Astaxanthin inhibits H2O2-mediated apoptotic cell death in mouse neural progenitor cells via modulation of P38 and MEK signaling pathways.
In the present study, 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-pretreated 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-GSK3beta, 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 ATP production ability of H2O2-treated cells. These findings indicate that astaxanthin inhibits H2O2-mediated apoptotic features in mNPCs. Inhibition assays with SB203580 (10 microM, a specific inhibitor of p38) and PD98059 (10 microM, a specific inhibitor of MEK) clearly showed that astaxanthin can inhibit H2O2-mediated apoptotic death via modulation of p38 and MEK signaling pathways.
Kim
Jeong-Hwan
JH
Department of Biomaterial Control,Dong-Eui University, Busan 614-714, Korea.
Choi
Woobong
W
Lee
Jong-Hwan
JH
Jeon
Sung-Jong
SJ
Choi
Yung-Hyun
YH
Kim
Byung-Woo
BW
Chang
Hyo-Ihl
HI
Nam
Soo-Wan
SW
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D018929:Cell Culture Techniques; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005419:Flavonoids / Q000008:administration & dosage; D006861:Hydrogen Peroxide / Q000008:administration & dosage*; D007093:Imidazoles / Q000008:administration & dosage; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D051379:Mice; D016877:Oxidants / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage; D015398:Signal Transduction / Q000187:drug effects*; D013116:Spinal Cord / Q000166:cytology*; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D024341:Xanthophylls / Q000008:administration & dosage; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D016877:Oxidants; D011725:Pyridines; D024341:Xanthophylls; D000255:Adenosine Triphosphate; C005948:astaxanthine; D006861:Hydrogen Peroxide; D048051:p38 Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one