Hydrogen peroxide stimulates tyrosine phosphorylation of the insulin receptor and its tyrosine kinase activity in intact cells

Koshio, Osamu; Akanuma, Yasuo; Kasuga, Masato

doi:10.1042/bj2500095

Cited by 108 publications

(52 citation statements)

References 26 publications

(16 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Treatment of IR-transfected Chinese hamster ovary cells with antioxidants such as N-acetyl-cysteine or butylated hydroxyanisole inhibited insulin responsiveness, whereas partial inhibition of glutathione metabolism, which intracellularly induces a mild oxidative stress condition, stimulated IR tyrosine phosphorylation when measured in vitro (21). A similar increase in IR kinase activity was observed following cell treatment with hydrogen peroxide (22)(23)(24)(25). Moreover, it has been found that oxidation of critical cysteine residues in the IR ␤-subunit may also result in an increase in its intrinsic tyrosine kinase activity, whereas low concentrations of dithiothreitol inactivates the IR kinase, supporting the importance of oxidation of critical thiol groups in activation of the insulin signaling pathway (26,27).…”

mentioning

confidence: 83%

R-α-Lipoic Acid Action on Cell Redox Status, the Insulin Receptor, and Glucose Uptake in 3T3-L1 Adipocytes

Moini

Tirosh

Park

et al. 2002

Archives of Biochemistry and Biophysics

View full text Add to dashboard Cite

The insulin signaling pathway has been reported to mediate R-␣-lipoic acid-(R-LA-)-stimulated glucose uptake into 3T3-L1 adipocytes and L6 myotubes. We investigated the role of the thiol antioxidant dihydrolipoic acid (DHLA) and intracellular glutathione (GSH) in R-LA-stimulated glucose transport and explored the hypothesis that R-LA could increase glucose uptake into 3T3-L1 adipocytes in an oxidant-mimetic manner. R-LA pretreatment of 3T3-L1 cells stimulated glucose transport at early time points (30 min-6 h), whereas it inhibited glucose uptake at later time points. Analysis of the oxidized and reduced content of LA in cells and medium showed that >90% of lipoic acid present was in its oxidized form. Furthermore, all oxidized forms of LA (S-, R-, and racemic LA) stimulated glucose uptake, whereas the reduced form, dihydrolipoic acid, was ineffective. Intracellular GSH levels were not changed at the early time points (before 12 h), while longer preincubation (24 -48 h) of cells with R-LA significantly increased intracellular GSH. Pretreatment of adipocytes with R-LA increased intracellular peroxide levels at early time points (30 min-6 h), after which it was decreased (12-48 h). R-LA also increased tyrosine phosphorylation of immunoprecipitated insulin receptors from 3T3-L1 adipocytes. These results indicate that (i) 3T3-L1 adipocytes have a low capacity to reduce R-LA and the oxidized form of lipoic acid is responsible for stimulating glucose uptake, (ii) R-LA modulates glucose uptake by changing the intracellular redox status, and (iii) the insulin receptor is a potential cellular target for R-LA action.

show abstract

mentioning

confidence: 83%

R-α-Lipoic Acid Action on Cell Redox Status, the Insulin Receptor, and Glucose Uptake in 3T3-L1 Adipocytes

Moini

Tirosh

Park

et al. 2002

Archives of Biochemistry and Biophysics

View full text Add to dashboard Cite

show abstract

“…H 2 0 2 has been implicated in signal transduction during insulin action in animal systems [67,81]. Significantly, plasma membrane calcium influx, another recognized component of mammalian cell signal-transduction [122], has been observed as an early event in the bacteria-induced hypersensitive reaction of tobacco suspension cells [4].…”

Section: The Role Of Hydrogen Peroxidementioning

confidence: 99%

The generation of oxygen radicals during host plant responses to infection

Sutherland

1991

Physiological and Molecular Plant Pathology

321

166

View full text Add to dashboard Cite

“…Larsson and Cerutti also reported that stimulation of mouse epidermal JB6 cells with oxidants increased their S6 kinase activity [78]. Phosphorylation of the insulin receptor at Ser/Thr residues increased by treatment of rat adipocytes [79] or rat hepatoma cells [80] with a relatively high concentration of H202. H 2 0 2 also increased Tyr phosphorylation [SO, 811.…”

Section: Activation Of the Serum-response Element In Hzoz-treated Cellsmentioning

confidence: 99%

Transcriptional activation of early‐response genes by hydrogen peroxide in a mouse osteoblastic cell line

Nose

Shibanuma

Kikuchi

et al. 1991

European Journal of Biochemistry

272

101

View full text Add to dashboard Cite

HzOZ, like other oxidants, is known to act as a mitogen at low concentrations in resting Balb/3T3 or mouse epidermal JB6 cells. We described previously that H 2 0 2 induces some early response genes in Balb/3T3 cells. We extended these observations using another cell line, MC3T3 (mouse osteoblastic) cells by examination of transcriptional activity of these genes and by using inhibitors of protein kinases. H2O2 increased the expressions of c-fos, c-jun, egr-1 and JE genes which are known to be early response genes and are induced by mitogenic stimuli in many types of cells. Exogenous addition of H z 0 2 increased the mRNA levels of these genes, the kinetics of increase being similar to those of their inductions by a phorbol ester or serum. Nuclear run-on transcription showed that this induction occurred at the transcriptional level. HzOz at 0.1 -0.2 mM induced maximal expressions of c-fus and c-jun, whereas 0.3 mM H z 0 2 was required for induction of stress-induced heme oxygenase mRNA. The inductions of c-fos and c-jun were inhibited by 50 pM H7, a protein kinase inhibitor that is relatively specific for protein kinase C, but were not affected by H9, relatively specific for CAMP-dependent protein kinase. In cells pretreated with 12-0-tetradecanoylphorbol 13-acetate, however, in which protein kinase was supposed to be downregulated, H2O2 induced c-fos and heme oxygenase as efficiently as in untreated cells. H z 0 2 did not increase the phosphorylation of p80 protein, which is known to be a substrate for protein kinase C. Thus, H z 0 2 seemed to induce c-fos and c-jun by activating protein kinases distinct from protein kinase C. Activity of the chloramphenicol acetyltransferase gene under control of the serum-response element of human c-jos genes was increased by HzOz treatment, whereas that under control of CAMP-response element was not affected. These results indicate that the inductions by H 2 0 2 of c-fos and possibly other early response genes are mediated through activation of the serum-response element in their enhancer.

show abstract

Hydrogen peroxide stimulates tyrosine phosphorylation of the insulin receptor and its tyrosine kinase activity in intact cells

Cited by 108 publications

References 26 publications

R-α-Lipoic Acid Action on Cell Redox Status, the Insulin Receptor, and Glucose Uptake in 3T3-L1 Adipocytes

R-α-Lipoic Acid Action on Cell Redox Status, the Insulin Receptor, and Glucose Uptake in 3T3-L1 Adipocytes

The generation of oxygen radicals during host plant responses to infection

Transcriptional activation of early‐response genes by hydrogen peroxide in a mouse osteoblastic cell line

Contact Info

Product

Resources

About