[P38MAPK pathway regulates COX-2 and caspase-3 expression in a mouse model of Parkinson disease]

Nan Fang Yi Ke Da Xue Xue Bao. 2009 Oct;29(10):2010-3, 2017.
[Article in Chinese]

Abstract

Objective: To investigate the effect of p38 mitogen-activated protein kinase (p38MAPK) on the expression of COX-2 and caspase-3 in the substania nigra (SN) of mice with MPTP-induced Parkinson disease (PD).

Methods: C57BL/CN mice were treated with MPTP to prepare a subacute PD model, and their behavioral changes following the treatment were observed. Immunohistochemistry and Western blotting were performed to detect the expression of tyrosine hydroxylase (TH), COX-2 and phosphorylation of P38MAPK in the SN and their changes following treatment with SB203580, a specific inhibitor of P38MAPK.

Results: The 7-day model group showed typical symptoms of PD with decrements of TH-positive neurons and TH protein level in the SN of the midbrain by about 65% and 75%, respectively (P<0.01). In the 3-day model group, the COX-2-, caspase-3- and phosphorylated P38MAPK-immunoreactive cells and their protein levels in the SN increased markedly with obvious loss of TH-positive neurons. Administration of SB203580 obviously lessened the above changes (P<0.01).

Conclusion: P38MAPK regulates the inflammation and apoptosis in the SN of the mouse model of subacute PD, and SB203580 may provide some neuroprotective effect.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 3 / genetics
  • Caspase 3 / metabolism*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Parkinson Disease / metabolism*
  • Signal Transduction
  • Substantia Nigra / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • p38 Mitogen-Activated Protein Kinases
  • Casp3 protein, mouse
  • Caspase 3