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Abstrato

Protective Effect of S-Adenosyl-L-Methionine on Oxidative Stress-Induced Apoptosis Regulates Nrf2 via IGF-I in Rat Bone Marrow Mesenchymal Stem Cells

Myung-Hoon Oh, Jong-Hoon Kim and Chang-Won Kang

Bone marrow mesenchymal stem cell (MSC)-mediated regeneration is a promising treatment for degenerative diseases and traumatic injuries. S-Adenosyl-L-methionine (SAM) is the principal biological methyl donor. We hypothesized that the cytoprotective effect of SAM on oxidative stress-induced apoptosis in rat MSCs is due to insulin-like growth factor-I (IGF-I) and nuclear factor erythroid 2-related factor 2 (Nrf2). SAM (10 μM) increased both endogenous IGF-I levels and cell viability (p<0.05). In MSCs, 1 mM H2O2 at 6 h significantly decreased cell viability and IGF-I and Nrf2 activation, but increased ROS generation (p<0.05 and p<0.01, respectively). The decrease in cell viability, endogenous IGF-1, and Nrf2 in H2O2-induced apoptosis was recovered by SAM (10 μM). Apoptosis induced by H2O2 also decreased Nrf2 activity, as determined by immunofluorescence staining, but the decrease was also recovered by SAM. We demonstrated that H2O2-induced apoptosis was reduced by SAM through Annexin-V. Using a specific small interfering RNA (siRNA), the increase in SAM-induced cell viability and endogenous Nrf2 in the presence of H2O2 was suppressed by IGF-I siRNA, but the endogenous IGF-I level was not changed by Nrf2 siRNA. The increase in endogenous Nrf2 with exogenous IGF-I and H2O2 treatment was also suppressed by Nrf2 siRNA, but the IGF-I level was not inhibited (p<0.05). These results suggest that the cytoprotective effect of SAM against H2O2- induced apoptosis is mediated by increased Nrf2 activity through IGF-I. These factors could regulate the metabolic fate and survival of MSCs