Transcriptional regulation of Cidea, mitochondrial cell death-inducing DNA fragmentation factor α-like effector A, in mouse liver by peroxisome proliferator-activated receptor α and γ

Navin Viswakarma, Songtao Yu, Swati Naik, Papreddy Kashireddy, Kojiro Matsumoto, Joy Sarkar, Sailesh Surapureddi, Yuzhi Jia, Sambasiva Rao Musunuri, Janardan K Reddy*

*Corresponding author for this work

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Cidea (cell death-inducing DNA fragmentation factor α-like effector A), a member of a novel family of proapoptotic proteins, is expressed abundantly in the brown adipose tissue of the mouse. Although Cidea mRNA is not detectable in the mousel iver, we now show that peroxisome proliferator-activated receptor (PPAR) α ligands Wy-14,643 and ciprofibrate increase the Cidea mRNA level in a PPARα-dependent manner, whereas Cidea induction in liver by PPARγ overexpression is PPARα independent. Increase in Cidea mRNA content in liver did not alter the expression of uncoupling protein 1 (Ucp1) gene, which regulates thermogenesis, lipolysis, and conservation of energy. Although Cidea is considered to be a proapoptotic factor, Cidea induction in liver did not result in increased apoptosis. To elucidate the mechanism by which PPARα and PPARγ regulate Cidea gene expression in the liver, we analyzed the promoter region of the Cidea gene. Three putative peroxisome proliferator response elements (PPREs) are found in the Cidea gene promoter. Transactivation, gel-shift, and chromatin immunoprecipitation assays indicated that the proximal PPRE in Cidea gene (Cidea-PPRE1 at -680/-668) is functional for both PPARα and -γ. We conclude that Cidea is a novel target gene for both PPARα and -γ in the liver where these two transcription factors utilize the same PPRE region for dual regulation. The induction of Cidea in liver with these PPARα and -γ agonists suggests a possible role for Cidea in energy metabolism and a less likely role in hepatocyte apoptosis.

Original languageEnglish (US)
Pages (from-to)18613-18624
Number of pages12
JournalJournal of Biological Chemistry
Volume282
Issue number25
DOIs
StatePublished - Jun 22 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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