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PMID: 17487454 Published · ppublish English Journal Article

Involvement of PPAR-gamma and p53 in DHA-induced apoptosis in Reh cells.

Molecular and cellular biochemistry ·Vol. 304 ·No. 1-2 ·2007-10-00 ·Pages 71-7

Zand H, Rhimipour A, Bakhshayesh M, Shafiee M, Nour Mohammadi I, Salimi S

Abstract

Docosahexaenoeic acid (DHA, 22:6 n-3) is an omega-3 polyunsaturated fatty acid that is found in fish oil and exerts cytotoxic effect on a variety of cell lines. The molecular target, responsible for mediating this effect of DHA, still remains unknown. In this report, we presented experimental evidences for the role of PPAR-gamma in conveying the cytotoxic effect of DHA. We showed that DHA induces apoptosis in Reh and Ramos cells and apoptotic effect of DHA is inhibited by the PPAR-gamma antagonist GW9662, indicating that PPAR-gamma functions as the mediator of the apoptotic effect of DHA. Furthermore, our result showed that DHA induces the PPAR-gamma protein levels in both Reh and Ramos cells. Interestingly, DHA was found to induce the expression of p53 protein in Reh cells in a PPAR-gamma-dependent manner. The up-regulation of p53 protein by DHA kinetically correlated with the activation of caspase 9, caspase 3, and induction of apoptosis, suggesting a role for p53 in DHA-mediated apoptosis in Reh cells. Taken together, these findings suggest a new signaling pathway, DHA-PPAR-gamma-p53, in mediating the apoptotic effect of DHA in Reh cells.

MeSH Terms
Apoptosis/drug effects Caspase 3/metabolism Caspase 9/metabolism Cell Line Cytotoxins/pharmacology Docosahexaenoic Acids/pharmacology Gene Expression Regulation/drug effects Humans PPAR gamma/genetics,metabolism,physiology Poly(ADP-ribose) Polymerases/metabolism Tumor Suppressor Protein p53/physiology
Chemicals
Cytotoxins PPAR gamma Tumor Suppressor Protein p53 Docosahexaenoic Acids Poly(ADP-ribose) Polymerases Caspase 3 Caspase 9
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Zand Hamid
Faculty of Medicine, Department of Biochemistry, Tabriz Medical Sciences University, Tabriz, Iran. [email protected]
Rhimipour Ali
Bakhshayesh Masoomeh
Shafiee Mohammad
Nour Mohammadi Issa
Salimi Saideh
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Article Info
Journal
Molecular and cellular biochemistry
Abbr.
Mol Cell Biochem
ISSN
0300-8177
DOI
10.1007/s11010-007-9487-5
Email
[email protected]
Published
2007-10-00
Epub
2007-00-09
Pages
71-7
Language
English
Region
Netherlands
NLM ID
0364456
Subset
IM
External Links
PubMed source DOI: 10.1007/s11010-007-9487-5 View journal details
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