Synergistic effect of cAMP and palmitate in promoting altered mitochondrial function and cell death in HepG2 cells

Linxia Zhang, Linsey Christine Seitz, Amy M. Abramczyk, Christina Chan*

*Corresponding author for this work

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Saturated free fatty acids (FFAs), e.g. palmitate, have long been shown to induce toxicity and cell death in various types of cells. In this study, we demonstrate that cAMP synergistically amplifies the effect of palmitate on the induction of cell death in human hepatocellular carcinoma cell line, HepG2 cells. Elevation of cAMP level in palmitate-treated cells led to enhanced mitochondrial fragmentation, mitochondrial reactive oxygen species (ROS) generation and mitochondrial biogenesis. Mitochondrial fragmentation precedes mitochondrial ROS generation and mitochondrial biogenesis, and may contribute to mitochondrial ROS overproduction and subsequent mitochondrial biogenesis. Fragmentation of mitochondria also facilitated the release of cytotoxic mitochondrial proteins, such as Smac, from the mitochondria and subsequent activation of caspases. However, cell death induced by palmitate and cAMP was caspase-independent and mainly necrotic.

Original languageEnglish (US)
Pages (from-to)716-727
Number of pages12
JournalExperimental Cell Research
Volume316
Issue number5
DOIs
StatePublished - Mar 10 2010

Keywords

  • Apoptosis
  • Mitochondria
  • Necrosis
  • Palmitate
  • cAMP

ASJC Scopus subject areas

  • Cell Biology

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