Pivotal role of Cu,Zn-superoxide dismutase in endothelium-dependent hyperpolarization

Matsunaga, Keiko; Shimokawa, Hiroaki; Matoba, Tetsuya; Akaike, Takaaki; Talukder, Milton; Hatanaka, Makoto; Fujiki, Takako; Maeda, Hiroshi; Takahashi, Shosuke; Takeshita, Akira

doi:10.1172/jci200319351

Cited by 141 publications

(85 citation statements)

References 43 publications

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“…Furthermore, there is some evidence to suggest that estrogens as well as enhancing antioxidant status by elevating SOD levels also simultaneously provide a vasodilator. It is thought that endothelial Cu/Zn SOD plays a principal role in the hyperpolarization responses elicited by H 2 O 2 (Morikawa et al 2003, Shimokawa & Matoba 2004) and several studies have identified sex differences in H 2 O 2 responses. For example in Cu/Zn SOD KO mice, myogenic tone is increased in arteries of females compared with male controls (Veerareddy et al 2004).…”

Section: Edhfmentioning

confidence: 99%

Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

Villar¹,

Hobbs²,

Ahluwalia

2008

Journal of Endocrinology

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The vascular endothelium plays a crucial role in the regulation of vascular homeostasis by controlling vascular tone, coagulation, and inflammatory responses. These actions are exerted by endothelial factors including nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). The greater incidence of cardiovascular disease (CVD) in men and postmenopausal women compared with premenopausal women implies a vasoprotective phenotype of females, which may be influenced by sex hormones. These hormones, particularly estrogen, have modulatory effects on the endothelium and circulating cells that have been implicated in vascular inflammation and in the development of CVD. EDHF seems to be the predominant endothelial factor in the resistance vasculature of females and this mediator could afford the beneficial cardiovascular risk profile observed in premenopausal woman. In this review, we discuss sex differences in EDHF biology and how sex hormones can modulate EDHF responses. We also review the implication of sex hormone-dependent regulation of EDHF in inflammatory processes, platelet function, and repair after vascular damage, each of which have a critical role in several aspects of the pathogenesis of CVD.

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Section: Edhfmentioning

confidence: 99%

Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

Villar¹,

Hobbs²,

Ahluwalia

2008

Journal of Endocrinology

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“…EETs activate vascular smooth muscle cell large conductance Ca 2ϩ -activated K ϩ channels leading to hyperpolarization of the resting membrane potential and resulting in vasorelaxation and lowering of blood pressure. Indeed, 11,12-EET has been proposed to be identical to endothelium-derived hyperpolarizing factor (Bauersachs et al, 1997;Bolz et al, 2000;Matoba et al, 2000Matoba et al, , 2002Hamilton et al, 2001;Lacza et al, 2002;Miura et al, 2003;Morikawa et al, 2003;Tanaka et al, 2003;Yada et al, 2003). Exogenous application of EETs inhibits vascular smooth muscle cell migration, platelet aggregation, nuclear factor-B activation, and vascular cell adhesion molecule-1 expression (Node et al, 1999;Fleming et al, 2001;Sun et al, 2002;Krotz et al, 2004), suggesting an overall beneficial role for EETs within the vasculature and a protective role in the development of atherosclerosis.…”

mentioning

confidence: 99%

Arachidonic Acid Epoxygenase Metabolites Stimulate Endothelial Cell Growth and Angiogenesis via Mitogen-Activated Protein Kinase and Phosphatidylinositol 3-Kinase/Akt Signaling Pathways

Wang

Wei

Xiao

et al. 2005

J Pharmacol Exp Ther

180

134

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Cytochrome P450 arachidonic acid (AA) epoxygenase metabolites, the epoxyeicosatrienoic acids (EETs), dilate arteries via hyperpolarization of smooth muscle cells and also have nonvasodilatory effects within the vasculature. The present study investigated the angiogenic effects of endogenous and exogenous EETs and the relevant signaling mechanisms involved. Bovine aortic endothelial cells (BAECs) were incubated with synthetic EETs or infected with recombinant adeno-associated viruses (rAAVs) containing CYP2C11-NADPH-cytochrome P450 oxidoreductase (CYPOR), CYP2J2, or CYP102 F87V mutant to increase endogenous levels of EETs. The following endpoints were measured: BAEC proliferation, migration, capillary formation, and in vivo angiogenesis. The potential involvement of various signaling pathways was explored using selective inhibitors. The results showed that transfection with either rAAV-CYP2C11-CYPOR, rAAV-CYP2J2, or rAAV-CYP102 F87V, or incubation with EETs promoted BAEC proliferation, increased migration of BAECs as assessed by Transwell analysis and wound healing assays, and enhanced capillary tubule formation as determined by chicken embryo chorioallantoic membrane assays and tube formation tests on matrigel. The effects of EETs on proliferation, migration, and capillary tubule formation were attenuated by inhibitors of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 (PI3)-kinase/ Akt pathways and partially attenuated by an endothelial nitricoxide synthase (eNOS) inhibitor but not by a protein kinase C inhibitor. In a rat ischemic hind limb model, rAAV-mediated AA epoxygenase transfection induced angiogenesis. We conclude that AA epoxygenase metabolites can promote angiogenesis, which may provide protection to ischemic tissues. The results also suggest that the angiogenic effects of EETs involve the MAPK and PI3-kinase/Akt signaling pathways, and to some extent, the eNOS pathway.Arachidonic acid (AA) is esterified to cell membrane glycerophospholipids and liberated by phospholipase A 2 in response to various stimuli. AA can be activated by three different enzyme pathways: the cyclooxygenase, the lipoxygenase, and the cytochrome P450 (P450) monooxygenase

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“…Consistent with this scenario, altered levels of intracellular calcium (Ca 2+ ) are reported to contribute to the motor neuron degeneration and mitochondrial dysfunction associated with ALS (9-12). Morikawa et al (13) showed that SOD1 beside dismutation had some other functions (13). WT SOD1 could provoke endothelium-dependent relaxation, implying a role of extracellular SOD in smooth muscle function.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Human Wild-Type and Fals Mutant L144P SOD1 on Non-Vascular Smooth Muscle Contractions / EFEKTI HUMANE NORMALNE I FALS MUTIRANE L144P SOD1 NA NEVASKULARNE KONTRAKCIJE GLATKIH MIŠIĆA

Nikolić‐Kokić¹,

Oreščanin-Dušić²,

Slavić³

et al. 2013

Journal of Medical Biochemistry

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SummaryBackground: Mutated copper, zinc-containing superoxide dismutase (SOD1) may self-aggregate, an event that could also be an initial cause of motor neuron malfunction leading to disease onset. The effects of human mutated SOD1 protein from the blood of familial amyotrophic lateral sclerosis (FALS) patients bearing Leu144Phe (L144F) mutation were compared to wild-type (WT) human SOD1 derived from healthy examinees, for enzymatic activity and the effects on isometric contractions of non-vascular smooth muscle. Methods: We isolated WT and L144F SOD1 enzymes from eight patients with FALS, L144F mutation in exon 5 and eight healthy controls. We then investigated SOD1 activities in the obtained samples by the adrenaline method and profiled them electrophoretically. Finally, we applied WT and L144F SOD1 on the isolated rat uterus. Results: L144F SOD1 showed lower superoxide-dismutating activity compared to WT human SOD1. We found that, in contrast to WT human SOD1, mutated L144F does not induce smooth muscle relaxation. Conclusions: Our data suggest that the lack of relaxation of muscle tonus in the presence of mutated SOD1 may have pathogenic feedback effects in FALS.

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Pivotal role of Cu,Zn-superoxide dismutase in endothelium-dependent hyperpolarization

Cited by 141 publications

References 43 publications

Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

Arachidonic Acid Epoxygenase Metabolites Stimulate Endothelial Cell Growth and Angiogenesis via Mitogen-Activated Protein Kinase and Phosphatidylinositol 3-Kinase/Akt Signaling Pathways

The Effects of Human Wild-Type and Fals Mutant L144P SOD1 on Non-Vascular Smooth Muscle Contractions / EFEKTI HUMANE NORMALNE I FALS MUTIRANE L144P SOD1 NA NEVASKULARNE KONTRAKCIJE GLATKIH MIŠIĆA

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