Oxidative stress alters mitochondrial bioenergetics and modifies pancreatic cell death independently of cyclophilin D, resulting in an apoptosis-to-necrosis shift.

ABSTRACT: Mitochondrial dysfunction lies at the core of acute pancreatitis (AP). Diverse AP stimuli induce Ca²⁺-dependent formation of the mitochondrial permeability transition pore (MPTP), a solute channel modulated by cyclophilin D (CypD), the formation of which causes ATP depletion and necrosis. Oxidative stress reportedly triggers MPTP formation and is elevated in clinical AP, but how reactive oxygen species influence cell death is unclear. Here, we assessed potential MPTP involvement in oxidant-induced effects on pancreatic acinar cell bioenergetics and fate. H₂O₂ application promoted acinar cell apoptosis at low concentrations (1-10 μm), whereas higher levels (0.5-1 mm) elicited rapid necrosis. H₂O₂ also decreased the mitochondrial NADH/FA

SUBMITTER: Armstrong JA 

PROVIDER: S-EPMC5971444 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature