title: Transcriptional regulation of Cidea, mitochondrial cell death-inducing DNA fragmentation factor alpha-like effector A, in mouse liver by peroxisome proliferator-activated receptor alpha and gamma.
abstract: Cidea (cell death-inducing DNA fragmentation factor alpha-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 mouse liver, we now show that peroxisome proliferator-activated receptor (PPAR) alpha ligands Wy-14,643 and ciprofibrate increase the Cidea mRNA level in a PPARalpha-dependent manner, whereas Cidea induction in liver by PPARgamma overexpression is PPARalpha 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 PPARalpha and PPARgamma 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 PPARalpha and -gamma. We conclude that Cidea is a novel target gene for both PPARalpha and -gamma in the liver where these two transcription factors utilize the same PPRE region for dual regulation. The induction of Cidea in liver with these PPARalpha and -gamma agonists suggests a possible role for Cidea in energy metabolism and a less likely role in hepatocyte apoptosis.
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611-3008.
authors.forename: Navin
authors.initials: N
authors.lastname: Viswakarma
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611-3008.
authors.forename: Songtao
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611-3008.
authors.forename: Swati
authors.initials: S
authors.lastname: Naik
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611-3008.
authors.forename: Papreddy
authors.initials: P
authors.lastname: Kashireddy
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611-3008.
authors.forename: Kojiro
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611-3008.
authors.forename: Joy
authors.initials: J
authors.lastname: Sarkar
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611-3008.
authors.forename: Sailesh
authors.initials: S
authors.lastname: Surapureddi
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611-3008.
authors.forename: Yuzhi
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611-3008.
authors.forename: M Sambasiva
authors.initials: MS
authors.lastname: Rao
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611-3008. Electronic address: jkreddy@northwestern.edu.
authors.forename: Janardan K
authors.initials: JK
authors.lastname: Reddy
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism / Q000502:physiology*; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D047493:PPAR alpha / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D051017:Apoptosis Regulatory Proteins; C112510:Cidea protein, mouse; D047493:PPAR alpha; D047495:PPAR gamma