Radix Salviae miltiorrhiza (RSM, 'Dansham' in Korea, 'Danshen' in Chinese), the root of Salviae miltiorrhiza Bunge (Labiate) has been used as Chinese fork medicine for the treatment of cardiovascular diseases such as angina pectoris, coronary heart disease, myocardial infarction, and hypertension. In the present study, we evaluated the inhibitory effects of 15,16-Dihydrotanshinone I, one of the major ingredients of Salvia miltiorrhiza Bunge, on platelet aggregation, with elucidation of its mechanisms of action. 15,16-Dihydrotanshinone I concentration-dependently inhibited collagen-induced aggregation of rabbit washed platelets with IC50 of 8.7+/-5.6 microM, the potency being about seven-fold greater than EGCG, an active Green tea catechin component (IC50: 56.6+/-48.7 microM). 15,16-Dihydrotanshinone I significantly inhibited the intracellular calcium ([Ca2+]i) mobilization in a concentration-dependent manner. 15,16-dihdydrotanshinone I also significantly suppressed collagen (50 microg/mL)-induced liberation of [3H]Arachidonic acid from [3H]Arachidonic acid-incorporated rabbit platelet. In addition, 15,16-Dihydrotanshinone I at 50 microM slightly but significantly inhibited collagen-induced production of thromboxane B2. These results indicate that 15,16-Dihydrotanshinone I exert potent anti-platelet activity via suppression of [Ca2+]i mobilization and arachidonic acid liberation.
In this study, we have compared the skeletal muscle proteome at various stages of porcine postnatal development.Korean native pigs were divided into five postnatal stages of 30, 70, 130, 170 and 300 d and their loin muscles were analyzed for muscle proteome by using two-dimensional electrophoresis and mass spectrometry. We found 5 proteins showing a consistent pattern during skeletal muscle growth. Four proteins were identified as myosin light chain 1 slow-twitch (MLC1sa) isoform, troponin T, triosephosphate isomerase (TIP) and DJ-1 protein. The remaining protein was not identified. Two muscle fiber proteins of MLC1sa isoform and troponin T showed a high expression level at an early postnatal stage and then their levels were decreased markedly during growth stages. On the other hand, the expression of TIP and DJ-1 protein, which are well known as catalysis enzyme and antioxidantrelated protein, respectively, were linearly increased during growth stages. Thus, the stage-related muscle proteins may be useful as parameters for understanding the developmental characteristics of biochemical and physiological properties in Korean native pig skeletal muscle.
To investigate the involvement of reperfusion-induced salvage kinases (RISK) as possible signaling molecules for the cardioprotective effects of BMS-180448, a prototype mitochondrial ATP-sensitive K+ (mitoK(ATP)) channel opener, we measured its cardioprotective effects in a rat model of ischemia/reperfusion (I/R) heart injury, together with western blotting analysis of five different signaling proteins. In isolated rat hearts subjected to 30-min global ischemia followed by 30-min reperfusion, BMS-180448 (1, 3 and 10 microM) significantly increased reperfusion left ventricular developed pressure (LVDP) and 30-min reperfusion double product (heart rate x LVDP) in a concentration-dependent manner, while decreasing left ventricular end-diastolic pressure (LVEDP) throughout reperfusion period in a concentration-dependent manner. SDS-PAGE/western blotting analysis of left ventricle reperfused for 30 min revealed that BMS-180448 significantly decreased phospho-GSK3beta at high concentration, whereas it tended to increase slightly phospho-eNOS and phospho-p70S6K with concentration. However, BMS-180448 had no effect on phospho-Akt and phospho-Bad. These results suggest that the cardioprotective effects of BMS-180448 against I/R heart injury may result from direct activation of mitoK(ATP) channel in cardiomyocytes, with the minimal role of RISK pathway in the activation of this channel and the cardioprotective effects of BMS-180448.
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