Angiotoxicity of Oxygenated Sterols and Possible Precursors

Imai, Hisashi; Werthessen, Nicholas T.; Subramanyam, V.; Lequesne, P. W.; Soloway, Albert H.; Kanisawa, Masayoshi

doi:10.1126/science.7352277

Cited by 194 publications

(57 citation statements)

References 18 publications

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“…An additional function of sEH is postulated to be the formation and/or degradation of endogenous chemical mediators, (e.g. mediators of the arachidonate cascade; Carroll, 1987;Imai et aL, 1980, Sugiyama et aL, 1987.…”

Section: Introductionmentioning

confidence: 99%

Characterization of an Arabidopsis cDNA for a soluble epoxide hydrolase gene that is inducible by auxin and water stress

et al. 1994

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SummaryA cDNA (1122 bp) was isolated from a cDNA library prepared from Arabidopais thaliana L. that had been subjected to drought stress for I h. The sequencing of a genomic clone corresponding to the cDNA and Sl mepplng analysis revealed that the cDNA lacked the first 6 bp from its translational start (ATG). The resulting open reading frame encodes a polypaptlde of 321 amino acids, and the calculated molecular weight of this polypeptide is 36 423 De. The deduced amino acid sequence shows a high degree of similarity to C terminal halves of those of soluble epoxide hydrolases (sEHs) of human, mouse and rat, 35.5%, 34.1% and 33.1%, respectively. The cDNA was expressed In Escherichla coil cells, and the expressed protein migrates at 40 kDa when analyzed by SDS-PAGE. The recombinant protein at 40 kDa Is much smaller than the mammalian sEH (58 kDa) but has characteristics of activity and inhibition slmller to the mammalian sEHs when assayed with the substrate trans-stilbene oxide and the inhibitors 4-fluorochalcone oxide (4FCO), (2R,3R)-3-(4-nitrophenyl) glycidol (RRNPG), and (2S,3S)-3-(4-nitrophenyl)glycidol (SSNPG), which indicates that the cDNA did encode a soluble epoxide hydrolese of A. thallana (AtsEH). Drought stress, but not heat or cold stress, slightly Increased the accu-

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Section: Introductionmentioning

confidence: 99%

Characterization of an Arabidopsis cDNA for a soluble epoxide hydrolase gene that is inducible by auxin and water stress

et al. 1994

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“…Although cholesterol itself has no direct angiotoxicity, it forms cholesterol oxides that have multiple toxic effects on the vasculature. 78 Cholesterol oxides, including 7␤-hydroxycholesterol, 7-ketocholesterol, 19-hydroxycholesterol, cholesterol 5␣,-6␣-epoxide, and 25-hydroxycholesterol all promote the loss of cell adhesion and increase the rate of apoptosis in cultured endothelial cells. 79 Cholesterol oxides promote disruption of actin microfilaments, most notably with the disappearance of stress fibers within the cell body.…”

Section: Apoptosis In Coronary Diseasesmentioning

confidence: 99%

Apoptosis

Best

Hasdai

Sangiorgi

et al. 1999

ATVB

108

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Abstract-Apoptosis is an active form of cell death that is intricately regulated and distinct from necrosis. Data suggest that apoptosis may play a role in the pathophysiology of coronary atherosclerotic disease. Anatomic evidence of apoptosis has been observed in coronary atherosclerosis, restenosis, and transplant arteriopathy, accompanied by an increase in biochemical and genetic markers of apoptosis. Vasoactive substances such as nitric oxide and angiotensin II also regulate vascular smooth muscle cell apoptosis; vasodilating factors may induce apoptosis, whereas vasoconstricting factors may inhibit apoptosis. The aim of this article is to review key points regarding the detection of apoptosis, its regulation, and its possible role in the pathogenesis of coronary artery disease. (Arterioscler Thromb Vasc Biol.

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“…Cholesterol and oxidized lipoproteins have been associated with the genesis of diseases [1], and cholesterol oxides (also termed oxysterols), the oxygenated derivatives of cholesterol, might be causative agents [2][3][4][5][6][7]. An excessive amount of cholesterol oxides damages endothelial cells [8,9], smooth muscle cells [2,10], and fibroblasts [11,12], and accumulating evidence suggests that cholesterol oxides are toxic to neural cells in nerve growth factor-differentiated neuronal PC12 cells as a model for sympathetic neurons [13,14], cultured cerebellar granule cells [1], and microglial cells [15].…”

Section: Introductionmentioning

confidence: 99%

“…An excessive amount of cholesterol oxides damages endothelial cells [8,9], smooth muscle cells [2,10], and fibroblasts [11,12], and accumulating evidence suggests that cholesterol oxides are toxic to neural cells in nerve growth factor-differentiated neuronal PC12 cells as a model for sympathetic neurons [13,14], cultured cerebellar granule cells [1], and microglial cells [15]. Although the molecular mechanisms by which cholesterol…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effects of Ginsenoside Rg₃against 24-OH-cholesterol-induced Cytotoxicity in Cortical Neurons

Roh¹,

Kim²,

Kang³

et al. 2010

Journal of Ginseng Research

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Ginsenoside Rg 3 (Rg 3 ), one of the active ingredients in Panax ginseng, attenuates NMDA receptor-mediated currents in vitro and antagonizes NMDA receptors through a glycine modulatory site in rat cultured hippocampal neurons. In the present study, we examined the neuroprotective effects of Rg 3 on 24-hydroxycholesterol (24-OH-chol)-induced cytotoxicity in vitro. The results showed that Rg 3 treatment significantly and dose-dependently inhibited 24-OH-chol-induced cell death in rat cultured cortical neurons, with an IC 50 value of 28.7 ± 7.5 μm. Furthermore, the Rg 3 treatment not only significantly reduced DNA damage, but also dose-dependently attenuated 24-OH-chol-induced caspase-3 activity. To study the mechanisms underlying the in vitro neuroprotective effects of Rg 3 against 25-OH-chol-induced cytotoxicity, we also examined the effect of Rg 3 on intracellular Ca 2+ elevations in cultured neurons and found that Rg 3 treatment dose-dependently inhibited increases in intracellular Ca 2+, with an IC 50 value of 40.37 ± 12.88 μm. Additionally, Rg 3 treatment dose-dependently inhibited apoptosis with an IC 50 of 47.3 ± 14.2 μm. Finally, after confirming the protective effect of Rg 3 using a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, we found that Rg 3 is an active component in ginseng-mediated neuroprotection. These results collectively indicate that Rg 3 -induced neuroprotection against 24-OH-chol in rat cortical neurons might be achieved via inhibition of a 24-OH-chol-mediated Ca 2+ channel. This is the first report to employ cortical neurons to study the neuroprotective effects of Rg 3 against 24-OH-chol. In conclusion, Rg 3 was effective for protecting cells against 24-OH-chol-induced cytotoxicity in rat cortical neurons. This protective ability makes Rg 3 a promising agent in pathologies implicating neurodegeneration such as apoptosis or neuronal cell death.

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Angiotoxicity of Oxygenated Sterols and Possible Precursors

Cited by 194 publications

References 18 publications

Characterization of an Arabidopsis cDNA for a soluble epoxide hydrolase gene that is inducible by auxin and water stress

Characterization of an Arabidopsis cDNA for a soluble epoxide hydrolase gene that is inducible by auxin and water stress

Apoptosis

Neuroprotective Effects of Ginsenoside Rg₃against 24-OH-cholesterol-induced Cytotoxicity in Cortical Neurons

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Angiotoxicity of Oxygenated Sterols and Possible Precursors

Cited by 194 publications

References 18 publications

Characterization of an Arabidopsis cDNA for a soluble epoxide hydrolase gene that is inducible by auxin and water stress

Characterization of an Arabidopsis cDNA for a soluble epoxide hydrolase gene that is inducible by auxin and water stress

Apoptosis

Neuroprotective Effects of Ginsenoside Rg3against 24-OH-cholesterol-induced Cytotoxicity in Cortical Neurons

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Product

Resources

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Neuroprotective Effects of Ginsenoside Rg₃against 24-OH-cholesterol-induced Cytotoxicity in Cortical Neurons