ALTERATION OF THE ADRENAL ANTIOXIDANT DEFENSE SYSTEM DURING AGING IN RATS

被引:88
作者
AZHAR, S [1 ]
CAO, LC [1 ]
REAVEN, E [1 ]
机构
[1] STANFORD UNIV, SCH MED, DEPT MED, PALO ALTO, CA 94304 USA
关键词
LIPID PEROXIDATION; LIPID HYDROPEROXIDES; ANTIOXIDANT ENZYMES; NONENZYMATIC ANTIOXIDANTS; STEROIDOGENESIS;
D O I
10.1172/JCI118177
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The goal of this study was to determine to what extent aging affects the antioxidant defense system of the rat adrenal and to evaluate the impact of any change in this system on the recognized age-related decline in steroidogenic capacity of adrenocortical cells. The studies were conducted on young (2-5 mo) and aging (12-27 mo) Sprague-Dawley rats and involved procedures measuring steroidogenesis; oxidative damage to tissue; non enzymatic antioxidants such as vitamin C, E, and glutathione; and tissue antioxidant enzyme (Nln and CuZn superoxide dismutases, catalase, and glutathione peroxidase) activity and expression (mRNA, protein mass, and location). Some measurements were made also on rats maintained on vitamin E-deficient diets. The data show that adrenals from young animals are especially well protected against oxidative events; i.e., these adrenals show the least endogenous lipid peroxidation and the highest level of resistance to prooxidant-induced damage (of various tissues measured) and show exceedingly high levels of tissue antioxidants. Aging, on the other hand, results in oxidative changes in adrenal tissue that are generally linked in time to a reduction in efficiency of the normally protective antioxidant defense system and to the decline in corticosterone production. We speculate that these events are causally related, i.e., that the age-related reduction in oxidative mechanisms in adrenal tissues leads to oxidative damage of membrane or cytosolic factors important to cholesterol transport, and, as a consequence of this damage, cholesterol cannot reach appropriate mitochondrial cholesterol side chain cleavage sites, and corticosterone production fails.
引用
收藏
页码:1414 / 1424
页数:11
相关论文
共 65 条
[41]  
Omaye ST., 1979, METHODS ENZYMOL, V62, P1, DOI [DOI 10.1016/0076-6879(79)62181-X, 10.1016/0076-6879(79)62181-X]
[42]  
PACIFICI RE, 1991, GERONTOLOGY, V37, P166
[43]   EFFECTS OF AGING ON CHOLESTEROL CONTENT AND CHOLESTEROL-METABOLIZING ENZYMES IN THE RAT ADRENAL-GLAND [J].
POPPLEWELL, PY ;
AZHAR, S .
ENDOCRINOLOGY, 1987, 121 (01) :64-73
[44]   THE INFLUENCE OF AGE ON STEROIDOGENIC ENZYME-ACTIVITIES OF THE RAT ADRENAL-GLAND - ENHANCED EXPRESSION OF CHOLESTEROL SIDE-CHAIN CLEAVAGE ACTIVITY [J].
POPPLEWELL, PY ;
BUTTE, J ;
AZHAR, S .
ENDOCRINOLOGY, 1987, 120 (06) :2521-2528
[45]   DIFFERENTIAL-EFFECTS OF AGING ON ADRENOCORTICOTROPIN RECEPTORS, ADENOSINE 3'5'-MONOPHOSPHATE RESPONSE, AND CORTICOSTERONE SECRETION IN ADRENOCORTICAL-CELLS FROM SPRAGUE-DAWLEY RATS [J].
POPPLEWELL, PY ;
TSUBOKAWA, M ;
RAMACHANDRAN, J ;
AZHAR, S .
ENDOCRINOLOGY, 1986, 119 (05) :2206-2213
[46]  
PYLES LA, 1993, P SOC EXP BIOL MED, V202, P407
[47]   EFFECT OF AGE ON CHOLESTEROL UPTAKE AND UTILIZATION BY RAT ADRENALS .2. LIPOPROTEINS FROM YOUNG AND OLD RATS [J].
REAVEN, E ;
CAO, LC ;
AZHAR, S .
MECHANISMS OF AGEING AND DEVELOPMENT, 1994, 77 (01) :27-41
[48]   ENHANCED EXPRESSION OF GRANULOSA-CELL LOW-DENSITY-LIPOPROTEIN RECEPTOR ACTIVITY IN RESPONSE TO IN-VITRO CULTURE CONDITIONS [J].
REAVEN, E ;
TSAI, L ;
SPICHER, M ;
SHILO, L ;
PHILIP, M ;
COOPER, AD ;
AZHAR, S .
JOURNAL OF CELLULAR PHYSIOLOGY, 1994, 161 (03) :449-462
[49]   THE EFFECTS OF AGING ON THE MORPHOLOGY AND FUNCTION OF THE ZONAE-FASCICULATA AND ZONAE-RETICULARIS OF THE RAT ADRENAL-CORTEX [J].
REBUFFAT, P ;
BELLONI, AS ;
ROCCO, S ;
ANDREIS, PG ;
NERI, G ;
MALENDOWICZ, LK ;
GOTTARDO, G ;
MAZZOCCHI, G ;
NUSSDORFER, GG .
CELL AND TISSUE RESEARCH, 1992, 270 (02) :265-272
[50]   EXPRESSION OF GLUTATHIONE PEROXIDASE-I GENE IN SELENIUM-DEFICIENT RATS [J].
REDDY, AP ;
HSU, BL ;
REDDY, PS ;
LI, NQ ;
THYAGARAJU, K ;
REDDY, CC ;
TAM, MF ;
TU, CPD .
NUCLEIC ACIDS RESEARCH, 1988, 16 (12) :5557-5568