Effects of Resveratrol and trans-3,5,4'-Trimethoxystilbene on Glutamate-Induced Cytotoxicity, Heme Oxygenase-1, and Sirtuin 1 in HT22 Neuronal Cells

  • Kim, Dae-Won (Department of Neurosurgery, Wonkwang University School of Medicine) ;
  • Kim, Young-Mi (Department of Microbiology and Immunology, Wonkwang University School of Medicine) ;
  • Kang, Sung-Don (Department of Neurosurgery, Wonkwang University School of Medicine) ;
  • Han, Young-Min (Department of Radiology, Chonbuk National University Hospital & Medical School) ;
  • Pae, Hyun-Ock (Department of Microbiology and Immunology, Wonkwang University School of Medicine)
  • Received : 2012.02.27
  • Accepted : 2012.04.25
  • Published : 2012.05.31


Resveratrol (trans-3,5,4'-trihydroxystilbene) has received considerable attention recently for the potential neuroprotective effects in neurodegenerative disorders where heme oxygenase-1 (HO-1) and sirtuin 1 (SIRT1) represent promising therapeutic targets. Resveratrol has been known to increase HO-1 expression and SIRT1 activity. In this study, the effects of resveratrol and trans-3,5,4'-trimethoxystilbene (TMS), a resveratrol derivative, on cytotoxicity caused by glutamate-induced oxidative stress, HO-1 expression, and SIRT1 activation have been investigated by using murine hippocampal HT22 cells, which have been widely used as an in vitro model for investigating glutamate-induced neurotoxicity. Resveratrol protected HT22 neuronal cells from glutamate-induced cytotoxicity and increased HO-1 expression as well as SIRT1 activity in a concentration-dependent manner. Cytoprotection afforded by resveratrol was partially reversed by the specific inhibition of HO-1 expression by HO-1 small interfering RNA and the nonspecific blockage of HO-1 activity by tin protoporphyrin IX, but not by SIRT1 inhibitors. Surprisingly, TMS, a resveratrol derivative with methoxyl groups in lieu of the hydroxyl groups, and trans-stilbene, a non-hydroxylated analog, failed to protect HT22 cells from glutamate-induced cytotoxicity and to increase HO-1 expression and SIRT1 activity. Taken together, our findings suggest that the cytoprotective effect of resveratrol was at least in part associated with HO-1 expression but not with SIRT1 activation and, importantly, that the presence of hydroxyl groups on the benzene rings of resveratrol appears to be necessary for cytoprotection against glutamate-induced oxidative stress, HO-1 expression, and SIRT1 activation in HT22 neuronal cells.


Supported by : National Research Foundation of Korea (NRF)


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