Minocycline prevents paraquat-induced cell death through attenuating endoplasmic reticulum stress and mitochondrial dysfunction

Chuen Lin Huang, Yi Chao Lee, Ying Chen Yang, Tsun Yung Kuo, Nai Kuei Huang

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

Paraquat (PQ) was demonstrated to induce dopaminergic neuron death and is used as a Parkinson's disease (PD) mimetic; however, its mechanism remains contradictory. Alternatively, minocycline is a second-generation tetracycline and is undergoing clinical trials for treating PD with an unresolved mechanism. We thus investigated the molecular mechanism of minocycline in preventing PQ-induced cytotoxicity. In this study, minocycline was effective in preventing PQ-induced apoptotic cell death, which involves the cleavages of poly (ADP-ribose) polymerase (PARP) and caspase 3 and increased fluorescence intensity of annexin V-FITC. In addition, PQ also quickly induced alterations of unfolded protein responses (UPRs) and subsequently dysfunction of the mitochondria (such as the decrease in membrane potential and increase in membrane permeability and superoxide formation). Finally, the mechanism of minocycline in preventing PQ-induced apoptosis might be mediated by attenuating endoplasmic reticulum (ER) stress and mitochondrial dysfunction, which respectively results in caspase-12 activation and the release of H 2O 2, HtrA2/Omi, and Smac/Diablo. Thus, minocycline could possibly be used to treat other neurodegenerative disorders with similar pathologic mechanisms.

Original languageEnglish
Pages (from-to)203-210
Number of pages8
JournalToxicology Letters
Volume209
Issue number3
DOIs
Publication statusPublished - Mar 25 2012

Keywords

  • Endoplasmic reticulum stress
  • Minocycline
  • Mitochondrial dysfunction
  • Paraquat

ASJC Scopus subject areas

  • Toxicology

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