Nowak G, Aleo M D, Morgan J A, Schnellmann R G
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205-7199, USA.
Am J Physiol. 1998 Mar;274(3):F509-15. doi: 10.1152/ajprenal.1998.274.3.F509.
This study investigated the recovery of renal proximal tubule cellular (RPTC) functions following oxidant-induced sublethal injury. tert-Butylhydroperoxide (TBHP) treatment resulted in 24% cell death and loss 4 h following the exposure. The remaining sublethally injured RPTC proliferated, and monolayer DNA content returned to control values on day 4 following TBHP exposure. Basal oxygen consumption (Qo2) and ATP content in sublethally injured RPTC were decreased 64 and 63%, respectively, at 4 h and returned to control values on day 6. Net lactate consumption decreased 71% at 4 h and returned to control values on day 4. In contrast, net glutamine consumption increased 2.7-fold at 4 h and returned to control values on day 6. Ouabain-sensitive Qo2, Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) activity, and Na(+)-coupled glucose transport were inhibited 77, 88, and 83%, respectively, at 4 h and recovered to control values on day 6. These data show that 1) mitochondrial function, Na(+)-K(+)-ATPase activity, active Na+ transport, and Na(+)-coupled glucose transport are decreased in sublethally injured RPTC following oxidant exposure and are repaired over time; 2) monolayer regeneration precedes the recovery of mitochondrial and transport functions, and 3) sublethal injury and subsequent regeneration are associated with alterations in metabolic substrate utilization. These results suggest that oxidant-induced sublethal injury to RPTC may contribute to renal dysfunction and that RPTC can repair and regain cellular functions following oxidant injury.
本研究调查了氧化剂诱导的亚致死性损伤后肾近端小管细胞（RPTC）功能的恢复情况。暴露后4小时，叔丁基过氧化氢（TBHP）处理导致24%的细胞死亡和丢失。其余亚致死性损伤的RPTC增殖，TBHP暴露后第4天单层DNA含量恢复至对照值。亚致死性损伤的RPTC在4小时时基础氧消耗（Qo2）和ATP含量分别下降64%和63%，并在第6天恢复至对照值。净乳酸消耗在4小时时下降71%，并在第4天恢复至对照值。相比之下，净谷氨酰胺消耗在4小时时增加2.7倍，并在第6天恢复至对照值。哇巴因敏感的Qo2、钠钾腺苷三磷酸酶（Na(+)-K(+)-ATPase）活性和钠偶联葡萄糖转运在4小时时分别被抑制77%、88%和83%，并在第6天恢复至对照值。这些数据表明：1）氧化剂暴露后亚致死性损伤的RPTC中线粒体功能、Na(+)-K(+)-ATPase活性、活性钠转运和钠偶联葡萄糖转运下降，并随时间修复；2）单层再生先于线粒体和转运功能的恢复；3）亚致死性损伤及随后的再生与代谢底物利用的改变有关。这些结果表明，氧化剂诱导的RPTC亚致死性损伤可能导致肾功能障碍，且RPTC在氧化剂损伤后可修复并恢复细胞功能。
