Free radicals mediate actions of oxyhemoglobin on cerebrovascular smooth muscle cells.
Free radicals mediate actions of oxyhemoglobin on cerebrovascular smooth muscle cells.
复制标题
自由基介导氧合血红蛋白对脑血管平滑肌细胞的作用。
DOI：
10.1161/01.res.68.2.416
复制
发表时间：
1991
影响因子：
20.1
通讯作者：
Weir,B
中科院分区：
文献类型：
--
作者：
Steele,JA;Stockbridge,N;Maljkovic,G;Weir,B
采用酶解分离法从大鼠基底动脉中分离单个平滑肌细胞。使用膜片电极电压钳技术评估细胞的膜特性，并使用双醋酸荧光素摄取来监测细胞活力。细胞暴露于氧合血红蛋白（5微米）导致1)收缩，2)膜泡的出现，3)向外钾电流增加，4)膜电阻降低，5)细胞死亡。相比之下，氧合血红蛋白对培养的小鼠神经母细胞瘤细胞没有影响。高铁血红蛋白（100微米）对平滑肌细胞无影响。过氧化氢酶（300单位/ml）或二甲基亚砜（0.5%）可防止氧合血红蛋白的影响；超氧化物歧化酶（100-1,000单位/ml）仅提供部分保护。将细胞暴露于黄嘌呤（1mm）加黄嘌呤氧化酶（10单位/升）或过氧化氢（500微米）产生的超氧阴离子中，会增加向外钾电流，但不影响膜电阻。金属离子和过氧化氢产生羟基自由基，产生与氧合血红蛋白相同的效果，即钾电流增加，随后膜阻力降低和细胞死亡。综上所述，氧合血红蛋白对血管平滑肌细胞的作用似乎是通过产生自由基，主要是羟基自由基。
Single smooth muscle cells were isolated from the basilar artery of the rat by enzymatic dispersion. The membrane properties of the cells were assessed using the patch-electrode voltage-clamp technique, and cell viability was monitored using fluorescein diacetate uptake. Exposure of the cells to oxyhemoglobin (5 microM) resulted in 1) contraction, 2) the appearance of membrane blebs, 3) an increase in the outward potassium currents, 4) a decrease in the membrane resistance, and 5) cell death. In contrast, no effect of oxyhemoglobin on cultured murine neuroblastoma cells was observed. Methemoglobin (100 microM) had no effects on the smooth muscle cells. Catalase (300 units/ml) or dimethyl sulfoxide (0.5%) protected against the effects of oxyhemoglobin; superoxide dismutase (100-1,000 units/ml) provided only partial protection. Exposure of the cells to superoxide anions generated by xanthine (1 mM) plus xanthine oxidase (10 units/l) or to hydrogen peroxide (500 microM) caused an increase in the outward potassium currents without affecting membrane resistance. Generation of hydroxyl radicals by metal ions plus hydrogen peroxide caused the same effects as oxyhemoglobin, that is, an increase in the potassium currents, followed by a decrease in the membrane resistance and cell death. In conclusion, it appears that oxyhemoglobin exerts its effects on vascular smooth muscle cells by the generation of free radicals, chiefly hydroxyl radicals.