The negative role of histone acetylation in cobalt chloride-induced neurodegenerative damages in SHSY5Y cells
Guo, Z; Tang, J; Wang, J; Zheng, F; Zhang, C; Wang, YL; Cai, P; Shao, W; Yu, G; Wu, S; Li, H
| HERO ID | 10043455 |
|---|---|
| In Press | No |
| Year | 2021 |
| Title | The negative role of histone acetylation in cobalt chloride-induced neurodegenerative damages in SHSY5Y cells |
| Authors | Guo, Z; Tang, J; Wang, J; Zheng, F; Zhang, C; Wang, YL; Cai, P; Shao, W; Yu, G; Wu, S; Li, H |
| Journal | Ecotoxicology and Environmental Safety |
| Volume | 209 |
| Page Numbers | 111832 |
| Abstract | Cobalt has been known for its neurotoxicity in numerous studies. However, the molecular mechanism underlying cobalt-induced neurotoxicity remains largely unknown. In this study, two neuroblastoma (SHSY5Y and N2a) cell lines and a phaeochromocytoma (PC12) line were used as in vitro models. Cells were treated for 24 h with 50, 100, 200, 300, 400 µM cobalt chloride (CoCl2) or cultured with 300 μM CoCl2 for 4, 8, 12 and 24 h to investigate the effects of histone acetylation on CoCl2-induced neurodegenerative damages. Our findings demonstrate that CoCl2 suppresses the acetylation of histone H3 and H4 in a time-dependent and dosage-dependent manner. Furthermore, CoCl2 selectively decreases the expression and activity of histone acetyltransferase (HAT) but has no effects on histone deacetylase (HDAC) in SHSY5Y cells. More importantly, we show that 100 ng/mL HDAC inhibitor trichostatin (TSA) pre-treatment partly attenuates 300 μM CoCl2-induced neurodegenerative damages in SHSY5Y cells. Mechanistic analyses show that CoCl2-induced neurodegenerative damages are associated with the dysfunction of APP, BACE1, PSEN1, NEP and HIF-1α genes, whose expression are partly mediated by histone modification. In summary, we demonstrate that histone acetylation is involved in CoCl2-induced neurodegenerative damages. Our study indicates an important connection between histone modification and the pathological process of neurodegenerative damages and provides a mechanism for cobalt-mediated epigenetic regulation. |
| Doi | 10.1016/j.ecoenv.2020.111832 |
| Pmid | 33383341 |
| Wosid | WOS:000611821600001 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |