Minocycline up-regulates BCL-2 levels in mitochondria and attenuates male germ cell apoptosis.
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.
Castanares
Mark
M
Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, David Geffen School of Medicine at UCLA, Torrance, CA 90509, USA.
Vera
Yanira
Y
Erkkilä
Krista
K
Kyttänen
Sauli
S
Lue
Yanhe
Y
Dunkel
Leo
L
Wang
Christina
C
Swerdloff
Ronald S
RS
Hikim
Amiya P Sinha
AP
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D005854:Germ Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology; D006170:Gum Arabic / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D008297:Male; D008911:Minocycline / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D015854:Up-Regulation
D000900:Anti-Bacterial Agents; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C489013:DIABLO protein, rat; D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D006170:Gum Arabic; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D008911:Minocycline