[Effects of humanin on elevation of intracellular calcium concentration induced by beta-amyloid peptide(31-35) in cultured cortical neurons.].
The disruption of the intracellular Ca(2+) homeostasis has been reported to be one of the mechanisms of beta-amyloid (Abeta) neurotoxicity in Alzheimeros disease (AD). Abeta(31-35), a small active fragment of Abeta, is believed to possess the similar biological activities of full-length Abeta molecule. Humanin (HN) is a recently identified peptide that suppresses neuronal death initiated by AD-related insults. The present study was to investigate the effects of HN on Abeta(31-35)-induced elevation of [Ca(2+)](i) in cultured cortical neurons by real-time fluorescence imaging technique using the Ca(2+)-sensitive dye, Fura-2/AM. The elevation of [Ca(2+)](i) was observed in cultured neurons exposed to Abeta(31-35) (25 mumol/L) (F340/F380: 1 042.56+/- 83.54, compared with control group: 804.73+/- 48.230, P<0.05, n=10). Pretreatment of HN (10 mumol/L) for 10 min significantly decreased the elevation of [Ca(2+)](i) induced by Abeta(31-35) (25 mumol/L) (F340/F380: 918.788+/- 50.73, compared with Abeta(31-35) group, P<0.05, n=10). When neurons were treated with HN and Abeta(31-35) simultaneously, HN (10 mumol/L) could not change the elevation of [Ca(2+)](i) induced by Abeta(31-35) (F340/F380: 1 036.68+/- 88.96, compared with Abeta(31-35) group, P>0.05, n=10), while HN (20 mumol/L) diminished the elevation of [Ca(2+)](i) induced by Abeta(31-35) (25 mumol/L) significantly (F340/F380: 898.56+/- 76.46, compared with Abeta(31-35) group, P<0.05, n=10). The findings imply that: (1) the disruption of the calcium homeostasis induced by Abeta(31-35) is possibly the basis of the neurotoxicity of Abeta(31-35) in cultured cortical neurons; (2) HN suppresses the elevation of [Ca(2+)](i) induced by Abeta(31-35) in a dose- and time-dependent manner.
Department of Pathology, Shanxi Medical University, Taiyuan, China.
Ling-Min
LM
Li
Jian-Tian
JT
Qiao
Ce
C
Zhang
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death; D002478:Cells, Cultured; D006706:Homeostasis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D047908:Intracellular Signaling Peptides and Proteins; D010446:Peptide Fragments; C113042:amyloid beta-protein (31-35); C427211:humanin; D002118:Calcium