Multiple functions of type 10 17β-hydroxysteroid dehydrogenase

被引:106
作者
Yang, SY
He, XY
Schulz, H
机构
[1] New York State Inst Basic Res Dev Disabil, Dept Pharmacol, Staten Isl, NY 10314 USA
[2] CUNY City Coll, Dept Chem & Biochem, New York, NY 10031 USA
关键词
D O I
10.1016/j.tem.2005.03.006
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Human 17 beta-hydroxysteroid dehydrogenase type 10 (17 beta-HSD10) is a mitochondrial enzyme encoded by the SCHAD gene, which escapes chromosome X inactivation. 17 beta-HSD10/SCHAD mutations cause a spectrum of clinical conditions, from mild mental retardation to progressive infantile neurodegeneration. 17 beta-HSD10/SCHAD is essential for the metabolism of isoleucine and branched-chain fatty acids. It can inactivate 17 beta-estradiol and steroid modulators of GABA(A) receptors, and convert 5 alpha-androstanediol into 5 alpha-dihydrotestosterone (DHT). Certain malignant prostatic epithelial cells contain high levels of 17 beta-HSD10, generating 5 alpha-DHT in the absence of testosterone. 17 beta-HSD10 has an affinity for amyloid-beta peptide, and might be linked to the mitochondrial dysfunction seen in Alzheimer's disease. This versatile enzyme might provide a new drug target for neuronal excitability control and for intervention in Alzheimer's disease and certain cancers.
引用
收藏
页码:167 / 175
页数:9
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共 62 条
[1]   N-methyl-D-aspartate receptor mRNA levels change during reproductive senescence in the hippocampus of female rats [J].
Adams, MM ;
Morrison, JH ;
Gore, AC .
EXPERIMENTAL NEUROLOGY, 2001, 170 (01) :171-179
[2]   A juvenile hector's beaked whale, Mesoplodon hectori (Gray 1871), without functional throat grooves, plus notes on endoparasites (Cetacea: Ziphiidae) [J].
Baker, AN ;
Duignan, PJ ;
Norman, RJD ;
Van Helden, AL .
MARINE MAMMAL SCIENCE, 2001, 17 (01) :171-175
[3]   Expression cloning and characterization of oxidative 17 beta- and 3 alpha-hydroxysteroid dehydrogenases from rat and human prostate [J].
Biswas, MG ;
Russell, DW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (25) :15959-15966
[4]   Evolution of 17β-HSD type 4, a multifunctional protein of β-oxidation [J].
Breitling, R ;
Marijanovic, Z ;
Perovic, D ;
Adamski, J .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2001, 171 (1-2) :205-210
[5]   Structure-based phylogenetic analysis of short-chain alcohol dehydrogenases and reclassification of the 17beta-hydroxysteroid dehydrogenase family [J].
Breitling, R ;
Laubner, D ;
Adamski, J .
MOLECULAR BIOLOGY AND EVOLUTION, 2001, 18 (12) :2154-2161
[6]   Phosphatidylcholine activation of human heart (R)-3-Hydroxybutyrate dehydrogenase mutants lacking active center sulfhydryls:: Site-directed mutagenesis of a new recombinant fusion protein [J].
Chelius, D ;
Loeb-Hennard, C ;
Fleischer, S ;
McIntyre, JO ;
Marks, AR ;
De, SM ;
Hahn, S ;
Jehl, MM ;
Moeller, J ;
Philipp, R ;
Wise, JG ;
Trommer, WE .
BIOCHEMISTRY, 2000, 39 (32) :9687-9697
[7]   Characterization of a novel type of human microsomal 3α-hydroxysteroid dehydrogenase -: Unique tissue distribution and catalytic properties [J].
Chetyrkin, SV ;
Belyaeva, OV ;
Gough, MH ;
Kedishvili, NY .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (25) :22278-22286
[8]   Brain 5α-dihydroprogesterone and allopregnanolone synthesis in a mouse model of protracted social isolation [J].
Dong, E ;
Matsumoto, K ;
Uzunova, V ;
Sugaya, I ;
Takahata, H ;
Nomura, H ;
Watanabe, H ;
Costa, E ;
Guidotti, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (05) :2849-2854
[9]   Role of ERAB/L-3-hydroxyacyl-coenzyme A dehydrogenase type II activity in Aβ-induced cytotoxicity [J].
Du Yan, S ;
Shi, YG ;
Zhu, AP ;
Fa, J ;
Zhu, HJ ;
Zhu, YC ;
Gibson, L ;
Stern, E ;
Collison, K ;
Al-Mohanna, F ;
Ogawa, S ;
Roher, A ;
Clarke, SG ;
Stern, DM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (04) :2145-2156
[10]   Human types 1 and 3 3α-hydroxysteroid dehydrogenases:: Differential lability and tissue distribution [J].
Dufort, I ;
Labrie, F ;
Luu-The, V .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (02) :841-846