Intracellular acidosis protects cultured hepatocytes from the toxic consequences of a loss of mitochondrial energization.
Intracellular acidosis protects cultured hepatocytes from the toxic consequences of a loss of mitochondrial energization.
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细胞内酸中毒可以保护培养的肝细胞免受线粒体能量丧失的毒性后果。
DOI：
10.1016/0003-9861(89)90206-3
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发表时间：
1989
影响因子：
3.9
通讯作者：
Farber,JL
中科院分区：
文献类型：
--
作者：
Masaki,N;Thomas,AP;Hoek,JB;Farber,JL
培养的大鼠肝细胞分别用细胞色素氧化酶抑制剂氰化钾、钾离子载体呋喃霉素、原载体间氯苯肼(CCCP)和三磷酸腺苷合成酶抑制剂寡霉素处理。这些药物对细胞活力的影响与ATP含量的变化和线粒体的失能有关。三种抑制剂均可使细胞内ATP含量降低90%以上。除寡霉素外，其余药剂均在4h内杀死细胞，用~(3 H)三苯甲基膦分布测定线粒体膜电位后，线粒体膜电位随各药剂浓度的升高而降低。H+Na+离子载体莫能菌素能增强氰化物和CCCP的毒性，而降低呋喃霉素的毒性。用荧光探针2‘，7’-双羧乙基-5，6-羧基荧光素测定氰化物和莫能菌素对培养肝细胞胞浆pH的影响。氰化物迅速酸化胞质，10μm莫能菌素的加入使胞质迅速碱化。将培养液的pH值从7.4降至6.6和6.0可防止氰化物和氰化物在莫能菌素存在下对细胞的杀灭。然而，莫能菌素和胞外酸化对氰化物存在下线粒体的能量丧失没有任何影响。结论是，ATP本身的耗竭不足以解释氰化物、CCCP和呋喃霉素对细胞的杀伤作用。相反，细胞死亡与线粒体能量丧失有更好的相关性。氰化物引起的细胞内酸中毒干扰了线粒体膜电位崩溃致死细胞损伤的机制。
Cultured rat hepatocytes were treated with potassium cyanide, an inhibitor of cytochrome oxidase; valinomycin, a K+ ionophore; carbonyl cyanide m-chlorophenylhydrazone (CCCP), a protonophore; and the ATP synthetase inhibitor oligomycin. The effect of these agents on the viability of the cells was related to changes in ATP content and the deenergization of the mitochondria. The ATP content was reduced by over 90% by each inhibitor. All of the agents except oligomycin killed the cells within 4 h. With the exception of oligomycin, the mitochondrial membrane potential as measured by the distribution of [3 H] triphenylmethylphosphonium collapsed with each of the agents. Monensin, a H+ Na+ ionophore, potentiated the toxicity of cyanide and CCCP, whereas the toxicity of valinomycin was reduced. The effect of cyanide and monensin on the cytoplasmic pH of cultured hepatocytes was measured with the fluorescent probe, 2′, 7′-biscarboxyethyl-5, 6-carboxyfluorescein. Cyanide promptly acidified the cytosol, and the addition of 10 μ m monensin caused a rapid alkalinization of the cytosol. A reduction of pH of the culture medium from 7.4 to 6.6 and 6.0 prevented the cell killing both by cyanide alone and by cyanide in the presence of monensin. However, neither monensin nor extra-cellular acidosis had any effect on the loss of mitochondrial energization in the presence of cyanide. It is concluded that ATP depletion per se is insufficient to explain the cell killing with cyanide, CCCP, and valinomycin. Rather, cell killing is better correlated with a loss of mitochondrial energization. With cyanide an intracellular acidosis interferes with the mechanism that couples collapse of the mitochondrial membrane potential to lethal cell injury.
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莫能菌素对培养的大鼠卵巢颗粒细胞中蛋白多糖的合成、运输和细胞内降解的影响。
DOI：
10.1016/s0021-9258(18)89043-3
发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
M. Yanagishita;V. Hascall
通讯作者：
V. Hascall
培养肝细胞中不可逆细胞损伤的钙依赖性和钙非依赖性机制。
DOI：
--
发表时间：
1986
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Starke,PE;Hoek,JB;Farber,JL
通讯作者：
Farber,JL
DOI：
10.1016/s0021-9258(19)77928-9
发表时间：
1988-02
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
P. Hyslop;Daniel;Hinshawz;Wayne A. Halsey;Ingrid;Schraufstatter;Richard D. Sauerhebery;Roger G. Spraggj;Janis H. Jackson;C G Cochrane
通讯作者：
P. Hyslop;Daniel;Hinshawz;Wayne A. Halsey;Ingrid;Schraufstatter;Richard D. Sauerhebery;Roger G. Spraggj;Janis H. Jackson;C G Cochrane
钠质子交换的激活是人血小板中 Ca2+ 动员的先决条件
影响因子：
64.8
作者：
W. Siffert;J. Akkerman
通讯作者：
J. Akkerman
缺氧大鼠肝细胞中磷脂降解加速。
影响因子：
3.9
作者：
J. Farber;Ellora E. Young
通讯作者：
Ellora E. Young