Disease relevance of 370-86-5

• Monensin and FCCP inhibit the intracellular transport of alphavirus membrane glycoproteins [1].
• We found that FCCP-uncoupling in situ had a relatively small effect on ATP depletion during ischemia in rabbit hearts, that it dramatically accelerated ATP depletion in ischemic rat hearts, and that it had an intermediate effect on ATP depletion in ischemic pigeon hearts [2].
• Neither activation of the respiratory burst nor phagocytosis of either latex particles or serum-opsonized Staphylococcus aureus was affected by the addition of FCCP or oligomycin [3].
• Endothelial cells exposed to relative hypoxia or the mitochondrial inhibitors rotenone, antimycin A, or FCCP show loss of mitochondrial membrane potential [4].
• Exposure to FCCP alone (1-10 microM, 10 min), however, failed to produce any toxicity [5].

Psychiatry related information on 370-86-5

• The FCCP effect on calcium storage may be related to mitochondrial dysfunction in Alzheimer disease, which might result in ineffective buffering of cytosolic calcium that leads to mitogen-activated protein kinase activation and subsequent protein phosphorylations [6].
• FCCP (0.31 microM), at 10 minutes' incubation time, enhanced the efflux of 14C-5HT to a significantly higher extent from platelets of patients with bipolar depression than from platelets of control subjects [7].

High impact information on 370-86-5

• FCCP also caused MEL cell mitochondria to release calcium into the cytoplasm [8].
• Addition of either antimycin (respiratory chain inhibitor) or FCCP (respiratory chain uncoupler) prevented increased O2-. scavenging [9].
• However, evaluation of the source of these observed potential changes revealed that the FCCP-insensitive fraction of the overall potential, delta psi P, (representing the plasma membrane potential), was not affected [10].
• Cells were protected against both toxins with antiserum as well as with agents like NH4Cl, procaine, and the ionophores monensin, FCCP, and CCCP, which increase the pH of intracellular vesicles [11].
• FCCP (carbonylcyanide-p-trifluoromethoxyphenylhydrazone), a potent uncoupler of oxidative phosphorylation, induces the complete disruption of cellular microtubules [12].

Chemical compound and disease context of 370-86-5

• During hypoxia, an increase in cytoplasmic ROS and glutathione S-transferase activity occurred, suggesting changes in intracellular redox state, mimicked with rotenone or FCCP but inhibited by antimycin A [4].
• During mitochondrial inhibition (due to exposure to carbonyl cyanide p-trifluromethoxyphenyl hydrazone (FCCP) and oligomycin), rises in [Ca2+]i (observed in Ca2+-free perfusate) evoked by hypoxia or by BK, were significantly enhanced, and hypoxia always evoked responses [13].
• The response to anoxia was occluded by concurrent application of FCCP, suggesting that the Ca2+ originates from the same pool in each case [14].
• 4. Simultaneous recordings of membrane current, DeltaPsim and [Ca2+]i revealed the sequence of events in response to impaired mitochondrial function (CN, FCCP or anoxia): DeltaPsim depolarized, followed rapidly by an increase in [Ca2+]i followed in turn by the outward current [15].
• Tolcapone and FCCP were shown to be toxic to human neuroblastoma SH-SY5Y cells and caused a profound reduction in ATP synthesis [16].

Biological context of 370-86-5

• It is concluded that ATP produced by glycolysis is hydrolyzed by the membrane ATPase to generate a delta pH and that FCCP stimulates ATP hydrolysis by ATPase and collapses the proton gradient [17].
• On the other hand, thiocyanate or FCCP, at varying concentration, produced a dose-related collapse of the membrane potential and had no effect upon the transmembrane proton gradient [18].
• The reduction of the potential by either decreasing the light intensity or by adding increasing concentrations of the ionophore carbonylcyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) revealed a marked inhibition of the cytochrome b(6) oxidation rate (10-fold) without substantial modifications of cytochrome f oxidation kinetics [19].
• However, FCCP inhibited chemotaxis at concentrations that paralleled disruption of mitochondrial membrane potential [3].
• TG- or FCCP-induced caspase-3 activation occurred at the same time, but the cell death induced by TG was delayed [20].

Anatomical context of 370-86-5

• A further analysis of this effect on BHK21 cells has shown that a decrease in the number of microtubules can be observed 15 min after adding FCCP and there is complete disruption after 60 min [12].
• We have investigated in rat pheochromacytoma PC12 cells the activation of the mitogen-activated protein kinases ERK1 and ERK2 by the mitochondrial uncoupler carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) [6].
• The FCCP-sensitive store slows both the rise in [Ca2+]i during stimulation (apparently by accumulating Ca2+ from the cytosol) and the recovery following stimulation (by releasing the accumulated Ca2+ into the cytosol) [21].
• Rottlerin increased the QO2 of isolated rat liver mitochondria to a level similar to that produced when oxidative phosphorylation was initiated by ADP or when mitochondria were uncoupled by carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) [22].
• K(ir)2.2 and K(ir)2.3 currents perfusion of inside-out patches from FCCP-treated oocytes [23].

Associations of 370-86-5 with other chemical compounds

• Regrowth of microtubules was initiated 30 min after removal of FCCP, in marked contrast with the rapid reversion observed when microtubules are disrupted by nocodazole [12].
• When the cells were previously treated with DCCD, FCCP collapsed the delta pH while the NTP levels remained high [17].
• Upon depolarization by the addition of fully uncoupling concentrations of carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) mitochondria favor a high MTP "open" probability and rapidly undergo a process of osmotic swelling following sucrose diffusion toward the matrix [24].
• Linoleic acid decreases the yield of oxidative phosphorylation in a concentration-dependent manner by a pure protonophoric process like that in the presence of FCCP [25].
• We observed that 10 microm tamoxifen in the presence of estradiol affected mitochondria significantly by decreasing FCCP-stimulated respiration, state 3 of respiration, respiratory control ratio, and ADP depolarization and increasing the lag phase of repolarization [26].

Gene context of 370-86-5

• RESULTS: Thermogenesis increased after exposing yeast to the mitochondrial uncoupler, FCCP, or transforming the cells with UCP2 [27].
• We also showed that oligomycine which inhibits ATP synthase and FCCP, which uncouples respiration also led to dose-dependent inhibition of NF-kappa B activation by H2O2 [28].
• Moreover, the effects of FCCP were independent of alterations in total cellular APP levels or APP maturation, and the concentrations used did not alter either cellular ATP levels or cell viability [29].
• Novel effects of FCCP [carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone] on amyloid precursor protein processing [29].
• Exposure of islet cells to proinflammatory cytokines IL-1beta, TNF-alpha, and IFN-gamma, or to the mitochondrial uncoupler FCCP resulted in disruption of the mitochondrial membrane potential ((m)) and beta-cell death [30].

Analytical, diagnostic and therapeutic context of 370-86-5

• SDS-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of the microtubules polymerized in vitro in the presence of FCCP showed a reduced amount of high mol. wt. proteins, mainly MAP 2, associated with them [12].
• A titration with FCCP reveals that discrete subpopulations of mitochondria with different gating potentials for MTP opening may exist, since increasing concentrations of FCCP increase the fraction of mitochondria undergoing osmotic swelling [24].
• Furthermore, significant reduction of fluorescence intensity in the cells stained with 2.0 microM DiOC(6)(3) was observed after treatment with 10 microM FCCP for 30 min [31].
• The mitochondrial uncoupling agent carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) raised [Ca2+]m in unstimulated cells, but lowered it in cells subjected to electrical stimulation at 2 Hz or more, to partial Na+ replacement, or to the alkaloid veratridine [32].
• In addition, mitochondrial state was monitored using confocal microscopy to record mitochondrial potential (TMRM) and redox state (NADH) during FCCP and diazoxide treatment [33].

References