Delphinidin prevents hypoxia-induced mouse embryonic stem cell apoptosis through reduction of intracellular reactive oxygen species-mediated activation of JNK and NF-kappa B, and Akt inhibition

作者：Seo Bit Na; Ryu Jung Min; Yun Seung Pil; Jeon Ji Hoon; Park Su Shin; Oh Keon Bong; Park Jin Ki; Han Ho Jae^*

来源：Apoptosis, 2013, 18(7): 811-824.

DOI：10.1007/s10495-013-0838-2

• Delphinidin
• Apoptosis
• Hypoxia
• Embryonic stem cells

Delphinidin, gallic acid, betulinic acid, and ursolic acid, which are bio-active ingredients in a variety of fruits, vegetables, and herbs, have potent antioxidant activity and various biological activities. However, it is not clear whether these bio-active ingredients can significantly contribute to the protection of embryonic stem (ES) cells from hypoxia-induced apoptosis. In the present study, hypoxia-induced ES cells apoptosis with time, which were abrogated by pretreatment with all ingredients. Hypoxia-induced ROS generation was blocked by pretreatment with all ingredients in a dose-dependent manner, with the maximum ROS scavenging effect observed for delphinidin. Hypoxia increased phosphorylation of JNK and NF-kappa B were blocked by pretreatment of delphinidin as well as NAC. Hypoxia decreased phosphorylation of Akt(thr308) and (ser473); these decreases were reversed by pretreatment with delphinidin or NAC. However, Akt inhibition did not affect NF-kappa B phosphorylation. Delphinidin attenuated the hypoxia-induced increase in Bax, cleaved caspase-9, cleaved caspase-3, and decrease in Bcl-2, which were diminished by pretreatment of Akt inhibitor. Hypoxia induced Bax translocation from the cytosol to mitochondria. Furthermore, hypoxia induced mitochondria membrane potential loss and cytochrome c release in cytosol, which were blocked by delphinidin pretreatment. Hypoxia induced cleavage of procaspase-9 and procaspase-3 which were blocked by delphinidin or SP600125, but Akt inhibitor abolished the protection effect of delphinidin. Moreover, inhibition of JNK and NF-kappa B abolished hypoxia-induced ES cell apoptosis and inhibition of Akt attenuated delphinidin-induced blockage of apoptosis. The results indicate that delphinidin can prevent hypoxia-induced apoptosis of ES cells through the inhibition of JNK and NF-kappa B phosphorylation, and restoration of Akt phosphorylation.

• 出版日期2013-7