Minocycline up-regulates BCL-2 levels in mitochondria and attenuates male germ cell apoptosis

被引:33
作者
Castanares, M
Vera, Y
Erkkilä, K
Kyttänen, S
Lue, YH
Dunkel, L
Wang, C
Swerdloff, RS
Hikim, APS [1 ]
机构
[1] Harbor UCLA Med Ctr, Dept Med, Div Endocrinol, Torrance, CA 90509 USA
[2] Univ Calif Los Angeles, Los Angeles Biomed Res Inst, David Geffen Sch Med, Torrance, CA 90509 USA
[3] Biomedicum, Program Dev & Reprod Biol, FIN-00029 Helsinki, Finland
[4] Univ Helsinki, Hosp Children & Adolescents, FIN-00029 Helsinki, Finland
[5] Kuopio Univ Hosp, Dept Pediat, FIN-70211 Kuopio, Finland
关键词
apoptosis; hormone withdrawal; minocycline; BCL-2; cytochrome c; DIABLO; germ cells; testis;
D O I
10.1016/j.bbrc.2005.09.101
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
In this study, we determined the efficacy of minocycline, a second generation tetracycline, in preventing male germ cell apoptosis after withdrawal of gonadotropins and intratesticular testosterone (T). Groups of 5 male rats received one of the following treatments daily for 5 days: (i) daily sc injection of GnRH-A (1.6 mg/kg BW), (ii) oral administration of 30% gum acacia as a vehicle control, and (iii) GnRH-A + oral administration of 50 or 100 mg/kg BW of minocycline. Minocycline at both 50 and 100 mg dose levels significantly (P < 0.05) prevented GnRH-A-induced germ cell apoptosis by 59.4% and 62.2%, respectively, and fully prevented PARP cleavage. Minocycline-mediated protection occurred at the mitochondria, involving the restoration of the BCL-2 levels and, in turn, suppression of cytochrome c and DIABLO release. Minocycline was also effective in preventing human male germ cell apoptosis induced by hormone free culture condition. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:663 / 669
页数:7
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