4.7 Article

Histone acetylation plays an important role in MC-LR-induced apoptosis and cycle disorder in SD rat testicular cells

Journal

CHEMOSPHERE
Volume 241, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.chemosphere.2019.125073

Keywords

Microcystin-leucine arginine (MC-LR); Trichostatin A (TSA); Histone deacetylase (HDAC); Histone acetylation; Apoptosis; Cell cycle arrest

Funding

  1. National Nature Science Foundation of China [81472948, 81773384]
  2. Henan natural science foundation [162300410267]

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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 Box, 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 P21(Wif1/Cip1) and inhibited the expressions of cyclinD1, cyclinEl, 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. (C)2019 Elsevier Ltd. All rights reserved.

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