Decreased Mcl-1 protein level in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a well-known neurotoxicant that can selectively destroy dopaminergic neurons and MPTP-treated animals are often used as models for studying aspects of Parkinson's disease (PD). While apoptosis has been suggested as a possible mechanism underlying MPTP-induced cell death and several apoptosis-associated proteins have been implicated in MPTP-animal models, relevant information regarding the possible involvement of Mcl-1 (myeloid cell leukemia 1) protein is missing. Mcl-l is an important member of the Bcl-2 family that is thought to be a highly regulated controller of cell death and survival. However, the expression level of Mcl-1 in response to MPTP-treatment has not been examined in any area of the brain previously. In the present study, an acute MPTP treatment regimen was utilized with male C57BL/6 mice (10 mg/kg i.p. injections, 4 times with 2 h intervals) and several protein markers were examined 24-h after the initial injection. Dramatic decreases in the immunoreactivities of tyrosine hydroxylase and dopamine transporters were observed. Western-blot analysis and immunocytochemical labeling demonstrated an MPTP-induced decrease in Mcl-1 protein levels in the striatum. In addition, the two proteins BAX and ERK, both of which are also involved in apoptosis signaling, were examined. While the total BAX levels showed no significant difference between the control and MPTP-treated groups, levels of phosphorylated ERK were significantly increased following MPTP-treatment. Since Mcl-1 is an anti-apoptotic protein, down-regulation of Mcl-1 following MPTP-treatment would be expected to lead to increased apoptotic activities processes, leading to increased neurodegeneration.