Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.64 (
MPP
)
1,876
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The toxicity caused by cell exposure to 1-methyl-4-phenylpyridinium ion (
MPP
(+)) is a useful model in the study of Parkinson's disease (PD). However, the exact molecular mechanisms triggered by
MPP
(+) in cell death are currently unclear. In the present research, we show that exposure to
MPP
(+) induce the cell death of neuroblastoma-derived dopaminergic B65 cells, which is not reversed by the widely known caspase inhibitor Z-VAD fmk or by calpain inhibition. Likewise, when B65 cells were treated with
MPP
(+), the DNA damage pathway that involves p53 was activated, and cells were arrested in the G(2)/M phase of the cell cycle. Interestingly,
MPP
(+) has two effects on the expression of cell cycle-related proteins. It increases the content of cyclins A, E, cdk2 and the phosphorylated form of pRb (serine 780). However,
MPP
(+) 5mM decreased the expression of cyclin D1, B1 and cdk4. The decrease in the expression of
cyclin B1
may be related to the arrest of cells observed in the G(2)/M phase of cell cycle. The increase in S phase cell cycle proteins and retinoblastoma protein phosphorylation was an unexpected result. As the antioxidant trolox attenuated the process of cell loss and changes in the cell cycle, as measured by flow cytometry, we concluded that oxidative stress was involved in the effects of
MPP
(+) in this cell line. In summary, the present work characterizes the molecular changes involved in damage caused by
MPP
(+) in B65 cells, and highlights the effects of
MPP
(+) on molecules involved in the control of cell cycle progression.
...
PMID:Effects of MPP+ on the molecular pathways involved in cell cycle control in B65 neuroblastoma cells. 2008 Jan 85
