Protective effect of histamine H2 receptor antagonist ranitidine against rotenone-induced apoptosis.
Histamine H(2) receptor antagonists have been reported to improve the motor symptoms of Parkinson's disease (PD) patients and to exert neuroprotective effects. In this study, we investigated the protective effects of the H(2) receptor antagonist ranitidine on rotenone-induced apoptosis in human dopaminergic SH-SY5Y cells, focusing on mitogen-activated protein kinases (MAPKs) and caspases (CASPs)-mediated apoptotic events. Ranitidine blocked the rotenone-induced phosphorylation of c-Jun NH(2)-terminal protein kinase (JNK) and P38 MAPK (P38), and promoted the phosphorylation of extracellular signal-regulated protein kinase (ERK). Ranitidine also prevented the down-regulation of B-cell CLL/lymphoma 2 (BCL2) and the up-regulation of BCL2-associated X protein (BAX) by rotenone. Furthermore, ranitidine not only attenuated rotenone-induced cleavages of CASP9, poly(ADP-ribose) polymerase-1 (PARP) and CASP3, but also suppressed CASP3 enzyme activity. These results indicate that ranitidine protects against rotenone-induced apoptosis, inhibiting phosphorylation of JNK and P38, and activation of CASPs in human dopaminergic SH-SY5Y cells.
Park
Hae Jeong
HJ
Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Kim
Hak Jae
HJ
Park
Hyun-Kyung
HK
Chung
Joo-Ho
JH
D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007211:Indoles; D007306:Insecticides / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011899:Ranitidine / Q000494:pharmacology*; D012402:Rotenone / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D006635:Histamine H2 Antagonists; D007211:Indoles; D007306:Insecticides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D012402:Rotenone; C007293:DAPI; D011899:Ranitidine; D011065:Poly(ADP-ribose) Polymerases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9