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Paper Information

Title: 

A SALEN-MANGANESE CATALYTIC FREE RADICAL SCAVENGER (EUK134) INHIBITS HYDROGEN PEROXIDE INDUCED NEURONAL APOPTOSIS IN SK-N-MC CELLS

Type: POSTER
Author(s): MOHAMMADI MOHSEN*,YAZDANPARAST RAZIEH
 
 *INSTITUTE OF BIOCHEMISTRY AND BIOPHYSICS, TEHRAN UNIVERSITY, TEHRAN, IRAN
 
Name of Seminar: IRANIAN CONGRESS OF PHYSIOLOGY AND PHARMACOLOGY
Type of Seminar:  CONGRESS
Sponsor:  PHYSIOLOGY AND PHARMACOLOGY SOCIETY, MASHHAD UNIVERSITY OF MEDICAL SCIENCE
Date:  2009Volume 19
 
 
Abstract: 

Alzheimer’s disease (AD) is a common, devastating neurodegenerative disease characterized by progressive memory loss and dementia. Presence of extracellular senile plaques and intraneuronal neurofibrillary tangles are the pathological hallmarks of AD. One of the underlying mechanisms of AD appears to be accumulation of b-amyloid peptide (Ab) and its deposition in plaques. Generation of reactive oxygen species (ROS) and oxidative stress is proposed as the main mechanism of Ab neurotoxicity and one of the hallmarks of AD. However, how oxidative stress induces neuronal apoptosis is not well understood. To address this question, human neuroblastoma cell line (SK-N-MC) was exposed to hydrogen peroxide (H2O2), a major oxidant generated when oxidative stress occurs. We observed that H2O2 induced generation of reactive oxygen species (ROS), leading to apoptosis of the cells. In addition, H2O2 activated the mitogen-activated protein kinases (MAPK) including extracellular signal-regulated kinase 1/2 (ERK1/2), c- Jun N-terminal kinase (JNK) and p38. We also found that H2O2 induces lipid peroxidation, caspase 3 activation, over expression of Bax and p53 and down regulation of Bcl2. Inhibition of ERK1/2, JNK or p38 with kinase inhibitors prevented H2O2-induced apoptosis. In other hand, pretreatment with a salenmanganese complex (EUK134) scavenged H2O2-induced ROS, blocking activation of MAPKs and cell death. In addition, EUK134 decreased expression of proapoptotic gene p53 and Bax and enhanced expression of anti-apoptotic Bcl-2 gene. The results suggest that H2O2 induces the activation of ERK1/2, JNK and p38 pathways thereby resulting in neuronal apoptosis. Our findings suggest that inhibitors of MAPKs (JNK, ERK1/2 and p38) or antioxidants may have potentials to prevent and treat oxidative stress-induced neurodegenerative diseases such as AD.

 
Keyword(s): ALZHEIMER’S DISEASE, APOPTOSIS, EUK134, MAPK, P53
 
 
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