ent-Steroids: Novel tools for studies of signaling pathways

被引:57
作者
Covey, Douglas F. [1 ]
机构
[1] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA
关键词
ent-Steroid; Enantioselectivity; Enantiomer; Diastereomer; Lipid perturbation; ACID(A) RECEPTOR MODULATION; PREGNENOLONE SULFATE; ENANTIOMERIC CHOLESTEROL; GABA(A) RECEPTORS; DEHYDROEPIANDROSTERONE-SULFATE; NEUROSTEROID ANALOGS; NEUROACTIVE STEROIDS; HIPPOCAMPAL-NEURONS; CA2+ CURRENT; IN-VITRO;
D O I
10.1016/j.steroids.2008.11.019
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
Membrane receptors are often modulated by steroids and it is necessary to distinguish the effects of steroids at these receptors from effects occurring at nuclear receptors. Additionally, it may also be mechanistically important to distinguish between direct effects caused by binding of steroids to membrane receptors and indirect effects on membrane receptor function caused by steroid perturbation of the membrane containing the receptor. In this regard, ent-steroids, the mirror images of naturally occurring steroids, are novel tools for distinguishing between these various actions of steroids. The review provides a background for understanding the different actions that can be expected of steroids and ent-steroids in biological systems, references for the preparation of ent-steroids, a short discussion about relevant forms of stereoisomerism and the requirements that need to be fulfilled for the interaction between two molecules to be enantioselective. The review then summarizes results of biophysical, biochemical and pharmacological studies published since 1992 in which ent-steroids have been used to investigate the actions of steroids in membranes and/or receptor-mediated signaling pathways. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:577 / 585
页数:9
相关论文
共 89 条
[21]   Enantiospecificity of cholesterol function in vivo [J].
Crowder, CM ;
Westover, EJ ;
Kumar, AS ;
Ostlund, RE ;
Covey, DF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (48) :44369-44372
[22]   Allopregnanolone and progesterone decrease cell death and cognitive deficits after a contusion of the rat pre-frontal cortex [J].
Djebaili, M ;
Hoffman, SW ;
Steins, DG .
NEUROSCIENCE, 2004, 123 (02) :349-359
[23]   Requirement of sterols in the life cycle of the nematode Caenorhabditis elegans [J].
Entchev, EV ;
Kurzchalia, TV .
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2005, 16 (02) :175-182
[24]   Role of chirality in peptide-induced formation of cholesterol-rich domains [J].
Epand, RM ;
Rychnovsky, SD ;
Belani, JD ;
Epand, RF .
BIOCHEMICAL JOURNAL, 2005, 390 :541-548
[25]   Mannheim classification of nongenomically initiated (rapid) steroid action(s) [J].
Falkenstein, E ;
Norman, AW ;
Wehling, M .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2000, 85 (05) :2072-2075
[26]  
GALE SE, J BIOL CHEM IN PRESS
[27]  
Geva M, 2001, CHEMBIOCHEM, V2, P265, DOI 10.1002/1439-7633(20010401)2:4<265::AID-CBIC265>3.0.CO
[28]  
2-V
[29]   The nonfeminizing enantiomer of 17β-estradiol exerts protective effects in neuronal cultures and a rat model of cerebral ischemia [J].
Green, PS ;
Yang, SH ;
Nilsson, KR ;
Kumar, AS ;
Covey, DF ;
Simpkins, JW .
ENDOCRINOLOGY, 2001, 142 (01) :400-406
[30]   Niemann-Pick type C disease involves disrupted neurosteroidogenesis and responds to allopregnanolone [J].
Griffin, LD ;
Gong, WH ;
Verot, L ;
Mellon, SH .
NATURE MEDICINE, 2004, 10 (07) :704-711