Mechanisms of rapid reactive oxygen species generation in response to cytosolic Ca2+ or Zn2+ loads in cortical neurons

PloS One
Aaron ClausenJ H Weiss

Abstract

Excessive "excitotoxic" accumulation of Ca(2+) and Zn(2+) within neurons contributes to neurodegeneration in pathological conditions including ischemia. Putative early targets of these ions, both of which are linked to increased reactive oxygen species (ROS) generation, are mitochondria and the cytosolic enzyme, NADPH oxidase (NOX). The present study uses primary cortical neuronal cultures to examine respective contributions of mitochondria and NOX to ROS generation in response to Ca(2+) or Zn(2+) loading. Induction of rapid cytosolic accumulation of either Ca(2+) (via NMDA exposure) or Zn(2+) (via Zn(2+)/Pyrithione exposure in 0 Ca(2+)) caused sharp cytosolic rises in these ions, as well as a strong and rapid increase in ROS generation. Inhibition of NOX activation significantly reduced the Ca(2+)-induced ROS production with little effect on the Zn(2+)- triggered ROS generation. Conversely, dissipation of the mitochondrial electrochemical gradient increased the cytosolic Ca(2+) or Zn(2+) rises caused by these exposures, consistent with inhibition of mitochondrial uptake of these ions. However, such disruption of mitochondrial function markedly suppressed the Zn(2+)-triggered ROS, while partially attenuating the Ca(2+)-triggere...Continue Reading

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Citations

Oct 4, 2014·Environmental Science & Technology·Qingyang LiuMeigen Zhang
Oct 11, 2015·Biochemical and Biophysical Research Communications·Jinbo Liu, Lijian Du
May 6, 2015·Neurobiology of Disease·Alberto Granzotto, Stefano L Sensi
May 18, 2016·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Heidi HsiehMary Beth Genter
May 11, 2018·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Sung G JiJohn H Weiss
May 11, 2018·Oxidative Medicine and Cellular Longevity·Sung Ryul Lee
May 2, 2018·International Journal of Molecular Sciences·Gloria Salazar
Apr 7, 2020·Platelets·M E Lopes-PiresN Pugh
Oct 6, 2020·Frontiers in Neuroscience·Jiejie Wang, Raymond A Swanson
Dec 17, 2020·Frontiers in Molecular Neuroscience·Alberto GranzottoStefano L Sensi
Nov 17, 2020·Frontiers in Neuroscience·Dennis W Choi
May 6, 2021·Biomedicines·Hilary Y LiuElias Aizenman

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Methods Mentioned

BETA
Assay

Software Mentioned

Zeiss LaserSharp 2000
MetaFluor

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