| Abstrakt: |
Neuroinflammation is one of the causal components in the progress of neurodegenerative disorders. Proinflammatory imbalance induces both cellular response against to stress factor and excessive production of reactive species. Furthermore, inflammation in neural tissue cells can initiate the decline in the cell viability. The models of proinflammatory reactivity are convenient tool to elucidate the molecular mechanism of neural tissue cells abnormality. Lipopolysaccharide (LPS) is confirmed as universal initiator of inflammation in various cell types including glial cells. Astrocytes are the largest population of glial cells in the brain. In a like manner to other cell types astrocytes can produce inflammatory factors as result of the damaging agent effects as well as response against LPS stimulation. Besides, various stimuli including LPS induce universal cellular response in astrocytes, which is called astrogliosis. Most common sign of astrocyte reactivity is upregulation of glial fibrillary acidic protein (GFAP) expression. Astrocyte reactivity is accompanied by signaling pathways activation, metabolic energy spending and increased mitochondrial productivity. All aforementioned dysregulations are associated with ROS generation, upregulation in cytokines production and excessive growth of cell reactivity. Moreover, astrogliosis accompanied by the interaction between oxidative stress and proinflammatory changes. Therefore, astrogliosis to both brain tissue repair and neural tissue cells damaging. Several transcriptional factors and DNA repair machinery are the sensors of oxidative damages and could be involved in glial initiated disturbance. On the other side, they are promising targets to regulate astrogliosis and to prevent brain cell injury caused by neuroinfammation. Curcumin is a well-know n antioxidant and anti-inflammatory agent. Curcumin is hydrophobic polyphenol and this feature limits its bioavailability. However, current technology lets to synthesise soluble curcumin derivatives that is principal to apply this polyphenol as cytoprotective agent. In the presented study, we tested low doses of water-soluble curcumin to determine glioprotective effect against both neuroinflammation and oxidative stress in LPS-stimulated primary rat astrocytes. The expression of GFAP, NF-kB and PARP-1 was assessed as cytoskeleton, transcriptional and DNA repair marker correspondingly in astrocyte reactivated with LPS. Obtained results have shown that LPS exposure induced dose-dependent decline in cell viability, upregulation GFAP, NF-kB and downregulation of PARP-1 expression and the growth ROS production. PARP-1 fragmentation was detected in respect 80 kDa that reflects partpanatos initiation. Contrary, all aforementioned indexes were improved in LPS-reactivated astrocytes exposed to soluble curcumin (2-10 µM). Moreover, soluble curcumin exposure prevented a lack of cell viability of reactive astrocytes. Dose-depended glioprotective effects of soluble curcumin were determined for all measured parameters with statistically significant differences (P<0.05). Observed data evidence that soluble curcumin inhibits astrogliosis and develops glioprotective effect through its antioxidant and anti-parthanatos activities. The functional interaction between PARP and glial cytoskeleton could be one of promising target of natural polyphenols to develop glioprotective effects. [ABSTRACT FROM AUTHOR] |
