ანოტაცია
ხსნადი ეპოქსიდ ჰიდროლაზა (ეჰ) ბიფუნქციური ჰომოდიმერული ფერმენტი იდენტიფიცირებულია როგორც მცენარეებში, ასევე ძუძუმწოვრებში. იგი ხელს უწყობს ეპოქსიეიკოზატრიენოის (ეეტ) მჟავების კონვერსიას ბიოლოგიურად ნაკლებად აქტიურ დიჰიდროქსიეიკოზატრიენოის მჟავებად (დჰეტ). ხსნადი ეჰ მონაწილეობს არაქიდონის, ლინოლეის და სხვა ცხიმოვანი მჟავების ეპოქსიდების მეტაბოლიზმში ისევე, როგორც ენდოგენური ქიმიური მედიატორების ლიბერაციის პროცესში. ბოლო წლების ლიტერატურული მონაცემების თანახმად, ხსნადი ეჰ ინჰიბიტორები ეეტ-ს დონის მომატებით ისევე, როგორც თვით ეეტ ხელს უწყობენ პოზიტიური ცვლილებების განვითარებას არტერიული ჰიპერტენზიის, დიაბეტის, ათეროსკლეროზის და ანთებითი დაავადებების მიმდინარეობის პროცესში.
წყაროები
1. Ai D., Pang W., Li N., Xu M. et al. Soluble epoxide hydrolase plays essential role in angiotensin II-induced cardiac hypertrophy. Proc. Nat. Acad. Sci. USA, 2009, 106:564-569.
2. Davis B.B., Thompson D. A., Howard L. L.Morisseau C., Hammock B. D. Inhibitors of soluble epoxide hydrolase attenuate vascular smooth muscle cell proliferation. www.pnas.org/cg;/do;/10.10.73.phas.261710799
3. Dimitripolou C., West L., Field M. B., White R. E., Reddy L. M., Falck R., Imig D. Protein phosphatase 2A and Ca 2+ -activated K channels contribute to 11,12-epoxyeicosatrienoic acid analog mediated mesenteric arterial relaxation. J. Prostaglandins and other lipid mediators. 2007, 83:50-61.
4. Dorrance A. M., Rupp N., Pollock D. M., Newman J. N., Hamock B. D., Imig D. An epoxide hydrolase inhibitor, 12-(3-adamantan-1yl-ureido) dodecanoic acid (AUDA) reduces ischemic cerebral infarct size in stroke-prone spontaneously hypertensive rats. J. Cardiovasc. Pharmacol. 2005, 46:842-848.
5. Fleming I. Cytochrome P450 and vascular homeostasis. J. Circ. Res. 2001, 89:753-762.
6. Fornage M., Hinojos C. A., Nurowska B. W. et al. Polymorphism in soluble epoxide hydrolase and blood pressure in spontaneously hypertensive rats. J. Hypertension. 2002, 40:485-490.
7. Honetschlagerova Z., Vanourkova Z., Sporkova A., Kramer H. J. et al. Renal mechanisms contributing to the antihypertensive action of soluble epoxide hydrolase inhibition in Ren-2-transgenic rats with inducible hypertension. J. Physiol. 2010, 589:207-219.
8. Imig D. Targeting epoxides for organ damage in hypertension. J. Cardiovasc. pharmacol 2010. 56:329-335.
9. Imig D., Hammock B. D. Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases. J. Nat. Rev. Drug. Discov. 2009, 8:794-805.
10. Imig J. D. Epoxides and soluble epoxide hydrolase in cardiovascular physiology. J. Physiol. Rev. 2012, 92: 101-130.
11. Imig D., Simpkins A. N., Renic M., Harder D. K. Cytochrome p-450 eicosanoids and cerebral vascular function. Expert Rev. Mol. Med. 2011. 13:17.
12. Imig D., Zhac X., Zaharis C. Z., Olearczyk J. I., Pollock D. M. et al. An orally active epoxide hydrolase inhibitor lowers blood pressure and provides renal protection in salt sensitive hypertension. J. Hypertension. 2011. 19: 983-992.
13. Koerner I. P., Jacks R., Debarber A. E., Koop D., Mao P., Grant D. F., Alkayed N. J. Polymorphisms in the human soluble epoxide hydrolase gene EPHX2 linked to neuronal survival after ischemic injury. J. Neurosci 207, 27:4642-4649.
14. Larsen B. T., Miura H., Hatoum O. A., Campbell W. B., Hammock B. D., et al. Epoxyeicosatrienoic and dihydroxyicosatrienoic acids dilate human coronary arterioles via BK (Ca) channels implications for soluble epoxide hydrolase inhibition. Am. J. Physiol. Heart circ. Physiol. 2006, 290:H491-H499.
15. Li J., Caroll M. A., Chander P. N., Falck R., Sangras B., Sier C. T. Soluble epoxide hydrolase inhibitor, AUDA, prevents early salt-sensitive hypertension. Front. Biosci 2008, 13:3480-3487
16. Marino P. J. Soluble epoxide hydrolase, a target with multiple opportunities for cardiovascular drug discovery. Curr. Top. Med. Chem. 2009, 9:452-463.
17. Merkel M. J., Liu L., Cao Z., Packwood W., Young J. et al. Inhibition of soluble epoxide hydrolase preserves cardiomyocytes role of STAT3 Signaling. Am. J. Physiol. Heart Circ. Physiol. 2010, 298:H679-687.
18. Michaelis U. R., Fleiming J. From endothelium-derived hyperpolarizing factor (EDHF) and cell signaling pharmacol. Ther 2006, 111:584-595.
19. Morisseau C., Hammock B. D. Epoxide hydrolases mechanisms, inhibitor designs, and biological roles Annu. Rev. Pharmacol, Toxicol. 2005, 45:311-333.
20. Node K., Huo Y., Ruan X., Yang B. et al. Anti-inflammatory properties of cytochrome p-450 epoxygenasederived eicosanoids. J. Science 1999; 235:1276-1279.
21. Roman R. J. p-450 metabolites of arachidonic acid in the control of cardiovascular function. J. Physiol. Rev. 2002;82:131-185.
22. Simpkins A. N., Rudic R. D., Schreihofer D. S., Roy S., Manhiani M. et al. Soluble epoxide inhibition is protective against cerebral ischemia via vascular and neural protection. Am. J. Pathol. 2009. 174:2086-2095.
23. Schmelzer K. R., Kubala L., Newman J. A. et al. Soluble epoxide hydrolase is a therapeutic target for acute inflammation. Proc. Nat. Acad. Sci. USA. 2005, 102:9772-9777.
24. Spector A. A., Fang X., Snyder G. D., Weintraub N. L. Epoxyeicosatrienoic acids (EETs) metabolism and biochemical function. J. Prog. Lipid Res. 2004, 43:55-90.
25. Yang S., Lin L., Chen J. K., Lee C. R., Seubert S. M. et al. Cytochrome p-450 epoxygenases protect endothelial cells from apoptosis induced by tumor necrosis factor alpha via MAPK and PI3K/Akt signaling pathways. Am. J. physiol. Heart Circ. Physiol. 2007, 293:H142-H151
2. Davis B.B., Thompson D. A., Howard L. L.Morisseau C., Hammock B. D. Inhibitors of soluble epoxide hydrolase attenuate vascular smooth muscle cell proliferation. www.pnas.org/cg;/do;/10.10.73.phas.261710799
3. Dimitripolou C., West L., Field M. B., White R. E., Reddy L. M., Falck R., Imig D. Protein phosphatase 2A and Ca 2+ -activated K channels contribute to 11,12-epoxyeicosatrienoic acid analog mediated mesenteric arterial relaxation. J. Prostaglandins and other lipid mediators. 2007, 83:50-61.
4. Dorrance A. M., Rupp N., Pollock D. M., Newman J. N., Hamock B. D., Imig D. An epoxide hydrolase inhibitor, 12-(3-adamantan-1yl-ureido) dodecanoic acid (AUDA) reduces ischemic cerebral infarct size in stroke-prone spontaneously hypertensive rats. J. Cardiovasc. Pharmacol. 2005, 46:842-848.
5. Fleming I. Cytochrome P450 and vascular homeostasis. J. Circ. Res. 2001, 89:753-762.
6. Fornage M., Hinojos C. A., Nurowska B. W. et al. Polymorphism in soluble epoxide hydrolase and blood pressure in spontaneously hypertensive rats. J. Hypertension. 2002, 40:485-490.
7. Honetschlagerova Z., Vanourkova Z., Sporkova A., Kramer H. J. et al. Renal mechanisms contributing to the antihypertensive action of soluble epoxide hydrolase inhibition in Ren-2-transgenic rats with inducible hypertension. J. Physiol. 2010, 589:207-219.
8. Imig D. Targeting epoxides for organ damage in hypertension. J. Cardiovasc. pharmacol 2010. 56:329-335.
9. Imig D., Hammock B. D. Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases. J. Nat. Rev. Drug. Discov. 2009, 8:794-805.
10. Imig J. D. Epoxides and soluble epoxide hydrolase in cardiovascular physiology. J. Physiol. Rev. 2012, 92: 101-130.
11. Imig D., Simpkins A. N., Renic M., Harder D. K. Cytochrome p-450 eicosanoids and cerebral vascular function. Expert Rev. Mol. Med. 2011. 13:17.
12. Imig D., Zhac X., Zaharis C. Z., Olearczyk J. I., Pollock D. M. et al. An orally active epoxide hydrolase inhibitor lowers blood pressure and provides renal protection in salt sensitive hypertension. J. Hypertension. 2011. 19: 983-992.
13. Koerner I. P., Jacks R., Debarber A. E., Koop D., Mao P., Grant D. F., Alkayed N. J. Polymorphisms in the human soluble epoxide hydrolase gene EPHX2 linked to neuronal survival after ischemic injury. J. Neurosci 207, 27:4642-4649.
14. Larsen B. T., Miura H., Hatoum O. A., Campbell W. B., Hammock B. D., et al. Epoxyeicosatrienoic and dihydroxyicosatrienoic acids dilate human coronary arterioles via BK (Ca) channels implications for soluble epoxide hydrolase inhibition. Am. J. Physiol. Heart circ. Physiol. 2006, 290:H491-H499.
15. Li J., Caroll M. A., Chander P. N., Falck R., Sangras B., Sier C. T. Soluble epoxide hydrolase inhibitor, AUDA, prevents early salt-sensitive hypertension. Front. Biosci 2008, 13:3480-3487
16. Marino P. J. Soluble epoxide hydrolase, a target with multiple opportunities for cardiovascular drug discovery. Curr. Top. Med. Chem. 2009, 9:452-463.
17. Merkel M. J., Liu L., Cao Z., Packwood W., Young J. et al. Inhibition of soluble epoxide hydrolase preserves cardiomyocytes role of STAT3 Signaling. Am. J. Physiol. Heart Circ. Physiol. 2010, 298:H679-687.
18. Michaelis U. R., Fleiming J. From endothelium-derived hyperpolarizing factor (EDHF) and cell signaling pharmacol. Ther 2006, 111:584-595.
19. Morisseau C., Hammock B. D. Epoxide hydrolases mechanisms, inhibitor designs, and biological roles Annu. Rev. Pharmacol, Toxicol. 2005, 45:311-333.
20. Node K., Huo Y., Ruan X., Yang B. et al. Anti-inflammatory properties of cytochrome p-450 epoxygenasederived eicosanoids. J. Science 1999; 235:1276-1279.
21. Roman R. J. p-450 metabolites of arachidonic acid in the control of cardiovascular function. J. Physiol. Rev. 2002;82:131-185.
22. Simpkins A. N., Rudic R. D., Schreihofer D. S., Roy S., Manhiani M. et al. Soluble epoxide inhibition is protective against cerebral ischemia via vascular and neural protection. Am. J. Pathol. 2009. 174:2086-2095.
23. Schmelzer K. R., Kubala L., Newman J. A. et al. Soluble epoxide hydrolase is a therapeutic target for acute inflammation. Proc. Nat. Acad. Sci. USA. 2005, 102:9772-9777.
24. Spector A. A., Fang X., Snyder G. D., Weintraub N. L. Epoxyeicosatrienoic acids (EETs) metabolism and biochemical function. J. Prog. Lipid Res. 2004, 43:55-90.
25. Yang S., Lin L., Chen J. K., Lee C. R., Seubert S. M. et al. Cytochrome p-450 epoxygenases protect endothelial cells from apoptosis induced by tumor necrosis factor alpha via MAPK and PI3K/Akt signaling pathways. Am. J. physiol. Heart Circ. Physiol. 2007, 293:H142-H151
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