» Articles » PMID: 10797557

Alterations of Intracellular Calcium Homeostasis and Mitochondrial Function Are Involved in Ruthenium Red Neurotoxicity in Primary Cortical Cultures

Overview
Journal J Neurosci Res
Specialty Neurology
Date 2000 May 8
PMID 10797557
Citations 9
Authors
Affiliations
Soon will be listed here.
Abstract

Ruthenium red (RR) is a polycationic dye that induces neuronal death in vivo and in primary cultures. To characterize this neurotoxic action and to determine the mechanisms involved, we have analyzed the ultrastructural alterations induced by RR in rat cortical neuronal cultures and measured its effect on cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) and on mitochondrial function. RR produced a dose-dependent, progressive disruption of neurites and plasma membrane of neuronal somata after 8-24 hr of incubation. RR caused also an elevation of both the basal [Ca(2+)](i) and its maximal levels after K(+) depolarization. Mitochondrial oxidative function, assessed by reduction of 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and by changes in dihydrorhodamine-123 fluorescence, was significantly diminished after treatment with RR, both in cultured neurons and in isolated brain mitochondria. La(3+) did not prevent but rather potentiated RR-induced cell death. Glutamate receptor antagonists also failed to prevent RR neurotoxicity. Apoptotic electron microscope images were not observed, and protein synthesis inhibitors did not show any protective effect. It is concluded that RR penetrates neurons and that its neurotoxic damage probably is due to intracellular Ca(2+) dishomeostasis and disruption of mitochondrial oxidative function. These results enhance our understanding of the intracellular mechanisms underlying neuronal death.

Citing Articles

Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19.

Loh D, Reiter R Int J Mol Sci. 2022; 23(15).

PMID: 35897696 PMC: 9368024. DOI: 10.3390/ijms23158122.


The cell-permeable mitochondrial calcium uniporter inhibitor Ru265 preserves cortical neuron respiration after lethal oxygen glucose deprivation and reduces hypoxic/ischemic brain injury.

Novorolsky R, Nichols M, Kim J, Pavlov E, Woods J, Wilson J J Cereb Blood Flow Metab. 2020; 40(6):1172-1181.

PMID: 32126877 PMC: 7238378. DOI: 10.1177/0271678X20908523.


Zn entry through the mitochondrial calcium uniporter is a critical contributor to mitochondrial dysfunction and neurodegeneration.

Ji S, Medvedeva Y, Weiss J Exp Neurol. 2019; 325:113161.

PMID: 31881218 PMC: 6957126. DOI: 10.1016/j.expneurol.2019.113161.


Mitochondrial Zn Accumulation: A Potential Trigger of Hippocampal Ischemic Injury.

Ji S, Medvedeva Y, Wang H, Yin H, Weiss J Neuroscientist. 2018; 25(2):126-138.

PMID: 29742958 PMC: 6730558. DOI: 10.1177/1073858418772548.


Zn-induced disruption of neuronal mitochondrial function: Synergism with Ca, critical dependence upon cytosolic Zn buffering, and contributions to neuronal injury.

Ji S, Weiss J Exp Neurol. 2018; 302:181-195.

PMID: 29355498 PMC: 5849513. DOI: 10.1016/j.expneurol.2018.01.012.