Involvement of nitric oxide-mediated intrinsic pathway signaling in age-related increase in germ cell apoptosis in male Brown-Norway rats.
We examined, using young and old Brown-Norway rats, the involvement of the nitric oxide (NO)-mediated intrinsic pathway signaling in age-related activation of male germ-cell apoptosis. Increased apoptosis of germ cells was readily observed in the normal-looking testes of old rats. Testicular NO synthase (NOS) activity, assessed by measuring the synthesis of (3)H-L-citrulline from (3)H-L-arginine, and cytokine-inducible NO synthase (iNOS) levels, assessed by western blot assay, were increased significantly by 90% and 70%, respectively, in the old rats compared to that of young animals. Immunohistochemical analysis of age-related changes in the expression of iNOS in testes confirmed our findings based on western blot assay. Increased NO and germ-cell apoptosis during aging is further associated with cytosolic translocation of mitochondrial cytochrome c and poly (ADP) ribose polymerase (PARP) cleavage, thus, suggesting the involvement of NO-mediated intrinsic pathway signaling in age-related increase in germ-cell apoptosis in male Brown-Norway rats.
Division of Endocrinology, Box 446, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90509, USA. hikim@gcrc.rei.edu
Amiya P Sinha
AP
Hikim
Yanira
Y
Vera
Dolores
D
Vernet
Mark
M
Castanares
Maruja
M
Diaz-Romero
Monica
M
Ferrini
Ronald S
RS
Swerdloff
Nestor F
NF
Gonzalez-Cadavid
Christina
C
Wang
D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D005854:Germ Cells / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D011914:Rats, Inbred BN; D015398:Signal Transduction / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000201:enzymology
D009419:Nerve Tissue Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat