Cholesterol-Rich Plasma Membrane Submicrodomains Can Be a Major Extram- itochondrial Source of Reactive Oxygen Species in Partially Depolarized Mature Cerebellar Granule Neurons in Culture

doi:10.17303/jnnd.2019.5.204

Abstract

Highlights

Oxidative stress induced by excessive production of reactive oxygen and nitrogen species can elicit neuronal cell death and brain neurodegeneration
We have shown that lipid rafts nanodomains of mature cerebellar granule neurons (CGN) contain most of the neuronal nitric oxide synthase and of cytochrome b5 reductase isoform 3 (Cb5R3), which is the component of neuronal synaptic plasma membrane vesicles that generates superoxide anion upon stimulation by cytochrome c
We have shown that dysregulation of cytochrome b5 reductase (Cb5R) associated with plasma membrane lipid rafts sub-microdomains is largely responsible for the overshot of superoxide anion observed at the onset of CGN apoptosis induced by 5 mM potassium concentration in the extracellular medium [16,22]

Summary

Introduction

Oxidative stress induced by excessive production of reactive oxygen and nitrogen species can elicit neuronal cell death and brain neurodegeneration. This has been shown during last 20 years with neuronal cultures in vitro [1,2,3], with animal models of neurodegenerative diseases [4,5] and brain insults like transient ischemia [6,7], and in human brains after brain stroke [8] or affected by major neurodegenerative diseases [2,9,10,11,12]. The addition of superoxide dismutase (SOD) to the extracellular medium of CGN cultures quenches more than 90% of this ROS overshot and blocks the apop-

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Conclusion