ABSTRACT
BACKGROUND@#Resveratrol has been shown to inhibit platelet aggregation. However, the mechanism for this action of resveratrol remains to be clarified. The purpose of this study was to elucidate the Ca@*METHODS@#Ca@*RESULTS@#Thapsigargin-induced Ca@*CONCLUSIONS@#The results suggest that resveratrol inhibits thrombin-induced platelet aggregation through decreasing Ca
Subject(s)
Humans , Antioxidants/administration & dosage , Calcium/physiology , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/pharmacology , Resveratrol/pharmacology , Signal Transduction/drug effectsABSTRACT
Radiation therapy for variety of human solid tumors utilizes mechanism of cell death after DNA damage caused by radiation. In response to DNA damage, cytochrome c was released from mitochondria by activation of pro-apoptotic Bcl-2 family proteins, and then elicits massive Ca2+ release from the ER that lead to cell death. It was also suggested that irradiation may cause the deregulation of Ca2+ homeostasis and trigger programmed cell death and regulate death specific enzymes. Thus, in this study, we investigated how cellular Ca2+ metabolism in RKO cells, in comparison to radiation-resistant A549 cells, was altered by gamma (gamma)-irradiation. In irradiated RKO cells, Ca2+ influx via activation of NCX reverse mode was enhanced and a decline of [Ca2+]i via forward mode was accelerated. The amount of Ca2+ released from the ER in RKO cells by the activation of IP3 receptor was also enhanced by irradiation. An increase in [Ca2+]i via SOCI was enhanced in irradiated RKO cells, while that in A549 cells was depressed. These results suggest that gamma-irradiation elicits enhancement of cellular Ca2+ metabolism in radiation-sensitive RKO cells yielding programmed cell death.
Subject(s)
Humans , Calcium , Cell Death , Colorectal Neoplasms , Cytochromes c , DNA Damage , Homeostasis , Inositol 1,4,5-Trisphosphate Receptors , Metabolism , MitochondriaABSTRACT
AIM To study the characteristics of Ca 2+ channel mediated store operated Ca 2+ influx on rat vascular smooth muscle. METHOD Fura 2 fluorescence technique was used to investigate the [Ca 2+ ] i change. RESULTS ① S nitrosocaptopril (CapNO,20～120 ?mol?L -1 ) produced a concentration dependent inhibitory effect on cyclopiazonic acid(CPA) induced [Ca 2+ ] i change. The maximal inhibitory effect(37%?17%) of CapNO was reached at a concentration of 80 ?mol?L -1 . The same concentration of Captopril had no effects. ② Inhibition rate of 80 ?mol?L -1 CapNO (The concentration of maximal effect, CME) on CPA induced [Ca 2+ ] i change was 30%?10%, subsequent addition of 1 ?mol?L -1 Nif (CME)did not further produced the decrease effect (54%?18%). subsequent addition of 20 ?mol?L -1 SK&F96365 (CME) further produced the decrease effect. The inhibitory effects of 20 ?mol?L -1 SK&F96365 were significantly different in the cases of CapNO and Nif pretreatment(24%?10%) and non treatment (54%?11%). ③ The inhibitory effects of 2 ?mol?L -1 tyrphostinAG490(AG490,CME) were significantly different in the cases of CapNO (CME) pretreatment (24%?9%)and non treatment (42%?10%). 80 ?mol?L -1 CapNO effect on CPA induced [Ca 2+ ] i changes in AG490 pretreatment condition(18%?7%) was different from that in non treatment case(37%?10%). CONCLUSION S nitrosocaptopril obviously inhibits the opening of SOCC and VDCC, which mediates store operated Ca 2+ influx. The inhibitory effects of CapNO is associated with both sensitive to and non sensitive to tyrosine kinase (Janus2).