Paper Information

Title: 

CELL-TYPE SPECIFIC MODULATION OF PROTEINASE-ACTIVATED RECEPTOR-2 EXPRESSION BY CROCIN, IMPLICATIONS TO NEURODEGENERATIVE DISORDERS

Type: POSTER
Author(s): AFKHAMI AMIR*,SHAFIEI SH.
 
 *DEPARTMENT OF PHARMACOLOGY, SCOOL OF VETERINARY MEDICINE, FERDOWSI UNIVERSITY OF MASHHAD, MASHHAD, 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: 

Crocin, an active constituent of saffron (Crocus sativus L.) has widely been known for its antioxidant properties, which nominate this herbal compound to be having theraputic value in the neurodegenerative disroders. Alzheimer’s disease (AD) is a neurodegenerative disorder defined by misfolded protein accumulation and free radicals generation with concurrent neuroinflammation and neuronal death. The proteinase-activated receptors (PARs) are a novel family of G proteincoupled receptors, which mediate both neuroprotective and neuropathogenic effects, although their effects in neurodegenerative diseases remain uncertain. We have previously reported that PAR2 can exert protective properties in neurons, but its activation in glia is pathogenic with secretion of neurotoxic factors and suppression of astrocytic anti-inflammatory mechanisms contributing to amyloidbeta 1-42 aminoacids (Aβ1-42) -mediated neurodegeneration, probably through altering the NF-κB activity. In another study of these series we have also reported that crocin is capable of protecting neurons against Aβ1-42 -induced oxidative injury in vitro. This effect was also confirmed by in vivo experiments indicating that crocin can decrease the Aβ1-42 -induced lipid peroxidation and increase the total thiol and antioxidant power of the brain. To glean insight into the potential mechanism of this protection, fetal neurons, astrocytes and microglia were isolated from 17-day old rat fetuses, cultured and treated with different increasing concentrations of crocin (1, 5, 10, 20, 50, 100 and 200 μM). The results disclosed that crocin was capable of upregulating the expression of proteinase-activated receptor-2 (PAR2) in neurons, while the microglial and astrocytic PAR2 expression was downregulated by crocin in a concentration-dependent manner (P<0.05). This unique cell-type specific effect was shown at both protein and mRNA levels, using Intracellular Western Assay (LiCOR) and real-time RT-PCR, respectively. These findings divulge a new pattern of protection in which crocin can specifically change the expression of PAR2 in different cell types of the nervous system.

 
Keyword(s): CROCIN, AD, PAR-2, NEURON, ASTROCYTE, MICROGLIA
 
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