The neuroprotective efficacy of alpha-crystallin against acute inflammation in mice.
Acute inflammation activates macrophages or monocytes and subsequently releases several inflammatory cytokines and reactive oxygen and nitrogen species. These proinflammatory cytokines activate astrocytes and trigger neurodegenerative diseases. In this work, we chose to address the mechanistic aspects of alpha-crystallin's protective function in inflammation-triggered neurotoxicity in mice. Alpha-crystallin, a lens structural protein, comprising alpha-A and alpha-B subunits is an ubiquitous molecular chaperone, which have been shown to reduce reactive oxygen species (ROS) production and enhance cellular glutathione level in the acute inflammation-induced mice. Results show that the proinflammatory cytokines such as interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) were significantly high (P<0.05) in the plasma, liver, cortex and hippocampus of inflammation-induced mice when compared to control. Alpha-crystallin pretreatment prevents inflammation-induced cytokines and NO production. In addition, a significant (P<0.05) reduction of dopamine (DA), 5-hydroxytryptamine (5-HT) and norepinephrine (NE) was also observed in the inflammation-induced mice. Nevertheless, their metabolites, such as 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) increased significantly (P<0.05) as compared to control. The results indicate that alpha-crystallin pretreatment controls the inflammation-induced DA, 5-HT and NE catabolism and suggest that alpha-crystallin has the potential to act as an anti-inflammatory agent in the neuroprotective processes.
Masilamoni
J Gunasingh
JG
Bio-Organic and Neurochemistry Laboratory, Central Leather Research Institute, Adyar, Chennai 600020, Tamil Nadu, India.
Vignesh
S
S
Kirubagaran
R
R
Jesudason
E Philip
EP
Jayakumar
R
R
D000704:Analysis of Variance; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004563:Electrochemistry / Q000379:methods; D007249:Inflammation / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000378:metabolism; D010949:Plasma / Q000187:drug effects / Q000378:metabolism; D038201:alpha-Crystallins / Q000008:administration & dosage*
D001679:Biogenic Amines; D018696:Neuroprotective Agents; D038201:alpha-Crystallins; D009569:Nitric Oxide