Mitochondria-dependent apoptosis in triptolide-induced hepatotoxicity is associated with the Drp1 activation.

Abstract:

:How triptolide is associated with mitochondrial dysfunction and apoptosis in connection with its hepatotoxicity remains unclear. The objective of our study was to find out the link between mitochondrial dynamics and cell death in triptolide induced hepatotoxicity. We treated L02 cells with 25 nM concentration of triptolide. The results demonstrated that triptolide treatment caused an increase in apoptotic cell death, mitochondrial depolarization, ROS overproduction, a decrease in ATP production, and mitochondrial fragmentation which in turn is associated with the activation of Drp1 fission protein. Triptolide treatment led to the translocation of Drp1 from the cytosol into outer mitochondrial membrane where it started mitochondrial fission. This fission event is coupled with the mitochondrial release of cytochrome c into the cytosol and subsequently caspase-3 activation. TEM analysis of rat liver tissues revealed the distortion of mitochondrial morphology in triptolide-treated group. Western blot analysis explained that disruption in mitochondrial morphology was attached with the recruitment of Drp1 to mitochondria, cytochrome c release, and caspase-3 activation. However, Mdivi-1 co-treatment inhibited the activation of Drp1 and caspase-3 and blocked the release of cytochrome c into the cytosol. In short, inhibiting Drp1 protein activation may provide a new potential target for curing Drp1-associated apoptosis in triptolide-induced hepatotoxicity.

journal_name

Toxicol Mech Methods

authors

Hasnat M,Yuan Z,Ullah A,Naveed M,Raza F,Baig MMFA,Khan A,Xu D,Su Y,Sun L,Zhang L,Jiang Z

doi

10.1080/15376516.2019.1669247

subject

Has Abstract

pub_date

2020-02-01 00:00:00

pages

124-133

issue

2

eissn

1537-6516

issn

1537-6524

journal_volume

30

pub_type

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