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.