The Regulation Of PD On The Activities Of PKC In VSMC And Cardiomyocytes Under The Stimulation Of Hypoxia,burn Serum And LPS

The regulation of PD on the activities of PKC in VSMC and Cardiomyocytes under the stimulation of hypoxia~ burn serum and LPS Abstract Polydatin(PD) is a small molecule substance purified from Chinese traditional herb Polygonum cuspidatum, which was found to have a good effects in the treatment against hemorrhagic shock, burn shock and septic shock in animals and patients. The previous works have demonstrated that PD in vivo can dilate blood vessles, increase pulse pressure, enhance the contractile force of cardiac muscle. These suggested that the effects of PD are related to the contractibility of vascular smooth muscle cells(VSMC) and myocardiocytes, but the molecular and cellular mechanisms is not clear. It is well known that protein kinase C (PKC) is an important second messenger in cells, it can regulate the contractibility of VSMC and myocardiocyte. It is likely that PD regulate the function of VSMC and myocardiocyte through PKC signal pathway. In order to investigate the mechanism of PD. we observed PKC activities in cultured VSMC and myocardiocytes of rats which are stimulated by ischemic hypoxia, burn serum and LPS to mimic the conditions of hemorrhagic shock, burn shock and septic shock. In the experiment, the PKC were purified by DE-52 cellulose chromatography, and measured by y-32P-ATP scintillation counting. When cultured VSMCs are treated with lOOng/ml of LPS, or placed in ischemic hypoxia circumstance for 4 hours, the PKC activity decreased in cytoplasm, and increased with burn serum stimulation. But the activity of PKC in membrane of VSMC -5- were different from that in cytoplasm, the activity of PKC in ischemic hypoxia treatment was decreased, but increased in LPS and burn serum treatment.. In myocardial cells experiment, we found that all of stimulating factors reduced the activity of PKC in cytoplasm. The activity of membrane PKC enhanced in LPS and burn serum treated group, and reduced in ischemic hypoxia group. From the above results, we conclude that PKC activities may changed during the pathological stimulation of LPS, ischemic hypoxia, and burn serum; the effects of PD may be mediated by PKC signal transduction pathway so as ~o regulate the contractibility of VSMC and myocardiocytes. PD can antagonize the damage effects by reversing the PKC activities. When the injurious stimulation enhance the activity of PKC, PD can abate it; when injurious stimulation abate the activity of PKC, PD can enhance it. The detail mechanisms of PD regulating the PKC activity need further investigation.