Methotrexate: Studies on cellular metabolism. II—Effects on mitochondrial oxidative metabolism and ion transport

  title={Methotrexate: Studies on cellular metabolism. II—Effects on mitochondrial oxidative metabolism and ion transport},
  author={Noriko Yamamoto and L C Lopes and Annibal P. Campello and M L Kl{\"u}ppel},
  journal={Cell Biochemistry and Function},
Effects of methotrexate (MTX) on mitochondrial oxidative metabolism and ion transport were studied. MTX decreases the membrane potential (Δψ) upon energization of the mitochondrial membrane by NAD+‐linked substrates and decreases the amplitude and velocity of swelling induced by glutamate and α‐ketoglutarate. MTX also has an inhibitory effect on the activities of the oxidation enzymes of NAD+‐linked substrates without interfering with the oxidation systems of FAD‐linked substrates. The effects… Expand
Methotrexate: Studies on cellular metabolism. III.‐Effect on the transplasma‐membrane redox activity and on ferricyanide‐induced proton extrusion by HeLa cells
It is suggested that inhibition of electron transport and proton extrusion caused by MTX could be associated with other metabolic alterations such as response to the increase in NADH levels and decrease in intracellular pH. Expand
Methotrexate: Studies on cellular metabolism. IV. Effect on the mitochondrial oxidation of cytosolic‐reducing equivalents in HeLa cells
The results obtained are consistent with the view that in HeLa cells, as well as in other tumour cells, the trasport of reducing equivalents from cytoplasmic NADH into the respiratory chain of mitochondria is via the malate‐aspartate shuttle. Expand
Methotrexate: pentose cycle and oxidative stress
The net results appear to show that the biological situation resulting from treatment with MTX leads to a reduction of effectiveness of the antioxidant enzyme defence system. Expand
Effect of methotrexate (MTX) on NAD(P)+ dehydrogenases of HeLa cells: malic enzyme, 2‐oxoglutarate and isocitrate dehydrogenases
An evaluation of the effects of MTX on malic enzyme activity as measured by pyruvate plus lactate production in intact cells supplied with malate showed a decrease of about 40 per cent in metabolite production using 0·4 mM MTX. Expand
Protective effect of lipoic acid against methotrexate-induced oxidative stress in liver mitochondria.
It is suggested that lipoic acid has a potential role in suppressing MTX-induced mitochondrial toxicity, and it affords protection either by reversing the decline of antioxidants or by the directly scavenging the free radicals. Expand
Methotrexate induced mitochondrial injury and cytochrome c release in rat liver hepatocytes
It is suggested that MTX-induced cytotoxicity caused by ROS formation and GSH oxidation leads to oxidative stress and mitochondrial injury in rat hepatocytes. Expand
A study on the possible role of mitochondrial damage reactive nitrogen species and reactive oxygen species in the pathogenesis of methotrexate induced small intestinal damage in the rat
Methotrexate is widely used in the treatment of different malignancies and inflammatory disorders. The therapeutic effect of the drug is through the competitive inhibition of dihydrofolateExpand
Folylpoly-γ-glutamate synthetase: A key determinant of folate homeostasis and antifolate resistance in cancer.
  • S. Raz, M. Stark, Y. Assaraf
  • Biology, Medicine
  • Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy
  • 2016
The current review highlights the crucial role that FPGS plays in maintenance of folate homeostasis under physiological conditions and delineates the plethora of the molecular mechanisms underlying loss of FPGs function and consequent antifolate resistance in cancer. Expand
Activation of glycogenolysis by methotrexate. Influence of calcium and inhibitors of hormone action.
It was concluded that methotrexate acts through a Ca(2+)-dependent mechanism, which is similar to that of the Ca( 2+)- dependent agonists, however, this action seems not to be receptor mediated. Expand
Methotrexate-induced renal oxidative stress in rats: the role of a novel antioxidant caffeic acid phenethyl ester
Investigation of the role of caffeic acid phenethyl ester (Caffeic Ester), a novel antioxidant, on methotrexate-induced renal oxidative stress in rats found that it leads to a reduction in antioxidant enzymatic defense capacity and causes lipid peroxidation in renal tissue. Expand


Methotrexate: Studies on the cellular metabolism. I. Effect on mitochondrial oxygen uptake and oxidative phosphorylation
The effect on the steady‐state of cytochrome b, as well as, the inhibitory effect on state III of respiration with NAD+‐linked substrates, offers a reasonable possibility to suggesting that the inhibition site of MTX could be in a place anterior to cy tochrome b region, and not linked to respiratory chain. Expand
Safranine as a probe of the mitochondrial membrane potential
The membrane potential has been suggested to be the major component of the electrochemical proton gradient under most conditions, and measurements of this potential are therefore essential for the understanding of the mechanism of oxidative phosphorylation and mitochondrial ion transport. Expand
[27] l-Glutamic dehydrogenase from liver:
Publisher Summary This chapter discusses the determination of L-glutamic dehydrogenase from liver. In the course of the assay method, the oxidation of glutamate is measured by the increase of opticalExpand
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