Effect of hydrogen sulphide on beta-amyloid-induced damage in PC12 cells.
1. Hydrogen sulphide (H(2)S) is a well-known cytotoxic gas. Recently, H(2)S has been shown to protect neurons against oxidative stress caused by glutamate, peroxynitrite and HOCl. Considerably lower H(2)S levels have been reported in the brain of Alzheimer's disease (AD) patients with accumulation of beta-amyloid (A beta). 2. The aim of present study was to explore the cytoprotection by H(2)S against A beta(25-35)-induced apoptosis and the molecular mechanisms underlying this effect in PC12 cells. 3. Our findings indicated that A beta(25-35) significantly reduced cell viability and induced apoptosis of PC12 cells, along with dissipation of the mitochondrial membrane potential (MMP) and overproduction of reactive oxygen species (ROS). 4. Sodium hydrosulphide (NaHS), an H(2)S donor, protected PC12 cells against A beta(25-35)-induced cytotoxicity and apoptosis not only by reducing the loss of MMP, but also by attenuating the increase in intracellular ROS. 5. The results of the present study suggest that the cytoprotection by H(2)S is related to the preservation of MMP and attenuation of A beta(25-35)-induced intracellular ROS generation. These findings could significantly advance therapeutic approaches to the neurodegenerative diseases that are associated with oxidative stress, such as AD.
Tang
Xiao-Qing
XQ
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China.
Yang
Chun-Tao
CT
Chen
Jing
J
Yin
Wei-Lan
WL
Tian
Shao-Wen
SW
Hu
Bi
B
Feng
Jian-qiang
JQ
Li
Yuan-Jian
YJ
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C439320:amyloid beta-protein (25-36); D006862:Hydrogen Sulfide