The negative role of histone acetylation in cobalt chloride-induced neurodegenerative damages in SHSY5Y cells

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 mu M cobalt chloride (CoCl2) or cultured with 300 mu M 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 mu M 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-1 alpha 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.

Automated summary

Cobalt-induced neurotoxicity is associated with the inhibition of histone acetylation, leading to dysfunction of key genes associated with neurodegenerative damages. Pre-treatment with HDAC inhibitor can partially attenuate the neurodegenerative damages induced by CoCl2 in SHSY5Y cells. This study provides insights into the connection between histone modification and cobalt-induced neurodegenerative damages.