CypD deficiency confers neuroprotection against mitochondrial abnormality caused by lead in SH-SY5Y cell.
Toxicol Lett
; 323: 25-34, 2020 May 01.
Article
em En
| MEDLINE
| ID: mdl-31874198
Mitochondrial permeability transition (MPT), which is mainly regulated by cyclophilin D (CypD) encoded by ppif gene, is an early event that occurs during mitochondrial stimuli exposure. Lead (Pb) induces MPT and subsequently causes mitochondrial abnormality, followed by events, including oxidative stress and cell death. Here, we generated a ppif-/- SH-SY5Y cell line to determine the role of CypD in Pb-induced mitochondrial abnormality. CypD deficiency significantly blocked mitochondrial permeability transition pore (MPTP) opening and inhibited mitochondrial membrane potential (MMP) collapse, as well as mitochondrial structure damage and fragmentation caused by Pb. Mitochondria fragmentation and MMP collapse, accompanying with Pb-induced downregulation of Glut1 and Glut3 and inactivation of AMPK signaling pathway, could impair the energy supply in wildtype cells. Meanwhile, ppif knockout can alleviate these impairments and maintain the energy supply. In addition, reactive oxygen species accumulation and cell death caused by Pb can also be attenuated by ppif knockout, thereby promoting cell survival. Our study tends to identify CypD as an important contributor to Pb-induced mitochondrial abnormality and provides a potential strategy to inhibit Pb neurotoxicity.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neuroproteção
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Peptidil-Prolil Isomerase F
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Chumbo
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Mitocôndrias
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article