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

  • Xiao-Qing Tang
  • Rong-Qian Chen
  • Ling Dong
  • Yan-Kai Ren
  • Piero Del Soldato
  • Anna Sparatore
  • Duan-Fang Liao


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.


H2S-releasing sildenafil Homocysteine Neurotoxicity Paraoxonase-1 Reactive oxygen species 


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Xiao-Qing Tang
    • 1
    • 2
  • Rong-Qian Chen
    • 1
    • 6
  • Ling Dong
    • 7
  • Yan-Kai Ren
    • 1
    • 2
  • Piero Del Soldato
    • 4
  • Anna Sparatore
    • 5
  • Duan-Fang Liao
    • 3
  1. 1.Institute of Cognition and Nervous System Diseases, Medical CollegeUniversity of South ChinaHengyangPeople’s Republic of China
  2. 2.Department of Physiology, Medical CollegeUniversity of South ChinaHengyangPeople’s Republic of China
  3. 3.Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (incubation)Hunan University of Chinese MedicineChangshaPeople’s Republic of China
  4. 4.CTG PharmaMilanItaly
  5. 5.Department of Pharmaceutical Sciences “Pietro Pratesi”Università degli Studi di MilanoMilanItaly
  6. 6.Department of PhysiologyChuzhou City Vocation CollegeChuzhouPeople’s Republic of China
  7. 7.Department of Pathology, Medical CollegeUniversity of South ChinaHengyangPeople’s Republic of China

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