ROS-dependent Syk and Pyk2-mediated STAT1 activation is required for 15(S)-hydroxyeicosatetraenoic acid-induced CD36 expression and foam cell formation

Sivareddy Kotla, Nikhlesh Singh, James G. Traylor, A. Wayne Orr, Rao Gadiparthi

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

15(S)-Hydroxyeicosatetraenoic acid (15(S)-HETE), the major 15-lipoxygenase 1/2 (15-LO1/2) metabolite of arachidonic acid (AA), induces CD36 expression through xanthine oxidase and NADPH oxidase-dependent ROS production and Syk and Pyk2-dependent STAT1 activation. In line with these observations, 15(S)-HETE also induced foam cell formation involving ROS, Syk, Pyk2, and STAT1-mediated CD36 expression. In addition, peritoneal macrophages from Western diet-fed ApoE-/-mice exhibited elevated levels of xanthine oxidase and NADPH oxidase activities, ROS production, Syk, Pyk2, and STAT1 phosphorylation, and CD36 expression compared to those from ApoE-/-:12/15-LO-/-mice and these events correlated with increased lipid deposits, macrophage content, and lesion progression in the aortic roots. Human atherosclerotic arteries also showed increased 15-LO1 expression, STAT1 phosphorylation, and CD36 levels as compared to normal arteries. Together, these findings suggest that 12/15-LO metabolites of AA, particularly 12/15(S)-HETE, might play a crucial role in atherogenesis by enhancing foam cell formation.

Original languageEnglish (US)
Pages (from-to)147-162
Number of pages16
JournalFree Radical Biology and Medicine
Volume76
DOIs
StatePublished - Jan 1 2014

Fingerprint

Hydroxyeicosatetraenoic Acids
Foam Cells
Lipoxygenase
Xanthine Oxidase
NADPH Oxidase
Apolipoproteins E
Arachidonic Acid
Foams
Phosphorylation
Arteries
Macrophages
Chemical activation
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Arachidonate 15-Lipoxygenase
Metabolites
Peritoneal Macrophages
Atherosclerosis
Nutrition
Lipids
Deposits

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

Cite this

@article{2ae7e96dbbb748999a7424f29a4fbba4,
title = "ROS-dependent Syk and Pyk2-mediated STAT1 activation is required for 15(S)-hydroxyeicosatetraenoic acid-induced CD36 expression and foam cell formation",
abstract = "15(S)-Hydroxyeicosatetraenoic acid (15(S)-HETE), the major 15-lipoxygenase 1/2 (15-LO1/2) metabolite of arachidonic acid (AA), induces CD36 expression through xanthine oxidase and NADPH oxidase-dependent ROS production and Syk and Pyk2-dependent STAT1 activation. In line with these observations, 15(S)-HETE also induced foam cell formation involving ROS, Syk, Pyk2, and STAT1-mediated CD36 expression. In addition, peritoneal macrophages from Western diet-fed ApoE-/-mice exhibited elevated levels of xanthine oxidase and NADPH oxidase activities, ROS production, Syk, Pyk2, and STAT1 phosphorylation, and CD36 expression compared to those from ApoE-/-:12/15-LO-/-mice and these events correlated with increased lipid deposits, macrophage content, and lesion progression in the aortic roots. Human atherosclerotic arteries also showed increased 15-LO1 expression, STAT1 phosphorylation, and CD36 levels as compared to normal arteries. Together, these findings suggest that 12/15-LO metabolites of AA, particularly 12/15(S)-HETE, might play a crucial role in atherogenesis by enhancing foam cell formation.",
author = "Sivareddy Kotla and Nikhlesh Singh and Traylor, {James G.} and {Wayne Orr}, A. and Rao Gadiparthi",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/j.freeradbiomed.2014.08.007",
language = "English (US)",
volume = "76",
pages = "147--162",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - ROS-dependent Syk and Pyk2-mediated STAT1 activation is required for 15(S)-hydroxyeicosatetraenoic acid-induced CD36 expression and foam cell formation

AU - Kotla, Sivareddy

AU - Singh, Nikhlesh

AU - Traylor, James G.

AU - Wayne Orr, A.

AU - Gadiparthi, Rao

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 15(S)-Hydroxyeicosatetraenoic acid (15(S)-HETE), the major 15-lipoxygenase 1/2 (15-LO1/2) metabolite of arachidonic acid (AA), induces CD36 expression through xanthine oxidase and NADPH oxidase-dependent ROS production and Syk and Pyk2-dependent STAT1 activation. In line with these observations, 15(S)-HETE also induced foam cell formation involving ROS, Syk, Pyk2, and STAT1-mediated CD36 expression. In addition, peritoneal macrophages from Western diet-fed ApoE-/-mice exhibited elevated levels of xanthine oxidase and NADPH oxidase activities, ROS production, Syk, Pyk2, and STAT1 phosphorylation, and CD36 expression compared to those from ApoE-/-:12/15-LO-/-mice and these events correlated with increased lipid deposits, macrophage content, and lesion progression in the aortic roots. Human atherosclerotic arteries also showed increased 15-LO1 expression, STAT1 phosphorylation, and CD36 levels as compared to normal arteries. Together, these findings suggest that 12/15-LO metabolites of AA, particularly 12/15(S)-HETE, might play a crucial role in atherogenesis by enhancing foam cell formation.

AB - 15(S)-Hydroxyeicosatetraenoic acid (15(S)-HETE), the major 15-lipoxygenase 1/2 (15-LO1/2) metabolite of arachidonic acid (AA), induces CD36 expression through xanthine oxidase and NADPH oxidase-dependent ROS production and Syk and Pyk2-dependent STAT1 activation. In line with these observations, 15(S)-HETE also induced foam cell formation involving ROS, Syk, Pyk2, and STAT1-mediated CD36 expression. In addition, peritoneal macrophages from Western diet-fed ApoE-/-mice exhibited elevated levels of xanthine oxidase and NADPH oxidase activities, ROS production, Syk, Pyk2, and STAT1 phosphorylation, and CD36 expression compared to those from ApoE-/-:12/15-LO-/-mice and these events correlated with increased lipid deposits, macrophage content, and lesion progression in the aortic roots. Human atherosclerotic arteries also showed increased 15-LO1 expression, STAT1 phosphorylation, and CD36 levels as compared to normal arteries. Together, these findings suggest that 12/15-LO metabolites of AA, particularly 12/15(S)-HETE, might play a crucial role in atherogenesis by enhancing foam cell formation.

UR - http://www.scopus.com/inward/record.url?scp=84907224934&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907224934&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2014.08.007

DO - 10.1016/j.freeradbiomed.2014.08.007

M3 - Article

VL - 76

SP - 147

EP - 162

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

ER -