Journal of Molecular Neuroscience

, Volume 50, Issue 1, pp 70–77

Role of Paraoxonase-1 in the Protection of Hydrogen Sulfide-Donating Sildenafil (ACS6) Against Homocysteine-Induced Neurotoxicity

Authors

    • Institute of Cognition and Nervous System Diseases, Medical CollegeUniversity of South China
    • Department of Physiology, Medical CollegeUniversity of South China
  • Rong-Qian Chen
    • Institute of Cognition and Nervous System Diseases, Medical CollegeUniversity of South China
    • Department of PhysiologyChuzhou City Vocation College
  • Ling Dong
    • Department of Pathology, Medical CollegeUniversity of South China
  • Yan-Kai Ren
    • Institute of Cognition and Nervous System Diseases, Medical CollegeUniversity of South China
    • Department of Physiology, Medical CollegeUniversity of South China
  • Piero Del Soldato
    • CTG Pharma
  • Anna Sparatore
    • Department of Pharmaceutical Sciences “Pietro Pratesi”Università degli Studi di Milano
    • Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (incubation)Hunan University of Chinese Medicine
Article

DOI: 10.1007/s12031-012-9862-x

Cite this article as:
Tang, X., Chen, R., Dong, L. et al. J Mol Neurosci (2013) 50: 70. doi:10.1007/s12031-012-9862-x

Abstract

ACS6, a novel hydrogen sulfide (H2S)-releasing sildenafil, has been demonstrated to inhibit superoxide formation through donating H2S. We have previously found that ACS6 antagonizes homocysteine-induced apoptosis and cytotoxicity. The aim of the present study is to explore the molecular mechanisms underlying ACS6-exerted protective action against the neurotoxicity of homocysteine. In the present work, we used PC12 cells to explore whether paraoxonase-1 (PON-1) is implicated in ACS6-induced neuroprotection against homocysteine neurotoxicity. We show that ACS6 treatment results in prevention of homocysteine-caused neurotoxicity and overproduction of reactive oxygen species (ROS). Homocysteine downregulates the expression and activity of PON-1; however, this effect is significantly blocked by co-treatment with ACS6. The specific inhibitor of PON-1 2-hydroxyquinoline reverses the inhibitory effect of ACS6 on homocysteine-induced neurotoxicity and intracellular ROS accumulation. These results indicate that ACS6 protects PC12 cells against homocysteine-induced neurotoxicity by upregulating PON-1 and suggest a promising role of PON-1 as a novel therapeutic strategy for homocysteine-induced toxicity.

Keywords

H2S-releasing sildenafilHomocysteineNeurotoxicityParaoxonase-1Reactive oxygen species

Copyright information

© Springer Science+Business Media, LLC 2012