Berberine Protects Mesenchymal Stem Cells against Hypoxia-Induced Apoptosis in Vitro

Abstract

Bone marrow mesenchymal stem cells (MSCs) have the potential to be used in the cellular therapy of solid organs. However, tissue regeneration is limited by the death of transplanted cells. One of the main mechanisms of stem cell death in transplanted organs is through ischemia. In the present study, we sought to investigate whether a plant-derived antioxidant, berberine (BBR), could protect MSCs against MSCs apoptosis in a model of ischemia consisting of serum deprivation-and hypoxia-induced apoptosis in vitro. We also investigated the potential mechanism(s) that may mediate the action of berberine. We found that berberine significantly attenuated hypoxia-induced MSC apoptosis. Further study revealed that berberine could scavenger the reactive oxygen species (ROS), inhibit the c-jun NH(2)-terminal kinase (JNK), the loss of mitochondrial membrane potential and the release of cytochrome c (Cyt C) and caspase-3. In addition, we also showed that berberine could activate phosphoinositide-3 kinase (PI3K)/Akt and that pretreatment with PI3K/Akt inhibitors prevented berberineinduced inhibition of ROS, JNK and subsequent apoptosis, suggesting that the protective effects of berberine were PI3K/Akt-dependent. Taken together, these findings reveal that berberine protects against MSC apoptosis by preventing ROS-dependent and JNK-driven cell apoptosis in a PI3K/Akt-dependent manner. These data indicate that berberine is a promising anti-apoptotic agent for improving MSC survival during cell transplantation.

Berberine Improved Aldo-Induced Podocyte Injury via Inhibiting Oxidative Stress and Endoplasmic Reticulum Stress Pathways both In Vivo and In Vitro

“…Although we did not detect the SR expression in our experiments, a previous study has proven that berberine could induce SR-A expression in macrophages [43]. Additionally, berberine could scavenge the reactive oxygen species (ROS) and inhibit the c-jun NH (2)-terminal kinase (JNK), the loss of mitochondrial membrane potential and the release of cytochrome c (Cyt C) and caspase-3 [44]. In our study, Aldo-treated rats showed a high glomerular ROS production marker (Fig.…”

Response of Adipose Tissue-Derived Stromal Cells in Tissue-Related O₂ Microenvironment to Short-Term Hypoxic Stress

“…A decrease in activity of the antioxidant enzyme catalase, a major metaboliser of ROS, without changes in SOD and SOD subunit levels confirmed that the metabolism of ROS was also impaired (or at least not sufficient) [Peterson et al, 2011]. Furthermore, short hypoxic exposure of ambient O 2 -expanded MSCs provoked a decrease in the mitochondrial transmembrane potential [Zhu et al, 2006;Zhang et al, 2009;Nie et al, 2011], cytochrome C release into the cytoplasm [Zhu et al, 2006;Zhang et al, 2009] and a decrease in intracellular ATP [Chang et al, 2009;Deschepper et al, 2011].…”

“…Some authors consider short-term hypoxic exposure of MSCs to be permanently maintained under ambient O 2 (20%) as oxidative stress, which may cause functional impairment due to increased ROS production [Guzy and Schumacker, 2006;Zhang et al, 2009;Busletta et al, 2011;Peterson et al, 2011] in part triggered by a significant increase in prooxidants, such as the ROS producer NAD(P)H oxidase subunits p67phox and p47phox [Peterson et al, 2011]. A decrease in activity of the antioxidant enzyme catalase, a major metaboliser of ROS, without changes in SOD and SOD subunit levels confirmed that the metabolism of ROS was also impaired (or at least not sufficient) [Peterson et al, 2011].…”

Induction of apoptosis by casticin in cervical cancer cells: reactive oxygen species-dependent sustained activation of Jun N-terminal kinase

“…There is an integrated system of clearing ROS in the body to keep balance. Oxidation of cell membrane phospholipids, enzyme, and DNA [24][25][26][27] by high levels of ROS can alter function of signal transduction, platelet aggregation, immune control, and the regulation of cell growth, and they can also cause necrosis or apoptosis [28][29][30][31]. As the generation of ROS is the result of disordered functioning of mitochondria and metabolite augmentation, there may be ways to regulate ROS selectively in cancer cells [12,32].…”