title: Differential modulation of apoptotic gene expression by N-acetyl-L-cysteine in Leydig cells stimulated persistently with hCG in vivo.
abstract: The present study was designed to investigate the molecular mechanisms of NAC (150 mg/kg bw twice/week) action in vivo under repeated hCG (100 IU/rat/day) stimulation to adult rats. Leydig cell refractoriness led to a significant decline in serum testosterone and intracellular cAMP by day 30 of chronic hCG intervention which improved significantly following NAC co-administration. It inhibited the rise in lipid peroxidation, improved the activity of antioxidant enzymes along with intracellular glutathione and total antioxidant capacity in the target cells. Leydig cell apoptosis declined significantly (P<0.001) with down-regulation of upstream, Fas, FasL, caspase-8, Bax and caspase-9, JNK/pJNK and downstream caspase-3 and PARP. On the other hand, anti-apoptotic Bcl2, NF-kβ, and Akt were up-regulated. Taken together, the above findings indicate that the specificity of NAC action was not restricted to regulating marker proteins in the extrinsic and JNK pathways as seen in vitro but extended to include intrinsic pathway of metazoan apoptosis as well.
authors.affiliation: Department of Reproductive Biomedicine, National Institute of Health and Family Welfare, Baba Gang Nath Marg, Munirka, New Delhi 110067, India.
authors.forename: Archana
authors.initials: A
authors.lastname: Aggarwal
authors.forename: M M
authors.initials: MM
authors.lastname: Misro
authors.forename: Ankur
authors.initials: A
authors.lastname: Maheshwari
authors.forename: Neeta
authors.initials: N
authors.lastname: Sehgal
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009929:Organ Size; D018384:Oxidative Stress; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012102:Reproductive Control Agents / Q000494:pharmacology*; D013091:Spermatogenesis / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013739:Testosterone / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D016166:Free Radical Scavengers; D047908:Intracellular Signaling Peptides and Proteins; D012102:Reproductive Control Agents; D017392:Thiobarbituric Acid Reactive Substances; D016159:Tumor Suppressor Protein p53; D013739:Testosterone; D000242:Cyclic AMP; D002374:Catalase; D013482:Superoxide Dismutase; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D005982:Glutathione Transferase; C505410:Casp3 protein, rat; D053148:Caspase 3; D005978:Glutathione; D000111:Acetylcysteine