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Protective effect of histamine H2 receptor antagonist ranitidine against rotenone-induced apoptosis

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Abstract

Histamine H2 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 H2 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 NH2-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.

Original languageEnglish
Pages (from-to)1114-1119
Number of pages6
JournalNeuroToxicology
Volume30
Issue number6
DOIs
Publication statusPublished - Nov 2009

Bibliographical note

Funding Information:
This research was supported by the Kyung Hee University Post-Doctoral Research Fund in 2008 ( KHU-20080525 ).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • Apoptosis
  • Parkinson's disease
  • Ranitidine
  • Rotenone
  • SH-SY5Y cells

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