Kim, Youn-Jung Kim, Young-Seok Kim, Mi-Soon Ryu, Jae-Chun 2024-01-21T01:02:57Z 2024-01-21T01:02:57Z 2021-09-02 2007-05-05 0300-483X https://pubs.kist.re.kr/handle/201004/134398 Methylmercury (MeHg) is a ubiquitous environmental toxicant and shows neurotoxicity to central nerve system (CNS) or neuronal cells. It has been known that MeHg has more influence to developing or differentiating CNS/neuronal cells than adult or differentiated CNS/neuronal cells. This study examined the effect of MeHg on differentiation of human neuroblastoma SH-SY5Y cells induced by all-trans-retinoic acid (RA). MeHg caused the impairment of the RA-induced G(1/0) phase arrest; it was induced the reduction of G(1/0) phase and S phase arrest. Extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase C (PKC) are involved in the RA-mediated differentiation and cell cycle progression. Activation of ERK1/2 by RA was increased more in MeHg-treated differentiating cells, comparing with only RA-treated groups. Furthermore, in both cases of inhibition of ERK1/2 with PD98059 or inhibition of PKC with GF109203X, RA/MeHg-induced ERK1/2 phosphorylation was reduced and G(1/0) phase arrest was induced. Thus, it indicates that the neuronal differentiation with RA was mediated by the ERK1/2 and PKC related pathway and MeHg resulted in neurotoxic influences through the disturbance in steps of differentiation by this pathway. These results suggest that MeHg inhibits RA-induced differentiation in SH-SY5Y cells by a pathway dependent ERK1/2 and PKC. (C) 2007 Elsevier Ireland Ltd. All rights reserved. English ELSEVIER IRELAND LTD PROTEIN-KINASE-C NEURITE OUTGROWTH MAP KINASE RETINOIC ACID SUSTAINED ACTIVATION NERVOUS-SYSTEM GROWTH-FACTOR HEAVY-METALS PC12 CELLS IN-VITRO The inhibitory mechanism of methylmercury on differentiation of human neuroblastorna cells Article 10.1016/j.tox.2007.01.003 1 TOXICOLOGY, v.234, no.1-2, pp.1 - 9 TOXICOLOGY 234 1-2 1 9 scie scopus 000246275800001 2-s2.0-34047132151 Pharmacology & Pharmacy Toxicology Pharmacology & Pharmacy Toxicology Article PROTEIN-KINASE-C NEURITE OUTGROWTH MAP KINASE RETINOIC ACID SUSTAINED ACTIVATION NERVOUS-SYSTEM GROWTH-FACTOR HEAVY-METALS PC12 CELLS IN-VITRO methylmercury differentiation cell cycle retinoic acid ERK PKC