MITOCHONDRIAL CALCIUM HANDLING AND OXIDATIVE STRESS
MITOCHONDRIAL CALCIUM HANDLING AND OXIDATIVE STRESS
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DOI：
10.1042/bst0210353
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发表时间：
1993-05-01
影响因子：
3.9
通讯作者：
CONNERN, CP
中科院分区：
文献类型：
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作者：
HALESTRAP, AP;GRIFFITHS, EJ;CONNERN, CP
化学中毒或缺血后再灌注的组织经历氧化应激，这是氧自由基增加和还原型谷胱甘肽减少的结果。这可能伴随着细胞质[Ca 2 +]的同时增加，这会导致能量代谢和[Ca 2 +]稳态的破坏[1-41。对这些组织的电子显微镜检查显示，它们的线粒体变得肿胀，外观上更加弥散[1，3，41]，而质子动力的平行测量显示，在相同条件下，线粒体的肿胀和扩散会减少[3-61]。随后分离的线粒体已证实，它们的功能受损。特别地，它们耗尽腺嘌呤核苷酸，并表现出不同程度的呼吸链抑制，特别是复合物I、寡霉素敏感性ATP酶和腺嘌呤核苷酸转位酶[4，7-91，在缺血/再灌注心脏中，这些作用与线粒体Ca 2+含量的增加有关，并且如果在灌注介质中存在钌红，则这些作用显著降低[7，81.多年来，人们一直认为，[7，81]。多年来，人们已经知道氧化应激和线粒体Ca 2+含量增加的组合会损害分离的线粒体[1，2，10，111]，体内观察到的影响似乎反映了相同的现象。
Tissues subjected to chemical poisoning or ischaemia followed by reperfusion experience oxidative stress as a result of both an increase in oxygen free radical species and a decrease in reduced glutathione. This may be accompanied by a simultaneous increase in cytosolic [Ca2+] which follows a disruption of energy metabolism and [Ca2+] homeostasis [1-41. Electron microscopic examination of such tissues shows that their mitochondra become swollen and more diffuse in appearance [1, 3, 41, and parallel measurements of proton motive force show this to be decreased under the same conditions [3-61. Subsequent isolation of the mitochondria has confirmed that they are functionally impaired. In particular, they are depleted of adenine nucleotides and exhibit inhibition, to varying degrees, of the respiratory chain, especially complex I, the oligomycin-sensitive ATPase and the adenine nucleotide translocase [4, 7-91, In the ischaemic/reperfused heart these effects are associated with an increase in mitochondrial Ca2+ content and are substantially reduced if ruthenium red is present in the perfusion medium [7, 81. It has been known for many years that a [7, 81. It has been known for many years that a combination of oxidative stress and increased mitochondrial Ca2+ content is damaging to isolated mitochondria [1, 2, 10, 111 and it would seem likely that the effects seen in vivo reflect the same phenomenon.