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Mitochondrial outer membrane voltage-dependent anion channel is involved in renal dysfunction in a spontaneously hypertensive rat carrying transfer RNA mutations.

Abstract：

:Mitochondrial DNA mutations promote hypertensive renal dysfunction, but the molecular mechanism remains unclear. This study compared renal damage between spontaneously hypertensive rats (SHR) and SHR with mitochondrial transfer (t)RNA mutations. To investigate the role of mitochondrial outer membrane voltage-dependent anion channel 1 (VDAC1) in the process of tRNA-promoting mitochondrial dysfunction, we treated HK-2 cells with H2O2, cyclosporine (CsA), or atractylodin (Atr) to observe the association between VDAC1 and mitochondrial function. Intriguingly, the mitochondrial structure of SHR carrying tRNA mutations was obviously disordered, and reactive oxygen species production and VDAC1 and Bax expression and binding were increased, which was associated with marked renal dysfunction. The expression of VDAC1 and Bax was also up-regulated in HK-2 cells by H2O2 treatment. However, CsA and Atr had no significant effect on the expression of VDAC1 and Bax. H2O2 caused mitochondrial membrane potential collapse, while CsA could increase the mitochondrial membrane potential and Atr had the opposite effect. Treatment with H2O2 significantly decreased ATP synthesis, which was improved by intervention with Atr. H2O2 also decreased the maximum oxygen consumption rate, while CsA and Atr had no significant effect. We found that H2O2 promoted the colocalization of VDAC1 and Bax, which was partially inhibited by intervention with CsA or Atr. In conclusion, we found that tRNA mutations promoted hypertensive renal insufficiency. Increased reactive oxygen species was an important associated mechanism, which inhibited mitochondrial function by affecting VDAC1 expression and function.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Zhu C,Tian L,Yang H,Chen P,Li Y,Liu Y

doi

10.1016/j.ejphar.2019.172622

subject

Has Abstract

pub_date

2019-12-15 00:00:00

pages

172622

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(19)30574-6

journal_volume

865

pub_type

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Mitochondrial outer membrane voltage-dependent anion channel is involved in renal dysfunction in a spontaneously hypertensive rat carrying transfer RNA mutations.