Inhibition of store-operated calcium entry attenuates MPP(+)-induced oxidative stress via preservation of mitochondrial function in PC12 cells: involvement of Homer1a

PloS One
Xia LiZhou Fei

Abstract

The process of store-operated calcium entry (SOCE), whereby the release of intracellular Ca(2+) from endoplasmic reticulum (ER) activates Ca(2+) influx channels in the plasma membrane, has been demonstrated to impact a diverse range of cell functions. In the present study, we investigated the potential protective effect of SOCE inhibition against 1-methyl-4-phenylpyridinium (MPP(+)) injury by using pharmacological antagonists or specific small interfering RNA (siRNA) in PC12 cells. The results showed that both antagonists (15 μM MRS-1845 and 50 μM ML-9) and stromal interacting molecule-1 (STIM1) targeted siRNA (Si-STIM1) significantly increased cell viability, decreased apoptotic cell death and reduced intracellular reactive oxygen species (ROS) production and lipid peroxidation in MPP(+) injured PC12 cells. SOCE inhibition also prevented MPP(+) induced mitochondrial dysfunction and activation of mitochondrial related apoptotic factors, while had no effect on mitochondrial biogenesis. Moreover, inhibition of SOCE by antagonists and siRNA increased the expression levels of Homer1a mRNA and protein, and knockdown of Homer1a expression by specific siRNA partly reversed the protective effects induced by SOCE inhibition in PC12 cell...Continue Reading

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Citations

Nov 9, 2016·Frontiers in Cellular Neuroscience·Joanna Gruszczynska-BiegalaJacek Kuznicki
Dec 13, 2016·Pharmaceutical Biology·Se-Myeong CheonDong Seok Cha
Jan 30, 2015·Neurotoxicity Research·Juan Segura-Aguilar, Richard M Kostrzewa
Dec 21, 2018·World Journal of Biological Chemistry·Carlos Pascual-CaroFrancisco Javier Martin-Romero
Apr 7, 2018·Frontiers in Molecular Neuroscience·Agnese SecondoDiana Amantea
Feb 28, 2019·Frontiers in Neuroscience·Marco Tulio Núñez, Cecilia Hidalgo
Jan 12, 2021·Frontiers in Molecular Neuroscience·Karolina Serwach, Joanna Gruszczynska-Biegala
Apr 4, 2021·International Journal of Molecular Sciences·Anastasiia BohushAnna Filipek
May 18, 2021·Frontiers in Pharmacology·W Zhong, N A Darmani

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Methods Mentioned

BETA
protein assay
ELISA
transfection
fluorescence microscopy
Assay
fluorescence assay
PCR
gene knockdown
MDA

Software Mentioned

SPSS
Image J

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