12/15-Lipoxygenase signaling in the endoplasmic reticulum stress response

Angiotensin II activates cPLA2α and releases arachidonic acid from tissue phospholipids which mediate or modulate one or more cardiovascular effects of angiotensin II and has been implicated in hypertension. Since arachidonic acid release is the rate limiting step in eicosanoid production, cPLA2α might play a central role in the development of angiotensin II-induced hypertension. To test this hypothesis, we investigated the effect of angiotensin II infusion for 13 days by micro-osmotic pumps on systolic blood pressure and associated pathogenesis in wild type (cPLA2α+/+) and cPLA2α−/− mice. Angiotensin II-induced increase in systolic blood pressure in cPLA2α+/+ mice was abolished in cPLA2α−/− mice; increased systolic blood pressure was also abolished by the arachidonic acid metabolism inhibitor, 5,8,11,14-eicosatetraynoic acid in cPLA2α+/+ mice. Angiotensin II in cPLA2α+/+ mice increased cardiac cPLA2 activity and urinary eicosanoid excretion, decreased cardiac output, caused cardiovascular remodeling with endothelial dysfunction and increased vascular reactivity in cPLA2α+/+ mice; these changes were diminished in cPLA2α−/− mice. Angiotensin II also increased cardiac infiltration of F4/80+ macrophages and CD3+ T lymphocytes, cardiovascular oxidative stress, expression of endoplasmic reticulum stress markers p58IPK and CHOP in cPLA2α+/+ but not cPLA2α−/− mice. Angiotensin II increased cardiac activity of ERK1/2 and cSrc in cPLA2α+/+ but not cPLA2α−/− mice. These data suggest that angiotensin II-induced hypertension and associated cardiovascular pathophysiological changes are mediated by cPLA2α activation, most likely through the release of arachidonic acid and generation of eicosanoids with predominant pro-hypertensive effects and activation of one or more signaling molecules including ERK1/2 and cSrc.

show abstract

“…In support of this view, 12/15-LO has been implicated in ER stress in adipocytes, pancreatic islets, and rat liver. 65 …”

Section: Discussionmentioning

confidence: 99%

Cytosolic Phospholipase A ₂ α Is Critical for Angiotensin II–Induced Hypertension and Associated Cardiovascular Pathophysiology

et al. 2015

View full text Add to dashboard Cite

show abstract

“…inflammation and insulin resistance [7]. Under ER stress conditions, mammalian cells initiate an adaptive response known as the unfolded protein response (UPR) via three upstream signaling proteins; PKR-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6) [8].…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Palmitate increases musclin gene expression through activation of PERK signaling pathway in C2C12 myotubes

Guo

Mao

et al. 2015

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

“…Obesity resulting from expansion of adipose tissue is associated with low-grade inflammation, and lipoxygenase enzymes have been linked to inflammatory changes leading to the development of obesity (Ye 2009;Cole et al 2012;Dobrian et al 2010). Adipocytes express ; studies indicate overexpression of 15-LOX gene in adipocytes isolated from obese rats when compared with lean rats (Sears et al 2009;Chanez et al 2002).…”

Section: Introductionmentioning

confidence: 99%

15(S)-HETE-induced angiogenesis in adipose tissue is mediated through activation of PI3K/Akt/mTOR signaling pathway

Soumya

Binu

Helen

et al. 2013

Biochem. Cell Biol.

View full text Add to dashboard Cite

Chronic low-grade inflammation underlies obesity and associated metabolic dysfunctions. Lipoxygenase pathways are activated in adipose tissue during obese conditions. Since adipogenesis is associated with angiogenesis, the present study was designed to examine the role of 15-lipoxygenase metabolite, 15(S)-hydroxyeicosatetraenoic acid [15(S)-HETE] on angiogenesis in adipose tissue. Results showed that 15(S)-HETE induced sprouting in fat pad stromovascular tissues, induced morphological changes relevant to angiogenesis in endothelial cells derived from adipose tissue, upregulated the production of CD31, upregulated the gene level expression and production of vascular endothelial growth factor (VEGF), indicating the pro-angiogenic effect of 15(S)-HETE. LY294002, an inhibitor of PI3K-Akt pathway, and rapamycin, inhibitor of mammalian target of rapamycin (mTOR), significantly reversed the effect of 15(S)-HETE. 15(S)-HETE also induced activation of Akt and mTOR. These observations suggest that 15(S)-HETE stimulates angiogenesis in adipose tissue through activation of PI3K/Akt/mTOR signaling.

show abstract

12/15-Lipoxygenase signaling in the endoplasmic reticulum stress response

Abstract: Cole BK, Kuhn NS, Green-Mitchell SM, Leone KA, Raab RM, Nadler JL, Chakrabarti SK. 12/15-Lipoxygenase signaling in the endoplasmic reticulum stress response.

Cited by 50 publications

References 45 publications

Cytosolic Phospholipase A ₂ α Is Critical for Angiotensin II–Induced Hypertension and Associated Cardiovascular Pathophysiology

Cytosolic Phospholipase A ₂ α Is Critical for Angiotensin II–Induced Hypertension and Associated Cardiovascular Pathophysiology

Palmitate increases musclin gene expression through activation of PERK signaling pathway in C2C12 myotubes

15(S)-HETE-induced angiogenesis in adipose tissue is mediated through activation of PI3K/Akt/mTOR signaling pathway

Contact Info

Product

Resources

About

12/15-Lipoxygenase signaling in the endoplasmic reticulum stress response

Abstract: Cole BK, Kuhn NS, Green-Mitchell SM, Leone KA, Raab RM, Nadler JL, Chakrabarti SK. 12/15-Lipoxygenase signaling in the endoplasmic reticulum stress response.

Cited by 50 publications

References 45 publications

Cytosolic Phospholipase A 2 α Is Critical for Angiotensin II–Induced Hypertension and Associated Cardiovascular Pathophysiology

Cytosolic Phospholipase A 2 α Is Critical for Angiotensin II–Induced Hypertension and Associated Cardiovascular Pathophysiology

Palmitate increases musclin gene expression through activation of PERK signaling pathway in C2C12 myotubes

15(S)-HETE-induced angiogenesis in adipose tissue is mediated through activation of PI3K/Akt/mTOR signaling pathway

Contact Info

Product

Resources

About

Cytosolic Phospholipase A ₂ α Is Critical for Angiotensin II–Induced Hypertension and Associated Cardiovascular Pathophysiology

Cytosolic Phospholipase A ₂ α Is Critical for Angiotensin II–Induced Hypertension and Associated Cardiovascular Pathophysiology