Humanin protects neurons against apoptosis induced by Abeta31-35 through suppression of intrinsic pathway.
The present study aimed to investigate the effects of humanin (HN) on primary cortical neuronal apoptosis induced by Abeta31-35, and explore the potential mechanisms. Cultured cortical neurons were pretreated with different concentrations of HN (5, 10, 20 micromol/L) for different time period (0, 8 and 16 h) respectively, and then exposed to Abeta31-35 (25 micromol/L) for additional 24 h and the neuronal apoptosis was examined by morphological analysis, flow cytometric assays and TUNEL staining. Caspase activities were measured using a spectrophotometer. Bax expression was measured by Western blot. The results were as follows. (1) Pretreatment with HN (20 micromol/L) for 16 h significantly prevented Abeta31-35-induced apoptosis in cortical neurons; (2) HN significantly decreased Abeta31-35-induced elevation of caspase-3 and -9 activities; (3) HN suppressed Abeta31-35-induced translocation of Bax from the cytosol to mitochondria, but had no effect on overall Bax expression. In conclusions, HN attenuated Abeta31-35-induced cortical neuronal apoptosis by blocking intrinsic caspase-dependent apoptotic pathways.
Li
Ling-Min
LM
Department of Pathology, Shanxi Medical University, Taiyuan 030001, China.
Zhang
Yu
Y
Qiao
Jian-Tian
JT
Zhang
Ce
C
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D047908:Intracellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C113042:amyloid beta-protein (31-35); C427211:humanin; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9