NITRIC-OXIDE PRODUCED BY ACTIVATED ASTROCYTES RAPIDLY AND REVERSIBLY INHIBITS CELLULAR RESPIRATION

被引:173
作者
BROWN, GC [1 ]
BOLANOS, JP [1 ]
HEALES, SJR [1 ]
CLARK, JB [1 ]
机构
[1] INST NEUROL,DEPT NEUROCHEM,LONDON WC1N 3BG,ENGLAND
关键词
ASTROCYTES; NITRIC OXIDE; MITOCHONDRIAL RESPIRATION; CYTOCHROME OXIDASE; ENDOTOXIN; CYTOKINES;
D O I
10.1016/0304-3940(95)11703-Y
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Cultured astrocytes, activated to express the inducible form of nitric oxide synthase, produced up to 1 mu M nitric oxide (NO) measured by a NO-selective electrode, while non-activated cells produced no detectable NO. The production of NO was associated with an inhibition of cellular respiration, measured simultaneously by an oxygen electrode. The inhibition of respiration was rapidly reversed by inhibiting the NO synthase or by binding the NO with haemoglobin. The respiratory inhibition had an NO, oxygen and substrate dependence consistent with NO-inhibition at cytochrome oxidase. This is the first demonstration that cells can reversibly inhibit mitochondrial respiration via NO production. This inhibition is large and potentially important in a range of pathophysiological conditions.
引用
收藏
页码:201 / 204
页数:4
相关论文
共 13 条
[1]   CYTOTOXICITY OF MICROGLIA [J].
BANATI, RB ;
GEHRMANN, J ;
SCHUBERT, P ;
KREUTZBERG, GW .
GLIA, 1993, 7 (01) :111-118
[2]  
BOLANOS JP, 1994, J NEUROCHEM, V63, P910
[3]   NITRIC-OXIDE - A PHYSIOLOGICAL MESSENGER MOLECULE [J].
BREDT, DS ;
SNYDER, SH .
ANNUAL REVIEW OF BIOCHEMISTRY, 1994, 63 :175-195
[4]   NANOMOLAR CONCENTRATIONS OF NITRIC-OXIDE REVERSIBLY INHIBIT SYNAPTOSOMAL RESPIRATION BY COMPETING WITH OXYGEN AT CYTOCHROME-OXIDASE [J].
BROWN, GC ;
COOPER, CE .
FEBS LETTERS, 1994, 356 (2-3) :295-298
[5]   REVERSIBLE INHIBITION OF CYTOCHROME-C-OXIDASE, THE TERMINAL ENZYME OF THE MITOCHONDRIAL RESPIRATORY-CHAIN, BY NITRIC-OXIDE - IMPLICATIONS FOR NEURODEGENERATIVE DISEASES [J].
CLEETER, MWJ ;
COOPER, JM ;
DARLEYUSMAR, VM ;
MONCADA, S ;
SCHAPIRA, AHV .
FEBS LETTERS, 1994, 345 (01) :50-54
[6]   NITRIC-OXIDE MEDIATES GLUTAMATE NEUROTOXICITY IN PRIMARY CORTICAL CULTURES [J].
DAWSON, VL ;
DAWSON, TM ;
LONDON, ED ;
BREDT, DS ;
SNYDER, SH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (14) :6368-6371
[7]   A REDOX-BASED MECHANISM FOR THE NEUROPROTECTIVE AND NEURODESTRUCTIVE EFFECTS OF NITRIC-OXIDE AND RELATED NITROSO-COMPOUNDS [J].
LIPTON, SA ;
CHOI, YB ;
PAN, ZH ;
LEI, SZZ ;
CHEN, HSV ;
SUCHER, NJ ;
LOSCALZO, J ;
SINGEL, DJ ;
STAMLER, JS .
NATURE, 1993, 364 (6438) :626-632
[8]  
MERRILL JE, 1993, J IMMUNOL, V151, P2132
[9]   MACROGLIA - NEURAL CELLS RESPONSIVE TO LYMPHOKINES AND GROWTH-FACTORS [J].
MERRILL, JE .
IMMUNOLOGY TODAY, 1987, 8 (05) :146-150
[10]   SYNTHESIS OF NITRIC-OXIDE IN CNS GLIAL-CELLS [J].
MURPHY, S ;
SIMMONS, ML ;
AGULLO, L ;
GARCIA, A ;
FEINSTEIN, DL ;
GALEA, E ;
REIS, DJ ;
MINCGOLOMB, D ;
SCHWARTZ, JP .
TRENDS IN NEUROSCIENCES, 1993, 16 (08) :323-328