Astaxanthin Inhibits H2O2-Mediated Apoptotic Cell Death in Mouse Neural Progenitor Cells via Modulation of P38 and MEK Signaling Pathways

In the present study, the neuroprotective effects of astaxanthin on H2O2-mediated apoptotic cell death, using cultured mouse neural progenitor cells (mNPCs), were investigated. To cause apoptotic cell death, mNPCs were pretreated with astaxanthin for 8 h and followed by treatment of 0.3 mM H2O2. Pretreatment of mNPCs with astaxanthin significantly inhibited H2O2-mediated apoptosis and induced cell growth in a dose-dependent manner. In Western blot analysis, astaxanthin-p retreated cells showed the activation of p-Akt, p-MEK, p-ERK, and Bcl-2, and the reduction of p-P38, p-SAPK/JNK, Bax, p-GSK3b, cytochrome c, caspase-3, and PARP. Because H2O2 triggers caspases activation, this study examined whether astaxanthin can inhibit caspases activation in H2O2-treated mNPCs. After H2O2 treatment, caspases activities were prominently increased, but astaxanthin pretreatment significantly inhibited H2O2-mediated caspases; activation. Astaxanthin pretreatment also significantly recovered the ATP production ability of H2O2-treated cells. These findings indicate that astaxanthin inhibits H(2)O(2-)mediated apoptotic features in mNPCs. Inhibition assays with SB203580 (10 mu M, a specific inhibitor of p38) and PD98059 (10 mu M, a specific inhibitor of MEK) clearly showed that astaxanthin can inhibit H2O2-mediated apoptotic death via modulation of p38 and MEK signaling pathways.