Melatonin attenuates amyloid beta25-35-induced apoptosis in mouse microglial BV2 cells.
Melatonin has been reported to possess strong antioxidant actions, and is able to directly scavenge a variety of reactive oxygen species (ROS). The present study investigated whether melatonin possesses protective effects against Abeta-induced cytotoxicity in microglial cells. Cells treated with Abeta exhibited several characteristic features of apoptosis, while cells pre-treated with melatonin prior to exposure to Abeta showed a decrease in the occurrence of such apoptotic features. Several previous studies have demonstrated the involvement of ROS in Abeta-induced neurotoxicity, and ROS generated by Abeta have been reported to lead to the activation of nuclear factor-kappa B (NF-kappaB), a transcription factor; pre-treatment with melatonin in the present study reduced the level of Abeta-induced intracellular ROS generation, inhibited NF-kappaB activation, and suppressed the Abeta-induced increase in caspase-3 enzyme activity. In addition, it was found that pre-treatment with melatonin inhibits Abeta-induced increase in the levels of bax mRNA and that it enhances the level of bcl-2 expression. Based on these findings, the authors speculate that melatonin may provide an effective means of treatment for Alzheimer's disease through attenuation of Abeta-induced apoptosis.
Jang
Mi-Hyeon
MH
Department of Physiology, College of Medicine, Kyung Hee University, Seoul, South Korea.
Jung
Sae-Bin
SB
Lee
Myoung-Hwa
MH
Kim
Chang-Ju
CJ
Oh
Young-Taek
YT
Kang
Insug
I
Kim
Jeongseon
J
Kim
Ee-Hwa
EH
D000111:Acetylcysteine / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D051028:bcl-2-Associated X Protein
D016229:Amyloid beta-Peptides; D000975:Antioxidants; C494827:Bax protein, mouse; D016328:NF-kappa B; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); D051028:bcl-2-Associated X Protein; D004247:DNA; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D008550:Melatonin; D000111:Acetylcysteine