Estrogen receptor a mediates the nongenomic activation of endothelial nitric oxide synthase by estrogen

Chen, Zhong; Yuhanna, Ivan S.; Galcheva-Gargova, Zoya; Karas, Richard H.; Mendelsohn, Michael E.; Shaul, Philip W.

doi:10.1172/jci5347e1

Cited by 277 publications

(383 citation statements)

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“…For example, JNK and ERK1/2 pathways are necessary for lipopolysaccharide (LPS)-and interferon-␥-stimulated iNOS expression in mouse macrophage cells, possibly via ␣-tumor necrosis factor secretion, whereas p38 inhibited induction [31]. The induction of endothelial NOS (eNOS, NOS-3) by estrogen, fibroblast growth factor or epidermal growth factor in endothelial cells involves the Ras-ERK pathway [38,233]. eNOS is phosphorylated, and thus activated, by the serine/threonine protein kinase AKT, which is recruited to the cell membrane by PI3-kinase as an antiapoptotic mechanism in the response of endothelial cells to shear stress [54].…”

Section: Nitric Oxide and Mapk Signalingmentioning

confidence: 99%

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

Schroeter

Boyd

Spencer

et al. 2002

Neurobiology of Aging

310

178

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Oxidative and nitrosative stress is increasingly associated with the pathology of neurodegeneration and aging. The molecular mechanisms underlying oxidative/nitrosative stress-induced neuronal damage are emerging and appear to involve a mode of death in which mitogen-activated protein kinase (MAPK) signaling pathways are strongly implicated. Thus, attention is turning towards the modulation of intracellular signaling as a therapeutic approach against neurodegeneration. Both endogenous and dietary agents have been suggested as potent modulators of intracellular signal transduction, e.g. nitric oxide and flavonoids, respectively. This review addresses recent findings on the biological effects of flavonoids and nitric oxide in neurodegeneration and aims to elucidate the rationale for their prospective use as modulators of cellular signal transduction. © 2002 Elsevier Science Inc. All rights reserved.Keywords: Apoptosis; Oxidative stress; Neuron; Flavonoids; MAP kinase; JNK; ERK; Epicatechin; Nitric oxide; Mitochondria; Redox status; Polyphenols Abbreviations: AKT, serine/threonine kinase (also known as protein kinase B); AP-1, activator protein-1; Apaf-1, apoptosis protease activating factor-1; ASK1, apoptosis signal-regulating kinase-1; Bad, Bcl-2/BclX Lassociated death promoting protein; Bax, pro-apoptotic protein of the Bcl-2 family; Bcl-2, B-cell lymphoma 2: protein with anti-apoptotic properties; BclX L , long form of Bclx: anti-apoptotic protein of the Bcl-2 family; Caspase, cysteinyl aspartic acid-protease; c-Jun, mammalian equivalent of Jun: part of the AP-1 transcription complex; CREB, cAMP response element binding protein; DIABLO/smac, mitochondria-related pro-apoptotic protein: inhibits XIAP; ERK1/2, extracellular signal-related kinase; Fas, CD95: member of the TNF receptor family; GSHST, glutathione Stransferase; JNK, c-Jun amino-terminal kinase; MAPK, mitogen-activated protein kinase; MAPKK, MAPK kinase; MAPKKK, MAPKK kinase; MEK1/2, ERK1/2-specific MAPKK; MKK4/7, JNK-specific MAPKK; MSK1, mitogen-and stress-activated kinase-1; NF-B, nuclear factor of immunoglobulin k locus in B-cells; ONOO − , peroxynitrite anion; p53, pro-apoptotic tumor suppressor gene product; PI3-kinase, phosphoinositol 3-kinase; Ras, small G-protein; RNS, reactive nitrogen species; ROS, reactive oxygen species; RSK, pp90 ribosomal S6 kinase; SAPK, stressactivated protein kinase; XIAP, X-linked inhibitor of apoptosis: inhibits the activation of caspase-9

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Section: Nitric Oxide and Mapk Signalingmentioning

confidence: 99%

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

Schroeter

Boyd

Spencer

et al. 2002

Neurobiology of Aging

310

178

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“…For example, osteocyte apoptosis and bone loss is prevented by the androgen and estrogen steroid receptors through nontranscriptional activation of protein kinase Src and mitogen-activated protein kinase [65,66]. Vascular nitric oxide production and vasodilation by estrogen depends on nontranscriptional activation of eNOS and are mediated by ERα-dependent activation of the PI3 K/Akt pathway [67,68,69]. Indeed, the vascular protective effects of estrogen are dependent on the nontranscriptional activation of eNOS via PI3 K/Akt [68].…”

Section: Rapid Nontranscriptional Effects Of Grmentioning

confidence: 99%

Nontranscriptional actions of the glucocorticoid receptor

Limbourg

Liao

2003

J Mol Med

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Many cellular responses to corticosteroids involve the transcriptional modulation of target genes by a prototypical nuclear receptor, the glucocorticoid receptor (GR). In the classic model of steroid hormone action GR acts as ligand-dependent transcription factor by either activating or repressing gene expression through direct interactions with DNA or other transcription factors. Recent evidence suggests an important role for nontranscriptional effects of GR in the vascular system. The nontranscriptional actions of GR involve the rapid activation of protein kinases, such as phosphatidylinositol-3 kinase and Akt, leading to the activation of endothelial nitric oxide synthase. This novel pathway of steroid hormone action protects against ischemic injury by augmenting blood flow and decreasing vascular inflammation.

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“…Some investigators have been able to demonstrate (38) increased expression of endothelial nitric oxide synthase in women treated with estrogens. The effects of estrogens on nitric oxide synthesis is believed to be manifested by rapid non-genomic (without changes in gene expression) effects (38,39). Elucidation of this phenomenon has indicated that the non-genomic effects may still be modulated by estrogen receptors and the readers are referred to an excellent review of this topic by Mendelsohn and Karas (39).…”

Section: Estrogen and Vascular Tonementioning

confidence: 99%

Estrogen replacement therapy and cardioprotection: mechanisms and controversies

Subbiah

2002

Braz J Med Biol Res

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Epidemiological and case-controlled studies suggest that estrogen replacement therapy might be beneficial in terms of primary prevention of coronary heart disease (CHD). This beneficial effect of estrogens was initially considered to be due to the reduction of low density lipoproteins (LDL) and to increases in high density lipoproteins (HDL). Recent studies have shown that estrogens protect against oxidative stress and decrease LDL oxidation. Estrogens have direct effects on the arterial tissue and modulate vascular reactivity through nitric oxide and prostaglandin synthesis. While many of the effects of estrogen on vascular tissue are believed to be mediated by estrogen receptors a and ß, there is evidence for immediate non-genomic effects. The role of HDL in interacting with 17ß-estradiol including its esterification and transfer of esterified estrogens to LDL is beginning to be elucidated. Despite the suggested positive effects of estrogens, two recent placebo-controlled clinical trials in women with CHD did not detect any beneficial effects on overall coronary events with estrogen therapy. In fact, there was an increase in CHD events in some women. Mutations in thrombogenic genes (factor V Leiden, prothrombin mutation, etc.) in a subset of women may play a role in this unexpected finding. Thus, the cardioprotective effect of estrogens appears to be more complicated than originally thought and requires more research.

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Estrogen receptor a mediates the nongenomic activation of endothelial nitric oxide synthase by estrogen

Cited by 277 publications

References 0 publications

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

Nontranscriptional actions of the glucocorticoid receptor

Estrogen replacement therapy and cardioprotection: mechanisms and controversies

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