The mechanism of action of MPTP-induced neuroinflammation and its modulation by melatonin in rat astrocytoma cells, C6.
The 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine (MPTP) induces reactive astrogliosis, the cellular manifestation of neuroinflammation, in various models of Parkinson's disease (PD), but its mechanism of action on astrocytes is not understood. The effect of melatonin on MPTP-induced neuroinflammation in astrocytes is also not known. The present study demonstrated that MPTP treatment of rat astrocytoma cells, C6 for 24 h significantly increased nitrative and oxidative stress and intracellular calcium (Ca2++) level. MPTP also activated phosphorylated p38 mitogen activated protein kinase (P-p38 MAPK) and up-regulated expressions of inflammatory proteins. Moreover, MPTP modulated mRNA expressions of pro-inflammatory cytokine genes via activating nuclear factor kappa-B (NF-kB) translocation. Treatment of melatonin with MPTP reversed all these MPTP-induced changes. Study with deprenyl demonstrates that MPTP is inducing neuroinflammation in astrocytoma cells. The present findings elucidated the molecular mechanism of MPTP-induced neuroinflammation and its modulation by melatonin in astrocytoma cells (C6).
Niranjan
Rituraj
R
Division of Pharmacology, Central Drug Research Institute, CSIR, Lucknow, India.
Nath
Chandishwar
C
Shukla
Rakesh
R
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001254:Astrocytoma / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008550:Melatonin / Q000494:pharmacology*; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
D016328:NF-kappa B; D009498:Neurotoxins; D017382:Reactive Oxygen Species; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D048051:p38 Mitogen-Activated Protein Kinases; D008550:Melatonin