摘要
目的 探讨三氧化二砷 (As2 O3)治疗白血病时的心脏不良反应机制。方法 Fluo 3/AM荧光探针标记豚鼠心室肌细胞 ,激光共聚焦显微镜实时测定不同浓度As2 O3干预后的心室肌胞浆 [Ca2 +]i,磷基转移法测定心室肌胞膜和胞浆内蛋白激酶C(PKC)的活性。结果 0 .5 μmol·L- 1As2 O3对台氏液中豚鼠心室肌细胞 [Ca2 +]i 无明显影响。 2 μmol·L- 1As2 O3持续作用 6min时 ,细胞 [Ca2 +]i 开始升高 ,持续约 9min后恢复到给药前水平。 10 μmol·L- 1As2 O3作用不到 3min时 ,心室肌细胞 [Ca2 +]i 持续升高至扫描结束共 2 7min ,一直没有恢复。As2 O3引起的 [Ca2 +]i 升高可被钙通道阻滞剂维拉帕米和硝苯地平不完全阻断。 2～ 10 μmol·L- 1AS2 O3作用3h可使细胞膜及胞浆相的PKC活性升高 ,10 μmol·L- 1组 ,细胞膜相的PKC升高更明显。结论 一定浓度的As2 O3可使心肌细胞内游离钙升高、PKC活化 ,细胞膜可能是As2 O3最初作用靶点。
AIM To clarify the mechanisms of the cardiac s ide effects of arsenic trioxide (As 2O 3) in leukemia treatment. METHODS Fluo-3/AM fluorescent probe tagged [Ca 2+] i of guinea pig′s ventriclar myocardium, detected the [Ca 2+] i by laser confocal microsc ope before and after exposed to As 2O 3. Phosphorus radioisotope assay was use d to detect the activity of protein kinase C(PKC) on cell membrane or in cytopla sm. RESULTS The cytosolic [Ca 2+] i did not change when gui nea pig′s ventricular myocardium was incubated in Tyrode′s solution with 0.5 μmol·L -1 As 2O 3. However, after incubated in 2 μmol·L -1 As 2O 3 for 6 min, [Ca 2+] i began to increase and was continuously i ncreasing for about 9 min. After exposed to 10 μmol·L -1 As 2O 3 for le ss than 3 min,the [Ca 2+] i kept on increasing till the end (about 27 min) of the examination and could not recover. The increasing of [Ca 2+] i could be partly blocked by calcium channel blocking agents verapamil and nif edipine. The activities of PKC of cells membrane and cytoplasm were activated b y AS 2O 3 2-10 μmol·L -1 after 3 h incubation. For 10 μmol·L -1 AS 2O 3, the PKC activity of cell membrane was increased more than that of cy toplasm′s. CONCLUSION As 2O 3 can activate the activity of PKC , increase the concentration of cytosolic [Ca 2+] i. The initial actio n target of As 2O 3 may be cell membrane.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2004年第6期449-452,共4页
Chinese Journal of Pharmacology and Toxicology
基金
国家自然科学基金资助项目 (30 370 5 0 7)
黑龙江省留学归国基金资助项目 (LC0 2C14 )~~
关键词
三氧化二砷
心肌
细胞膜
蛋白激酶类
钙
细胞内
arsenic trioxide
myocardium
cell membrane
protein kinases
calcium, cytosolic
