Lipoxygenase activity in heart cells

Breitbart, Eyal; Sofer, Yossi; Shainberg, Asher; Grossman, Shlomo

doi:10.1016/0014-5793(96)01017-4

Cited by 14 publications

(9 citation statements)

References 22 publications

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“…A 12−LO isoform has been cloned from cardiac muscle [13] and 12−HETE, the product of 12/15−LO, has been found to be the main LO metabolite in ventricular cardiomyocytes [14]. Our laboratory previously demonstrated the possible involve− ment of 12−HETE in cardiac glucose transport [15,16].…”

Section: Introductionmentioning

confidence: 99%

Altered GLUT4 Translocation in Skeletal Muscle of 12/15-Lipoxygenase Knockout Mice

Vahsen

Rakowski²,

Ledwig³

et al. 2006

Horm Metab Res

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We have recently shown that 12(S)-hydroxyeicosatetraenoic acid plays a role in the organization of actin microfilaments in rat cardiomyocytes, and that inhibition of 12-lipoxygenase abrogates insulin-stimulated GLUT4 translocation in these cells. In the present study, we used mice that were null for the leukocyte 12/15-lipoxygenase to explore the implications of this enzyme for insulin action under IN VIVO conditions. Insulin induced a profound reduction in blood glucose in both control and knockout mice. However, significantly higher serum insulin levels were observed in these animals. GLUT4 expression in heart and skeletal muscle was unaffected in KO mice. Insulin-regulated serine phosphorylation of Akt and GSK3alpha and GSK3beta was unaltered in heart and skeletal muscle of knockout mice, suggesting unaltered insulin signaling. Fractionation of hind limb muscles showed that insulin had induced a prominent translocation of GLUT4 to skeletal muscle plasma membranes in control mice. However, this response was largely reduced in knockout animals. Our data show that the lack of leukocyte 12/15-lipoxygenase does not lead to the development of an insulin-resistant phenotype. However, perturbation of GLUT4 translocation in skeletal muscle of knockout mice may indicate latent insulin resistance, and supports our hypothesis that eicosanoids are involved in insulin-mediated regulation of muscle glucose transport.

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Section: Introductionmentioning

confidence: 99%

Altered GLUT4 Translocation in Skeletal Muscle of 12/15-Lipoxygenase Knockout Mice

Vahsen

Rakowski²,

Ledwig³

et al. 2006

Horm Metab Res

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“…So far, the biological function and significance of the different LO isoforms have remained unclear 5. 12‐LO was found to be expressed in the heart1 and 12( S )‐HETE represents the main LO metabolite in ventricular cardiomyocytes 6…”

Section: Introductionmentioning

confidence: 99%

“…5 was found to be expressed in the heart 1 and 12(S)-HETE represents the main LO metabolite in ventricular cardiomyocytes. 6 Interestingly, 12(S)-HETE induces the phosphorylation of actin fibers, leading to an increased actin filament content and enhancement of actin polymerization. 7,8 Involvement of PKC in this process has been suggested.…”

Section: Introductionmentioning

confidence: 99%

Eicosanoids and the Regulation of Cardiac Glucose Transport

Dransfeld

Rakatzi

Sasson

et al. 2002

Annals of the New York Academy of Sciences

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Intact actin microfilaments are necessary for insulin‐regulated GLUT4 translocation from intracellular pools to the plasma membrane. Products of the lipoxygenase (LO) pathway were shown to be implicated in the regulation of actin cytoskeleton rearrangement. The aim of this study was to examine the role of these LO products for cardiac insulin signaling and glucose uptake, GLUT4 translocation, and actin‐based cytoskeleton structure. Exposure of cardiomyocytes to esculetin or NDGA, two structurally different LO inhibitors, induced a complete inhibition of insulin‐stimulated glucose uptake, whereas control cells showed a threefold stimulation by insulin. Addition of 12(S)‐HETE rendered the NDGA‐treated cells insulin‐sensitive. Early insulin signaling was not changed in cells exposed to LO inhibitors. Cell surface biotinylation of control cells showed a twofold increase of GLUT4 at the cell surface after insulin stimulation. In contrast, the LO inhibitors induced a complete inhibition of insulin‐stimulated GLUT4 translocation. Labeling of the F‐actin cytoskeleton revealed a prominent disassembly of actin fibers in cells exposed to the LO inhibitors. In conclusion, we show here that products of the LO reaction participate in the organization of the actin network in ventricular cardiomyocytes. Inhibition of LO blocks GLUT4 translocation without affecting insulin signaling events. These data suggest that products of the LO reaction participate in the regulation of glucose transport by contribution to a rearrangement of actin cytoskeletal elements.

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“…Thus it has been reported that 12(S)-HETE induces the phosphorylation of major cytoskeletal proteins, like actin, specifically leading to an increased actin filament content and an enhancement of actin polymerization. Breitbart and co-workers [16] first reported the presence of 12-LO activity in rat ventricular cardiomyocytes, with enzyme activity being detected in both the cytosol and microsomal fractions. Consistent with these findings, our confocal data presented here confirm that immunofluorescence specific for actin and 12-LO could be detected in ventricular cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Increasing numbers of certain mammalian LO isoforms (5-, 12-or 15-LO) have been identified in various tissues [13,14], but, for most of them, the biological function and significance remain unclear [12,14,15]. Sigal and co-workers [13] have cloned and characterized a 12-LO isoform from cardiac muscle, and 12(S)-HETE was found to be the main LO metabolite in ventricular cardiomyocytes [16]. This isoform has also been described in a variety of rat, mouse and human tissues [17].…”

Section: Introductionmentioning

confidence: 99%

Eicosanoids participate in the regulation of cardiac glucose transport by contribution to a rearrangement of actin cytoskeletal elements

Dransfeld

Rakatzi

Sasson

et al. 2001

Biochemical Journal

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Intact actin microfilaments are required for insulin-regulated glucose transporter isoform 4 (GLUT4) translocation to the plasma membrane. Lipoxygenase (LO) metabolites have recently been shown to contribute to the regulation of actin cytoskeleton rearrangement. In the present investigation, ventricular cardiomyocytes were used to study the effects of two structurally different LO inhibitors (esculetin and nordihydroguaiaretic acid) on insulin signalling events, glucose uptake, GLUT4 translocation and the actin network organization. Insulin stimulation increased glucose uptake 3-fold in control cells, whereas LO inhibition completely blocked this effect. This was paralleled by a slight reduction in the insulin-induced tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2. However, inhibition of 12-LO did not affect the association of phosphatidylinositol 3-kinase with IRS-1 and the phosphorylation of Akt\protein kinase B in response to insulin. Addition of 12(S)-

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Lipoxygenase activity in heart cells

Cited by 14 publications

References 22 publications

Altered GLUT4 Translocation in Skeletal Muscle of 12/15-Lipoxygenase Knockout Mice

Altered GLUT4 Translocation in Skeletal Muscle of 12/15-Lipoxygenase Knockout Mice

Eicosanoids and the Regulation of Cardiac Glucose Transport

Eicosanoids participate in the regulation of cardiac glucose transport by contribution to a rearrangement of actin cytoskeletal elements

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