Organophosphorus Compound-Induced Modification of SH-SY5Y Human Neuroblastoma Mitochondrial Transmembrane Potential

Carlson, Kent; Ehrich, Marion

doi:10.1006/taap.1999.8741

Cited by 77 publications

(38 citation statements)

References 48 publications

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“…The organophosphorus compound, parathion, can partition into mitochondrial membranes and has previously been shown to induce mitochondrial hyperpolarization in human neuroblastoma cells (34). As shown in Fig.…”

Section: Il-3 Withdrawal Increases Mitochondrial Membrane Potentialmentioning

confidence: 88%

“…To address this, we induced mitochondrial hyperpolarization with the organophosphorus compound, parathion (34). Parathion induced cell death, with mitochondrial disruption, but this death did not require the translocation of Bax or the activation of caspases and was not protected by Bcl-2; thus, mitochondrial hyperpolarization per se could lead to cell death, independent of the apoptotic cascade (Fig.…”

Section: Il-3 Withdrawal Increases Mitochondrial Membrane Potentialmentioning

confidence: 99%

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Interleukin-3 Withdrawal Induces an Early Increase in Mitochondrial Membrane Potential Unrelated to the Bcl-2 Family

Khaled

Reynolds

Young

et al. 2001

Journal of Biological Chemistry

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Cytokines such as interleukin-3 (IL-3) promote the survival of hematopoietic cells through mechanisms that are not well characterized. Withdrawal of IL-3 from an IL-3-dependent pro-B cell line induced early stressrelated events that preceded cell death by more than 40 h. Intracellular pH rose above pH 7.8, peaking 2-3 h post-IL-3 withdrawal, and induced a transient increase in mitochondrial membrane potential (⌬⌿ m ) detected using several different dyes. Similar events were observed following IL-7 withdrawal from a different dependent cell line. Bcl-2, Bax, and caspases were unrelated to these early events. Intracellular alkaline pH inhibited the mitochondrial import of ADP, which would limit ATP synthesis. Total cellular ATP sharply declined during this early period, presumably as a consequence of suppressed ADP import. This was followed by an increase in reduced pyridine nucleotides. The transient increase in ⌬⌿ m was blocked by oligomycin, an inhibitor of F 0 F 1-ATPase that may have undergone reversal caused by the abnormal ADP-ATP balance within mitochondria. These findings suggest a novel sequence of early events following trophic factor withdrawal in which alkaline pH inhibits ADP import into mitochondria, reversing the F 0 F 1-ATPase, which in turn consumes ATP and pumps out protons, raising ⌬⌿ m .

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Section: Il-3 Withdrawal Increases Mitochondrial Membrane Potentialmentioning

confidence: 88%

Section: Il-3 Withdrawal Increases Mitochondrial Membrane Potentialmentioning

confidence: 99%

Interleukin-3 Withdrawal Induces an Early Increase in Mitochondrial Membrane Potential Unrelated to the Bcl-2 Family

Khaled

Reynolds

Young

et al. 2001

Journal of Biological Chemistry

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“…Nuclear and genetic changes have been described in a variety of in vitro [1][2][3][4][5][6][7] and in vivo [8][9][10] models following exposure to OP compounds. A variety of other intracellular targets for OP compounds, such as mitochondria [11,12], enzymes [13,14], the cytoskeleton and f-actin [15,16], and the plasma membrane [17], have also been described. Although these publications have described potential events leading to cell cycle disruption, they have not fully elaborated on the stage or extent of cell cycle affected.…”

Section: Introductionmentioning

confidence: 98%

Distribution of SH‐SY5Y human neuroblastoma cells in the cell cycle following exposure to organophosphorus compounds

Carlson

Ehrich

2008

J Biochem & Molecular Tox

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The current study investigated the relationship of the cell cycle phase (as G(0)/G(1), S, and G(2)/M) and cytotoxicity (as sub-G(1) DNA) to determine whether alterations in cell replication were associated with organophosphate (OP) compound induced cytotoxicity. Results demonstrated that, overall, OP compound--induced cell cycle changes were variable and depended on the OP compound, exposure concentration, and temporal relationship to cytotoxicity. Noncytotoxic OP compound treatments substantially decreased the percentage of cells in S phase of the cell cycle when compared to controls. A corresponding increase was seen in the percent of cells in G(0)/G(1) phase of the cell cycle. In the precytotoxic interval of exposure, most cytotoxic OP compound treatments substantially decreased the percentage of cells in G(2)/M phase of the cell cycle. Corresponding increases were seen primarily in G(0)/G(1) phase cells. Effects on cells in S stage of the cell cycle varied with the OP compound. In the during cytotoxic interval of exposure, most cytotoxic OP compound treatments substantially increased the percentage of cells in S phase of the cell cycle. A corresponding decrease in the percent of cells in G(0)/G(1) stage of the cell cycle was observed. Furthermore, treatments either increased or decreased the percentage of cells in G(2)/M phase of the cell cycle when compared to controls, with decreases more likely with the most cytotoxic OP compound exposures. Overall, the in vitro data suggest that exposure to OP compounds can alter the cell cycle status of SH-SY5Y neuroblastoma cells depending on compound, concentration, and interval from initial exposure. Changes in cell cycle, however, did not differentiate between OP compounds that are known for their ability to acutely inhibit acetylcholinesterase versus those inducing type I and type II delayed neurotoxicity.

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“…The inhibitory action on mitochondrial oxidative phosphorylation may explain physiological changes (Gupta et al, 1994;Carlson and Ehrich, 1999) not related to inhibition of the cholinergic system. Therefore, the correlation between alterations in membrane organization and function provides novel insights to the understanding of the molecular mechanisms of ethylazinphos toxicity in particular and of insecticides in general.…”

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confidence: 99%

Ethylazinphos Interaction with Membrane Lipid Organization Induces Increase of Proton Permeability and Impairment of Mitochondrial Bioenergetic Functions

Videira

Antunes-Madeira

Madeira

2001

Toxicology and Applied Pharmacology

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Ethylazinphos increases the passive proton permeability of lipid bilayers reconstituted with dipalmitoylphosphatidylcholine (DPPC) and mitochondrial lipids. A sharp increase of proton permeability is detected at insecticide/lipid molar ratios identical to those inducing phase separation in the plane of DPPC bilayers, as revealed by differential scanning calorimetry (DSC). Ethylazinphos progressively depresses the transmembrane potential (⌬⌿) of mitochondria supported by piruvate/malate, succinate, or ascorbate/TMPD. Additionally, a decreased depolarization induced by ADP depends on ethylazinphos concentration, reflecting a phosphorylation depression. This loss of phosphorylation is a consequence of a decreased ⌬⌿. A decreased respiratory control ratio is also observed, since ethylazinphos stimulates state 4 respiration and inhibits ADPstimulated respiration (state 3). Ethylazinphos concentrations up to 100 nmol/mg mitochondrial protein increase the rate of state 4 together with a decrease in ⌬⌿, without significant perturbation of state 3 and carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP)-uncoupled respiration. For increased insecticide concentrations, the state 3 and FCCP-uncoupled respiration are inhibited to approximately the same extent. The perturbations are more pronounced when the energization is supported by pyruvate/ malate and less effective when succinate is used as substrate. The present data, in association with previous DSC studies, indicate that ethylazinphos, at concentrations up to 100 nmol/mg mitochondrial protein, interacts with the lipid bilayer of mitochondrial membrane, changing the lipid organization and increasing the proton permeability of the inner membrane. The increased proton permeability explains the decreased oxidative phosphorylation coupling. Resulting disturbed ATP synthesis may significantly underlie the mechanisms of ethylazinphos toxicity, since most of cell energy in eukaryotes is provided by mitochondria. © 2001 Academic PressKey Words: ethylazinphos; membrane organization; proton permeability; mitochondrial respiration; transmembrane potential; oxidative phosphorylation.The two major components of the biological membranes are lipids and proteins. Together they determine the organization and function of membranes. These dynamic and versatile barriers are, in turn, involved in most cellular functions (Kinnunen, 1991). A large number of drugs with different chemical structures and pharmacological effects are able to accumulate in membrane lipid domains, changing their organization and physical properties and, consequently, their function (Sikkema et al., 1995;Mouritsen and Jørgensen, 1998), since the preservation of an exact degree of organization is essential for most membrane activities (Eze, 1990;Mouritsen and Jørgensen, 1998;Williams, 1998). Examples of the above compounds include anesthetics, calcium channel blocking drugs, alcohols, and insecticides (Makriyannis et al., 1986;Bae et al., 1989;Barry and Gawrisch, 1994;Mavromoustakos et al., 1995;Antunes-Madeira...

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Organophosphorus Compound-Induced Modification of SH-SY5Y Human Neuroblastoma Mitochondrial Transmembrane Potential

Cited by 77 publications

References 48 publications

Interleukin-3 Withdrawal Induces an Early Increase in Mitochondrial Membrane Potential Unrelated to the Bcl-2 Family

Interleukin-3 Withdrawal Induces an Early Increase in Mitochondrial Membrane Potential Unrelated to the Bcl-2 Family

Distribution of SH‐SY5Y human neuroblastoma cells in the cell cycle following exposure to organophosphorus compounds

Ethylazinphos Interaction with Membrane Lipid Organization Induces Increase of Proton Permeability and Impairment of Mitochondrial Bioenergetic Functions

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