ω-oxidation of 20-hydroxyeicosatetraenoic acid (20-HETE) in cerebral microvascular smooth muscle and endothelium by alcohol dehydrogenase 4

Xixuan H. Collins, Shawn D. Harmon, Terry L. Kaduce, Kristine B. Berst, Xiang Fang, Steven A. Moore, T. Verugopal Raju, John R. Falck, Neal Lee Weintraub, Gregg Duester, Bryce V. Plapp, Arthur A. Spector

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

20-Carboxyeicosatetraenoic acid (20-COOH-AA) is a bioactive metabolite of 20-hydroxyeicosatetraenoic acid (20-HETE), an eicosanoid that produces vasoconstriction in the cerebral circulation. We found that smooth muscle (MSMC) and endothelial (MEC) cultures obtained from mouse brain microvessels convert [3H] 20-HETE to 20-COOH-AA, indicating that the cerebral vasculature can produce this metabolite. The [3H] 20-COOH-AA accumulated primarily in the culture medium, together with additional radiolabeled metabolites identified as the chain-shortened dicarboxylic acids 18-COOH-18:4, 18-COOH-18:3, and 16-COOH-16:3. N-Heptylformamide, a potent inhibitor of alcohol dehydrogenase (ADH), decreased the conversion of [3H]20-HETE to 20-COOH-AA by the MSMC and MEC and also by isolated mouse brain microvessels. Purified mouse and human ADH4, human ADH3, and horse liver ADH1 efficiently oxidized 20-HETE, and ADH4 and ADH3 were detected in MSMC and MEC by Western blotting. N-Heptylformamide inhibited the oxidation of 20-HETE by mouse and human ADH4 but not by ADH3. These results demonstrated that cerebral microvessels convert 20-HETE to 20-COOH-AA and that ADH catalyzes the reaction. Although ADH4 and ADH3 are expressed in MSMC and MEC, the inhibition produced by N-heptylformamide suggests that ADH4 is primarily responsible for 20-COOH-AA formation in the cerebral microvasculature.

Original languageEnglish (US)
Pages (from-to)33157-33164
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number39
DOIs
StatePublished - Sep 30 2005

Fingerprint

Endothelium
Smooth Muscle
Muscle
Microvessels
Oxidation
Metabolites
Alcohol Dehydrogenase
acetaldehyde dehydrogenase (acylating)
Brain
Cerebrovascular Circulation
Dicarboxylic Acids
Eicosanoids
Vasoconstriction
Liver
Horses
Culture Media
20-hydroxy-5,8,11,14-eicosatetraenoic acid
alcohol dehydrogenase IV
Western Blotting
Acids

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

ω-oxidation of 20-hydroxyeicosatetraenoic acid (20-HETE) in cerebral microvascular smooth muscle and endothelium by alcohol dehydrogenase 4. / Collins, Xixuan H.; Harmon, Shawn D.; Kaduce, Terry L.; Berst, Kristine B.; Fang, Xiang; Moore, Steven A.; Raju, T. Verugopal; Falck, John R.; Weintraub, Neal Lee; Duester, Gregg; Plapp, Bryce V.; Spector, Arthur A.

In: Journal of Biological Chemistry, Vol. 280, No. 39, 30.09.2005, p. 33157-33164.

Research output: Contribution to journalArticle

Collins, XH, Harmon, SD, Kaduce, TL, Berst, KB, Fang, X, Moore, SA, Raju, TV, Falck, JR, Weintraub, NL, Duester, G, Plapp, BV & Spector, AA 2005, 'ω-oxidation of 20-hydroxyeicosatetraenoic acid (20-HETE) in cerebral microvascular smooth muscle and endothelium by alcohol dehydrogenase 4', Journal of Biological Chemistry, vol. 280, no. 39, pp. 33157-33164. https://doi.org/10.1074/jbc.M504055200
Collins, Xixuan H. ; Harmon, Shawn D. ; Kaduce, Terry L. ; Berst, Kristine B. ; Fang, Xiang ; Moore, Steven A. ; Raju, T. Verugopal ; Falck, John R. ; Weintraub, Neal Lee ; Duester, Gregg ; Plapp, Bryce V. ; Spector, Arthur A. / ω-oxidation of 20-hydroxyeicosatetraenoic acid (20-HETE) in cerebral microvascular smooth muscle and endothelium by alcohol dehydrogenase 4. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 39. pp. 33157-33164.
@article{74a02f268d734d3b8d33f03e8152a1eb,
title = "ω-oxidation of 20-hydroxyeicosatetraenoic acid (20-HETE) in cerebral microvascular smooth muscle and endothelium by alcohol dehydrogenase 4",
abstract = "20-Carboxyeicosatetraenoic acid (20-COOH-AA) is a bioactive metabolite of 20-hydroxyeicosatetraenoic acid (20-HETE), an eicosanoid that produces vasoconstriction in the cerebral circulation. We found that smooth muscle (MSMC) and endothelial (MEC) cultures obtained from mouse brain microvessels convert [3H] 20-HETE to 20-COOH-AA, indicating that the cerebral vasculature can produce this metabolite. The [3H] 20-COOH-AA accumulated primarily in the culture medium, together with additional radiolabeled metabolites identified as the chain-shortened dicarboxylic acids 18-COOH-18:4, 18-COOH-18:3, and 16-COOH-16:3. N-Heptylformamide, a potent inhibitor of alcohol dehydrogenase (ADH), decreased the conversion of [3H]20-HETE to 20-COOH-AA by the MSMC and MEC and also by isolated mouse brain microvessels. Purified mouse and human ADH4, human ADH3, and horse liver ADH1 efficiently oxidized 20-HETE, and ADH4 and ADH3 were detected in MSMC and MEC by Western blotting. N-Heptylformamide inhibited the oxidation of 20-HETE by mouse and human ADH4 but not by ADH3. These results demonstrated that cerebral microvessels convert 20-HETE to 20-COOH-AA and that ADH catalyzes the reaction. Although ADH4 and ADH3 are expressed in MSMC and MEC, the inhibition produced by N-heptylformamide suggests that ADH4 is primarily responsible for 20-COOH-AA formation in the cerebral microvasculature.",
author = "Collins, {Xixuan H.} and Harmon, {Shawn D.} and Kaduce, {Terry L.} and Berst, {Kristine B.} and Xiang Fang and Moore, {Steven A.} and Raju, {T. Verugopal} and Falck, {John R.} and Weintraub, {Neal Lee} and Gregg Duester and Plapp, {Bryce V.} and Spector, {Arthur A.}",
year = "2005",
month = "9",
day = "30",
doi = "10.1074/jbc.M504055200",
language = "English (US)",
volume = "280",
pages = "33157--33164",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "39",

}

TY - JOUR

T1 - ω-oxidation of 20-hydroxyeicosatetraenoic acid (20-HETE) in cerebral microvascular smooth muscle and endothelium by alcohol dehydrogenase 4

AU - Collins, Xixuan H.

AU - Harmon, Shawn D.

AU - Kaduce, Terry L.

AU - Berst, Kristine B.

AU - Fang, Xiang

AU - Moore, Steven A.

AU - Raju, T. Verugopal

AU - Falck, John R.

AU - Weintraub, Neal Lee

AU - Duester, Gregg

AU - Plapp, Bryce V.

AU - Spector, Arthur A.

PY - 2005/9/30

Y1 - 2005/9/30

N2 - 20-Carboxyeicosatetraenoic acid (20-COOH-AA) is a bioactive metabolite of 20-hydroxyeicosatetraenoic acid (20-HETE), an eicosanoid that produces vasoconstriction in the cerebral circulation. We found that smooth muscle (MSMC) and endothelial (MEC) cultures obtained from mouse brain microvessels convert [3H] 20-HETE to 20-COOH-AA, indicating that the cerebral vasculature can produce this metabolite. The [3H] 20-COOH-AA accumulated primarily in the culture medium, together with additional radiolabeled metabolites identified as the chain-shortened dicarboxylic acids 18-COOH-18:4, 18-COOH-18:3, and 16-COOH-16:3. N-Heptylformamide, a potent inhibitor of alcohol dehydrogenase (ADH), decreased the conversion of [3H]20-HETE to 20-COOH-AA by the MSMC and MEC and also by isolated mouse brain microvessels. Purified mouse and human ADH4, human ADH3, and horse liver ADH1 efficiently oxidized 20-HETE, and ADH4 and ADH3 were detected in MSMC and MEC by Western blotting. N-Heptylformamide inhibited the oxidation of 20-HETE by mouse and human ADH4 but not by ADH3. These results demonstrated that cerebral microvessels convert 20-HETE to 20-COOH-AA and that ADH catalyzes the reaction. Although ADH4 and ADH3 are expressed in MSMC and MEC, the inhibition produced by N-heptylformamide suggests that ADH4 is primarily responsible for 20-COOH-AA formation in the cerebral microvasculature.

AB - 20-Carboxyeicosatetraenoic acid (20-COOH-AA) is a bioactive metabolite of 20-hydroxyeicosatetraenoic acid (20-HETE), an eicosanoid that produces vasoconstriction in the cerebral circulation. We found that smooth muscle (MSMC) and endothelial (MEC) cultures obtained from mouse brain microvessels convert [3H] 20-HETE to 20-COOH-AA, indicating that the cerebral vasculature can produce this metabolite. The [3H] 20-COOH-AA accumulated primarily in the culture medium, together with additional radiolabeled metabolites identified as the chain-shortened dicarboxylic acids 18-COOH-18:4, 18-COOH-18:3, and 16-COOH-16:3. N-Heptylformamide, a potent inhibitor of alcohol dehydrogenase (ADH), decreased the conversion of [3H]20-HETE to 20-COOH-AA by the MSMC and MEC and also by isolated mouse brain microvessels. Purified mouse and human ADH4, human ADH3, and horse liver ADH1 efficiently oxidized 20-HETE, and ADH4 and ADH3 were detected in MSMC and MEC by Western blotting. N-Heptylformamide inhibited the oxidation of 20-HETE by mouse and human ADH4 but not by ADH3. These results demonstrated that cerebral microvessels convert 20-HETE to 20-COOH-AA and that ADH catalyzes the reaction. Although ADH4 and ADH3 are expressed in MSMC and MEC, the inhibition produced by N-heptylformamide suggests that ADH4 is primarily responsible for 20-COOH-AA formation in the cerebral microvasculature.

UR - http://www.scopus.com/inward/record.url?scp=25844481576&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=25844481576&partnerID=8YFLogxK

U2 - 10.1074/jbc.M504055200

DO - 10.1074/jbc.M504055200

M3 - Article

VL - 280

SP - 33157

EP - 33164

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 39

ER -