Involvement of PPAR-gamma and p53 in DHA-induced apoptosis in Reh cells.
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.
Zand
Hamid
H
Faculty of Medicine, Department of Biochemistry, Tabriz Medical Sciences University, Tabriz, Iran. hamid.zand@medisin.uio.no
Rhimipour
Ali
A
Bakhshayesh
Masoomeh
M
Shafiee
Mohammad
M
Nour Mohammadi
Issa
I
Salimi
Saideh
S
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D003603:Cytotoxins / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D003603:Cytotoxins; D047495:PPAR gamma; D016159:Tumor Suppressor Protein p53; D004281:Docosahexaenoic Acids; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053453:Caspase 9