Prior heat stress enhances survival of renal epithelial cells after ATP depletion.
Prior heat stress enhances survival of renal epithelial cells after ATP depletion.
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先前的热应激可增强 ATP 耗尽后肾上皮细胞的存活率。
DOI：
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发表时间：
1996
影响因子：
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通讯作者：
S. Borkan
中科院分区：
文献类型：
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作者：
Y. Wang;S. Borkan
热应激蛋白（HSP-72）是一种可诱导的细胞保护蛋白。虽然短暂的肾缺血在体内诱导HSP-72，这是不知道是否事先热应激保护肾上皮细胞从ATP耗竭介导的损伤。为了评估这一假设，将负鼠肾（OK）细胞在不存在培养基葡萄糖的情况下暴露于氰化钠和2-脱氧-D-葡萄糖，这一策略在10分钟内将细胞ATP含量降低至对照值的< 10%，并降低细胞存活率。ATP耗尽2小时后一天，先前暴露于热应激的OK细胞（诱导HSP-72的积累）显示出显著的存活改善，（总DNA增加> 4倍），与仅经历ATP耗竭的细胞相比，较少的活体染料摄取和较少的乳酸脱氢酶（LDH）释放（分别占总LDH的23.0 +/-1.6%和34.1 +/- 1.2%）。放线菌酮完全阻止了热应激后的克隆形成，并与HSP-72的稳态含量呈正相关。在ATP耗竭后的恢复期，细胞ATP含量、线粒体ATP最大产生速率和总LDH活性均显著高于HSP-72丰富的细胞。虽然与热应激相关的保护作用可能是多因素的，但保存的细胞代谢和较高的ATP含量可以增强ATP耗竭后的细胞修复过程。
The 72-kDa heat stress protein (HSP-72) is an inducible cytoprotectant protein. Although transient renal ischemia in vivo induces HSP-72, it is not known whether prior heat stress protects renal epithelial cells from injury mediated by ATP depletion. To evaluate this hypothesis, opossum kidney (OK) cells were exposed to sodium cyanide and 2-deoxy-D-glucose in the absence of medium glucose, a maneuver that reduced cell ATP content to < 10% of the control value within 10 min and decreased cell survival. One day after 2 h of ATP depletion, OK cells previously exposed to heat stress (to induce accumulation of HSP-72) exhibited marked improvement in survival (a > 4-fold increase in total DNA), less uptake of vital dye, and less release of lactate dehydrogenase (LDH) than cells subjected to ATP depletion alone (23.0 +/- 1.6 vs. 34.1 +/- 1.2% of total LDH, respectively). Enhanced clonogenicity post-heat stress was completely prevented by cycloheximide and positively correlated with the steady-state content of HSP-72. In the recovery period after ATP depletion, cell ATP content, maximum mitochondrial ATP production rate, and total LDH activity were all significantly higher in cells with abundant HSP-72. Although the protective effects associated with heat stress are likely to be multifactoral, preserved cell metabolism and higher ATP content could enhance cellular repair processes after ATP depletion.