Role of mitochondrial-derived oxidants in renal tubular cell cold-storage injury.
Role of mitochondrial-derived oxidants in renal tubular cell cold-storage injury.
复制标题
DOI：
10.1016/j.freeradbiomed.2010.07.012
复制
发表时间：
2010-11-01
影响因子：
7.4
通讯作者：
MacMillan-Crow, Lee Ann
中科院分区：
文献类型：
--
作者：
Mitchell, Tanecia;Saba, Hamida;Laakman, Joe;Parajuli, Nirmala;MacMillan-Crow, Lee Ann
关键词：
冷冻保存（CS）被认为是捐献已故供者肾脏的必要程序，有助于优化器官活力。在CS和再灌注（或再温/CS）过程中，氧化剂生成增加。RW期被认为是肾损伤的主要因素；虽然来源和/或与氧化剂生产有关的生化途径尚不清楚。本研究的目的是确定肾小管线粒体超氧化物是否能够在CS反应中诱导氧化剂产生和线粒体损伤。RW侮辱。检测线粒体超氧化物在CS中的作用。RW损伤时，我们使用过表达锰超氧化物歧化酶（MnSOD）的大鼠肾近端小管（NRK）细胞，锰超氧化物歧化酶是线粒体主要抗氧化剂。NRK细胞暴露于CS.RW后，氧化剂产生、线粒体膜电位、呼吸复合体功能和细胞死亡均发生改变。MnSOD过表达或抑制一氧化氮合酶（NOS）对氧化剂生成、呼吸复合体失活和细胞死亡具有重要的保护作用。这些发现暗示线粒体超氧化物、一氧化氮及其反应产物过氧亚硝酸盐是参与CS的关键信号分子。RW损伤的肾小管细胞，并提示治疗性抑制这些途径可能保护供体肾脏。
Cold storage (CS) is regarded as a necessary procedure during donation of a deceased donor kidney that helps to optimize organ viability. Increased oxidant generation during both CS as well as during the reperfusion (or rewarming/CS.RW) phase have been suggested to be a major contributor to renal injury; although the source and/or biochemical pathways involved with oxidant production remain unclear. The purpose of this study was to determine if renal tubular mitochondrial superoxide is capable of inducing oxidant production and mitochondrial damage in response to a CS.RW insult. To test the role of mitochondrial superoxide in CS.RW injury, we used rat renal proximal tubular (NRK) cells overexpressing manganese superoxide dismutase (MnSOD), the major mitochondrial antioxidant. Oxidant production, mitochondrial membrane potential, respiratory complex function, and cell death were all altered following exposure of NRK cells to CS.RW. MnSOD overexpression or inhibition of nitric oxide synthase (NOS) provided significant protection against oxidant generation, respiratory complex inactivation, and cell death. These findings implicate mitochondrial superoxide, nitric oxide, and their reaction product, peroxynitrite, as key signaling molecules involved in CS.RW injury of renal tubular cells, and suggest that therapeutic inhibition of these pathways may protect the donor kidney.
登录
查看更多内容
影响因子：
4.1
作者：
Han, D;Williams, E;Cadenas, E
通讯作者：
Cadenas, E
影响因子：
20.1
作者：
GRIENDLING, KK;MINIERI, CA;ALEXANDER, RW
通讯作者：
ALEXANDER, RW
影响因子：
7.4
作者：
Davis, Christiana W.;Hawkins, Brian J.;Ramasamy, Subbiah;Irrinki, Krishna M.;Cameron, Bruce A.;Islam, Khalid;Daswani, Varsha P.;Doonan, Patrick J.;Manevich, Yefim;Madesh, Muniswamy
通讯作者：
Madesh, Muniswamy
影响因子：
4.8
作者：
Murray, J;Taylor, SW;Capaldi, RA
通讯作者：
Capaldi, RA
DOI：
10.1196/annals.1341.022
发表时间：
2005-01-01
期刊：
COMMUNICATIVE CARDIAC CELL
影响因子：
--
作者：
Honda, HM;Korge, P;Weiss, JN
通讯作者：
Weiss, JN