Expression of peroxisome proliferator-activated receptors (PPARs) in human astrocytic cells: PPARγ agonists as inducers of apoptosis

Naibedya Chattopadhyay, Dhirendra P. Singh, Oliver Heese, Madan M. Godbole, Toshimichi Sinohara, Peter M. Black, Edward M. Brown

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

We report the isolation by RT-PCR of partial cDNAs encoding the human peroxisome proliferator-activated receptor (PPAR) isoforms PPARβ and -γ in human primary astrocytes (HPA) as well as in the human malignant astrocytoma cell line T98G. In contrast, we failed to detect PPARα mRNA in either of these two cell types. Because PPARβ is ubiquitously expressed but has, as yet, no known function, we pursued our functional studies of these cells with regard to PPARγ. To that end, we showed that PPARγ protein is abundantly expressed in both cell types, having a molecular weight of approximately 50 kDa. Immunocytochemistry revealed a predominantly nuclear localization of this receptor. Moreover, incubation of the two cell types with 1-12 μM 15- deoxy PGJ2 or 1-12 μM ciglitazone, both of which are agonists of PPARγ, induced loss of cellular viability as assessed by the MTT assay after a 4 hr incubation. Reduced cellular viability as a consequence of exposure to PGJ2 or ciglitazone resulted from induction of apoptosis, as assessed by DNA fragmentation and Hoechst staining, and involves activation of the CPP32 (caspase-3) protease. These data show that modulation of the process of apoptosis is one function of PPARγ in cells derived from the human astrocytic lineage. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)67-74
Number of pages8
JournalJournal of Neuroscience Research
Volume61
Issue number1
DOIs
StatePublished - Jul 1 2000

Keywords

  • Astrocytes
  • Astrocytoma
  • Cell death
  • Peroxisome

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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