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

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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-γ 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-γ antagonist GW9662, indicating that PPAR-γ functions as the mediator of the apoptotic effect of DHA. Furthermore, our result showed that DHA induces the PPAR-γ 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-γ-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-γ-p53, in mediating the apoptotic effect of DHA in Reh cells.

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Acknowledgments

We are grateful to Professor Heidi Keil Blomhoff, Department of Biochemistry, Institute Group of Basic Medical Sciences, University of Oslo-Norway for allowing us to carry out most of this work in her laboratory. We also thank Dr Biserka Relic, Department of Rheumatology, University of Liege, Belgium for providing the PPAR-γ antibody.

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Authors and Affiliations

  1. Faculty of Medicine, Department of Biochemistry, Tabriz Medical Sciences University, Tabriz, Iran

    Hamid Zand & Ali Rhimipour

  2. Cellular and Molecular Biology Research Center, Iran University Medical Sciences, Tehran, Iran

    Masoomeh Bakhshayesh, Mohammad Shafiee, Issa Nour Mohammadi & Saideh Salimi

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  1. Hamid Zand
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  2. Ali Rhimipour
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  3. Masoomeh Bakhshayesh
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Correspondence to Hamid Zand.

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Zand, H., Rhimipour, A., Bakhshayesh, M. et al. Involvement of PPAR-γ and p53 in DHA-induced apoptosis in Reh cells. Mol Cell Biochem 304, 71–77 (2007). https://doi.org/10.1007/s11010-007-9487-5

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  • DOI: https://doi.org/10.1007/s11010-007-9487-5

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