ABSTRACT
We reviewed again the significance of the stable gastric pentadecapeptide BPC 157 as a likely mediator of Robert's stomach cytoprotection/adaptive cytoprotection and organoprotection and as novel mediator of Selye's stress coping response to reestablish homeostasis. Specific points of BPC 157 therapy and the original concept of Robert's cytoprotection/adaptive cytoprotection/organoprotection are discussed, including the beneficial effects of BPC 157. First, BPC 157 protects stomach cells and maintains gastric integrity against various noxious agents (Robert's killing cell by contact) and is continuously present in the gastric mucosa and gastric juice. Additionally, BPC 157 protects against the adverse effects of alcohol and nonsteroidal anti-inflammatory drugs on the gastric epithelium and other epithelia, that is, skin, liver, pancreas, heart (organoprotection), and brain, thereby suggesting its use in wound healing. Additionally, BPC 157 counteracts gastric endothelial injury that precedes and induces damage to the gastric epithelium and generalizes "gastric endothelial protection" to protection of the endothelium of other vessels (thrombosis, prolonged bleeding, and thrombocytopenia). BPC 157 also has an effect on blood vessels, resulting in vessel recruitment that circumvents vessel occlusion and the development of additional shunting and rapid bypass loops to rapidly reestablish the integrity of blood flow (ischemic/reperfusion colitis, duodenal lesions, cecal perforation, and inferior vena caval occlusion). Lastly, BPC 157 counteracts tumor cachexia, muscle wasting, and increases in pro-inflammatory/procachectic cytokines, such as interleukin-6 and tumor necrosis factor-α, and significantly corrects deranged muscle proliferation and myogenesis through changes in the expression of FoxO3a, p-AKT, p-mTOR, and p-GSK-3ß (mitigating cancer cachexia).
Subject(s)
Adaptation, Physiological/drug effects , Cytoprotection/drug effects , Gastric Mucosa/drug effects , Peptide Fragments/pharmacology , Protective Agents/pharmacology , Proteins/pharmacology , Gastrointestinal Tract/drug effects , HumansABSTRACT
AIM To study the adaptive cytoprotection of H 2O 2 preconditioning against oxidative stress damage in PC12 cell and the relationships between brain derived neurotrophic factor (BDNF) and the adaptive cytoprotection of H 2O 2 preconditioning. METHODS The viability of PC12 cells was evaluated by MTT assay. Apoptosis was detected by PI stain flow cytometer. Expression of BDNF was analyzed by immuo flow cytometer. RESULTS After H 2O 2 preconditioning, the survival of PC12 cells exposure to H 2O 2 (20～60 ?mol?L -1 ) was increased and the apoptosis of PC12 cells induced by H 2O 2 (20 or 30 ?mol?L -1 ) was inhibited and the expression of BDNF in PC12 cells was enhanced. CONCLUSION H 2O 2 preconditioning is protective against the damage of PC12 cells induced by H 2O 2 and its mechanisms may involve up modulation of the expression of BDNF.
ABSTRACT
AIM: To explore the role of extracellular signal-regulated kinases ERK1/2-STAT3 pathway in adaptive cytoprotection induced by H2O2 preconditioning in PC12 cells.METHODS: In PC12 cells,the experimental model of cytoprotection by H2O2 preconditioning against oxidative stress-induced injury was set up.The morphological changes in the apoptotic cells were observed by using of chromatin dye Hoechst 33258.The percent of apoptotic cells was determined by flow cytometry(FCM) with propidium iodide staining.The levels of p-ERK1/2 and p-STAT3 expression were detected by Western blotting assay.RESULTS: Preconditioning with H2O2 at concentration of 100 ?mol/L for 90 min obviously inhibited apoptosis induced by 300 ?mol/L H2O2,and both ERK1/2 and STAT3 were activated.UO126(10 ?mol/L,an inhibitor of ERK1/2) or AG-490(10?mol/L,an inhibitor of JAK2) significantly blocked the cytoprotection effect of H2O2 preconditioning.Moreover,UO126(10 ?mol/L) also markedly inhibited the up-regulation of p-STAT3 expression by H2O2 preconditioning.CONCLUSION: H2O2 preconditioning activates ERK1/2-STAT3 signal pathway,which may be one of the mechanisms underlying H2O2 preconditioning-induced cytoprotection.
