Caffeine activates the PI3K/Akt pathway and prevents apoptotic cell death in a Parkinson's disease model of SH-SY5Y cells.
Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Recent epidemiological studies suggest that caffeine, one of the major components of coffee, has a protective effect against developing PD. However, the detailed mechanisms of how caffeine suppresses neuronal death have not been fully elucidated. We investigated the cytoprotective mechanisms of caffeine using human dopaminergic neuroblastoma SH-SY5Y cells as a PD model. Caffeine prevented the apoptotic cell death induced by serum/retinoic acid (RA) deprivation, MPP+, rotenone, and 6-OHDA in SH-SY5Y cells in a dose dependent manner. Caffeine lowered caspase-3 activity induced by serum/RA deprivation and 6-OHDA administration, and also decreased the number of apoptotic condensed and/or fragmented nuclei. Akt was phosphorylated 60 min after caffeine administration in a dose dependent manner; PI3K inhibitors, wortmannin and LY294002 canceled this cytoprotective effect of caffeine. On the other hand, MAPKs such as Erk1/2, p38, or JNK were not activated by caffeine. These results suggest that caffeine has a cytoprotective effect due to the activation of the PI3K/Akt pathways in SH-SY5Y cells.
Nakaso
Kazuhiro
K
Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36-1 Nishicho, Yonago, 683-8504, Japan. kazuhiro@grape.med.tottori-u.ac.jp
Ito
Satoru
S
Nakashima
Kenji
K
D000978:Antiparkinson Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019610:Cytoprotection / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D010300:Parkinson Disease / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D000978:Antiparkinson Agents; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D009498:Neurotoxins; D010726:Phosphodiesterase Inhibitors; D002110:Caffeine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt