Biochemical dysfunction in heart mitochondria exposed to ischaemia and reperfusion

被引:189
作者
Solaini, G [1 ]
Harris, DA [1 ]
机构
[1] Scuola Super Sant Anna, Classe Accadem Sci Sperimentali, I-56127 Pisa, Italy
关键词
F1F0-ATPase; ischaemia; mitochondria; reactive oxygen species (ROS); reperfusion;
D O I
10.1042/BJ20042006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Heart tissue is remarkably sensitive to oxygen deprivation. Although heart cells, like those of most tissues, rapidly adapt to anoxic conditions, relatively short periods of ischaemia and subsequent reperfusion lead to extensive tissue death during cardiac infarction. Heart tissue is not readily regenerated, and permanent heart damage is the result. Although mitochondria maintain normal heart function by providing virtually all of the heart's ATP, they are also implicated in the development of ischaemic damage. While mitochondria do provide some mechanisms that protect against ischaemic damage (such as an endogenous inhibitor of the F1F0-ATPase and antioxidant enzymes), they also possess a range of elements that exacerbate it, including ROS (reactive oxygen species) generators, the mitochondrial permeability transition pore, and their ability to release apoptotic factors. This review considers the process of ischaemic damage from a mitochondrial viewpoint. It considers ischaemic changes in the inner membrane complexes I-V, and how this might affect formation of ROS and high-energy phosphate production/ degradation. We discuss the contribution of various mitochondrial cation channels to ionic imbalances which seem to be a major cause of reperfusion injury. The different roles of the H+, Ca2+ and the various K+ channel transporters are considered, particularly the K-ATP(+) (ATP-dependent K+) channels. A possible role for the mitochondrial permeability transition pore in ischaemic damage is assessed. Finally, we summarize the metabolic and pharmacological interventions that have been used to alleviate the effects of ischaemic injury, highlighting the value of these or related interventions in possible therapeutics.
引用
收藏
页码:377 / 394
页数:18
相关论文
共 263 条
[81]   Reduction of ischemia and reperfusion-induced myocardial damage by cytochrome P450 inhibitors [J].
Granville, DJ ;
Tashakkor, B ;
Takeuchi, C ;
Gustafsson, AB ;
Huang, CQ ;
Sayen, MR ;
Wentworth, P ;
Yeager, M ;
Gottlieb, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (05) :1321-1326
[82]   The IF1 inhibitor protein of the mitochondrial F1F0-ATPase [J].
Green, DW ;
Grover, GJ .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 2000, 1458 (2-3) :343-355
[83]   Preconditioning in rat hearts is independent of mitochondrial F1F0 ATPase inhibition [J].
Green, DW ;
Murray, HN ;
Sleph, PG ;
Wang, FL ;
Baird, AJ ;
Rogers, WL ;
Grover, GJ .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1998, 274 (01) :H90-H97
[84]   MITOCHONDRIAL NONSPECIFIC PORES REMAIN CLOSED DURING CARDIAC ISCHEMIA, BUT OPEN UPON REPERFUSION [J].
GRIFFITHS, EJ ;
HALESTRAP, AP .
BIOCHEMICAL JOURNAL, 1995, 307 :93-98
[85]   RUTHENIUM RED IMPROVES POSTISCHEMIC CONTRACTILE FUNCTION IN ISOLATED RAT HEARTS [J].
GROVER, GJ ;
DZWONCZYK, S ;
SLEPH, PG .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1990, 16 (05) :783-789
[86]   Pivotal role of superoxides generated in the mitochondrial respiratory chain in peroxynitrite-dependent activation of phospholipase A2 [J].
Guidarelli, A ;
Cantoni, O .
BIOCHEMICAL JOURNAL, 2002, 366 :307-314
[87]   Apoptosis repressor with caspase recruitment domain protects against cell death by interfering with Bax activation [J].
Gustafsson, ÅB ;
Tsai, JG ;
Logue, SE ;
Crow, MT ;
Gottlieb, RA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (20) :21233-21238
[88]   Effectiveness of ischemic preconditioning on long-term myocardial preservation [J].
Hachida, M ;
Lu, H ;
Ohkado, A ;
Hoshi, H ;
Gu, H ;
Nakanishi, T ;
Koyanagi, H .
TRANSPLANTATION, 1998, 65 (08) :1021-1024
[89]   Elucidating the molecular mechanism of the permeability transition pore and its role in reperfusion injury of the heart [J].
Halestrap, AP ;
Kerr, PM ;
Javadov, S ;
Woodfield, KY .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 1998, 1366 (1-2) :79-94
[90]  
HALLIWELL B, 1989, BIOL MED