Curcumin pretreatment protects against hypoxia/reoxgenation injury via improvement of mitochondrial function, destabilization of HIF-1α and activation of Epac1-Akt pathway in rat bone marrow mesenchymal stem cells

Publication date: January 2019Source: Biomedicine & Pharmacotherapy, Volume 109Author(s): Xujie Wang, Yijie Zhang, Yunshu Yang, Wei Zhang, Liang Luo, Fu Han, Hao Guan, Ke Tao, Dahai HuAbstractBone marrow mesenchymal stem cells (BMSCs) possess promising therapeutic effects and have been considered as a highly desirable agent for tissue injury treatment. However, little survived cells after transplanting due to severe relocated conditions (characterized by prolonged hypoxia and oxidative stress) lead to hampered benefits of BMSCs-based cell therapy. Curcumin, a natural dietary product, has attracted increasing attention owing to its profound pharmacologic properties. Here, we report the protective effects of curcumin pretreatment in BMSCs against hypoxia and reoxygenation (H/R) triggered injury, which mimick ischemia/reperfusion in vivo. We found that curcumin pretreatment remarkably inhibited H/R-induced cell viability loss, cell nuclei condensation, LDH leakage, as well as caspase-3 activity increase in BMSCs. Furthermore, curcumin pretreatment prevented H/R-induced mitochondrial dysfunction through expediting adenosine triphosphate production and suppressing reactive oxygen species accumulation and mitochondrial membrane potential decline. In addition, curcumin pretreatment notably induced HIF-1α destabilization, Epac1 and Akt activation, and Erk1/2 and p38 deactivation. However, Epac1 inhibitor ESI-09 obviously restrained the increase of p-Akt induced by curcumin, but not ...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research