Abstract: Objective To investigate the role of calcium dyshomeostasis in 1-methyl-4-phenylpyridinium ion (MPP+ )-induced
apoptosis of human neuroblastoma SH-SY5Y cells. Methods The viability of SH-SY5Y cells exposed to varying concentrations
of MPP + was assessed using MTT colorimetric assay, and MPP +-induced cell apoptosis was detected with hoechst 33342
staining and Annexin V+ PI assay. Western blotting and rhodamine 123 staining were employed to examine the changes in
cellular poly(ADP-ribose)polymerase (PARP) protein expression and mitochondrial membrane potential in response to MPP+
exposure. The effects of ruthenium red and/or MPP + on calcium concentration in the cytoplasm, mitochondria and
endoplasmic reticulum were evaluated using confocal microscopy. Results MPP+ induced apoptosis and caused reduced cell
viability and mitochondrial membrane potential in SH-SY5Y cells. The cells exposed to MPP + showed a lowered calcium
concentration in the cytoplasm and endoplasmic reticulum and an increased mitochondrial Ca2 + uptake. Ruthenium red
rescued MPP+-induced apoptosis and mitochondrial membrane potential reduction, reduced PARP cleavage, and inhibited the
increase of mitochondrial matrix free Ca2 + in the cells exposed to MPP+ . Conclusion Mitochondrial calcium overload plays an
important role in MPP+-induced apoptosis of SH-SY5Y cells, which is closely associated with dysregulation of intracellular Ca2+
homeostasis.