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 journalArticle

28 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

Fingerprint

Minocycline
Paraquat
Endoplasmic Reticulum Stress
Cell death
Cell Death
Parkinson Disease
Caspase 12
Membranes
Unfolded Protein Response
Mitochondria
Poly(ADP-ribose) Polymerases
Fluorescein-5-isothiocyanate
Annexin A5
Dopaminergic Neurons
Cytotoxicity
Tetracycline
Superoxides
Caspase 3
Neurodegenerative Diseases
Membrane Potentials

Keywords

  • Endoplasmic reticulum stress
  • Minocycline
  • Mitochondrial dysfunction
  • Paraquat

ASJC Scopus subject areas

  • Toxicology

Cite this

Minocycline prevents paraquat-induced cell death through attenuating endoplasmic reticulum stress and mitochondrial dysfunction. / Huang, Chuen Lin; Lee, Yi Chao; Yang, Ying Chen; Kuo, Tsun Yung; Huang, Nai Kuei.

In: Toxicology Letters, Vol. 209, No. 3, 25.03.2012, p. 203-210.

Research output: Contribution to journalArticle

Huang, Chuen Lin ; Lee, Yi Chao ; Yang, Ying Chen ; Kuo, Tsun Yung ; Huang, Nai Kuei. / Minocycline prevents paraquat-induced cell death through attenuating endoplasmic reticulum stress and mitochondrial dysfunction. In: Toxicology Letters. 2012 ; Vol. 209, No. 3. pp. 203-210.
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