes. However the mechanisms of histone acetylation involving MC-LR-induced apoptosis were not understood. This study investigated the change of histone acetylation and its role in apoptosis and cell cycle arrest induced by MC-LR. MC-LR enhanced the activity of histone deacetylase (HDAC), decreased the activity of histone acetylase (HAT), up-regulated the expression of HDAC1, and down-regulated the expressions of Ac-H3 and Ac-H4 in vitro and vivo. Meanwhile, MC-LR induced testicular tissue injury and increased the expressions of apoptosis-related genes, such as Bax, Caspase3 and Caspase8, ultimately causing cells apoptosis in testicular tissues. Furthermore, MC-LR also induced cell cycle arrest in S phase, increased the expression of P21Wif1/Cip1, and inhibited the expressions of cyclinD1, cyclinE1, CDK2 and E2F1. Importantly, HDAC inhibitor Trichostatin A (TSA) could ameliorate MC-LR-induced apoptosis and cell cycle arrest by reverse-regulating the expressions of these proteins. These results indicated that MC-LR could activate the mitochondrial apoptotic pathway and disorder the cell cycle pathway to induce the cell apoptosis by enhancing HDAC activity and reducing histone acetylation of normal testicular cells in SD rats. Hence, histone acetylation has a vital function in MC-LR-induced apoptosis in SD rat testicular cells, which provides a new insight on the reproductive toxicity of male induced by MC-LR.
- Subjects :
- Male
Environmental Engineering
Cell cycle checkpoint
Microcystins
Health, Toxicology and Mutagenesis
0208 environmental biotechnology
Apoptosis
02 engineering and technology
010501 environmental sciences
Arginine
Hydroxamic Acids
01 natural sciences
Histones
Rats, Sprague-Dawley
Testis
medicine
Animals
Humans
Environmental Chemistry
E2F1
0105 earth and related environmental sciences
biology
Chemistry
Reproduction
Cell Cycle
Public Health, Environmental and Occupational Health
Acetylation
General Medicine
General Chemistry
Cell cycle
Pollution
HDAC1
Rats
020801 environmental engineering
Cell biology
Trichostatin A
Histone
biology.protein
Histone deacetylase
medicine.drug
Subjects
Details
- ISSN :
- 00456535
- Volume :
- 241
- Database :
- OpenAIRE
- Journal :
- Chemosphere
- Accession number :
- edsair.doi.dedup.....d8d32505a403d6f4b69562c77d4d5e02