High‐affinity binding sites for 12(<i>S</i>)‐hydroxy‐5,8,10,14‐eicosatetraenoic acid (12(<i>S</i>)‐HETE) in carcinoma cells

Herbertsson, Helena; Hammarström, Sven

doi:10.1016/0014-5793(92)80069-s

Cited by 28 publications

(10 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Little is known about the receptors and related signaling pathways for HETEs and HODEs, although high-affinity binding sites for 12(S)-HETE have been described for several cell lines (28)(29)(30). In the present study using B16a cells, we report the existence of specific high-affinity binding sites for 12(S)-HETE.…”

Section: Regulation Of Pkc-a By 12(s)-hete and 13(s)-hodesupporting

confidence: 48%

12(S)-hydroxyeicosatetraenoic acid and 13(S)-hydroxyoctadecadienoic acid regulation of protein kinase C-alpha in melanoma cells: role of receptor-mediated hydrolysis of inositol phospholipids.

Liu

Khan

Hannun

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

100

View full text Add to dashboard Cite

Protein kinase C (PKC) isoenzymes are essential components of cell signaling. In this study, we investigated the regulation of PKC-a in murine B16 amelanotic melanoma (B16a) Inhibitor studies revealed that PKC was involved in basal and 12(S)-HETE-regulated tumor cell and endothelial cell integrin expression (5), adhesion (6, 7), spreading (5), and experimental metastasis (7). However, the involvement of specific PKC isoform(s) and particularly the related mechanism(s) of action for 12(S)-HETE and 13(S)-HODE have not been explored.Previously, exploration of mechanisms of action for monoHETEs placed emphasis on investigating their fate after uptake by cells and their intracellular targets. For example, extracellular mono-HETEs are esterified into phospholipids, possibly affecting certain membrane functions (8). In vitro kinase assays revealed that 15-HETE can increase PKC activity (9), and 12-HETE can activate PKC-y (10). Finally, incorporated 12(S)-HETE has been shown to bind to an intracellular protein (11). Although receptors have been identified for some eicosanoids (12-18), studies on possible cell membrane receptor-mediated signaling processes for 12(S)-HETE and/or 13(S)-HODE are lacking. In this study, we propose that 12(S)-HETE and 13(S)-HODE interact with a cell surface receptor(s) whose activation leads to generation of second messengers and further downstream activation of PKC.Protein kinase C (PKC) consists of a family of protein-serine/ threonine kinases that play important roles in mediating cell growth, differentiation, and tumor promotion (1). Binding of extracellular stimulators (e.g., hormones, growth factors, cytokines, and neurotransmitters) to their cell surface receptors triggers the phospholipase C (PLC)-mediated hydrolysis of phosphatidylinositol bisphosphate, generating the second messengers diacylglycerol (DAG) and D-myo-inositol 1,4,5-trisphosphate (IP3). While DAG directly activates PKC, IP3 releases Ca2+ from intracellular stores (1). Tumor-promoting phorbol esters, such as phorbol 12-myristate 13-acetate (PMA), mimic DAG and directly activate PKC.Metastasis is a multistep process involving tumor cell detachment from the primary tumor, invasion through basement membrane, and intravasation (2). Once blood borne, the tumor cell must adhere to endothelium, induce endothelial cell retraction, and again invade through basement membrane to form a successful secondary tumor. Previously, we have observed that the ability of tumor cells to accomplish many of these steps in the metastatic cascade is enhanced by 12(S)- MATERIALS AND METHODSMaterials. Polyclonal antibodies against PKC-a, -P3I, -,BII, -ry, -8, -a, or -(were prepared as described (19). PMA, pertussis toxin, and cholera toxin were obtained from Calbiochem. Genistein was purchased from Sigma. 12(S)-[3H]HETE (215.3 Ci/mmol; 1 Ci = 37 GBq) was from NEN. Murine B16 amelanotic melanoma (B16a) cells were maintained as described (5). Subcellular Fractionation, PKC Activity Assay, and Western Blotting. Cytosol and membrane PKC wer...

show abstract

Section: Regulation Of Pkc-a By 12(s)-hete and 13(s)-hodesupporting

confidence: 48%

12(S)-hydroxyeicosatetraenoic acid and 13(S)-hydroxyoctadecadienoic acid regulation of protein kinase C-alpha in melanoma cells: role of receptor-mediated hydrolysis of inositol phospholipids.

Liu

Khan

Hannun

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

100

View full text Add to dashboard Cite

show abstract

“…In contrast, the stereoisomer 12(R)-HETE, which is not an LO product, did not have these stimulatory effects, indicating specificity for the LO pathway. Although there is evidence in other cell types for a 12(S)-HETE receptor (37,38), it is not clear from this study whether the effects of 12(S)-HETE on Ras-MAPK activation are mediated by a specific receptor. Because 12(S)-HETE did not directly induce oxidant stress in these cells, 2 additional unknown mechanisms for MAPK activation may be operative.…”

Section: Discussionmentioning

confidence: 64%

The Oxidized Lipid and Lipoxygenase Product 12(S)-Hydroxyeicosatetraenoic Acid Induces Hypertrophy and Fibronectin Transcription in Vascular Smooth Muscle Cells via p38 MAPK and cAMP Response Element-binding Protein Activation

Reddy¹,

Thimmalapura²,

Lanting³

et al. 2002

Journal of Biological Chemistry

126

137

View full text Add to dashboard Cite

Growth factor-and cytokine-induced vascular smooth muscle cell proliferation, migration, hypertrophy, and matrix production have been shown to play important roles in the development of vascular disorders such as atherosclerosis, hypertension, and restenosis. Growth factors such as angiotensin II (AngII) 1 and platelet-derived growth factor (PDGF) activate intracellular phospholipases, leading to the formation of arachidonic acid, which can be further metabolized by cyclooxygenases, cytochrome P-450 oxygenases, and lipoxygenases (1). Lipoxygenase (LO) action leads to the formation of oxidized lipids such as 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE). LOs and their products of arachidonic acid and linoleic acid metabolism have been shown to mediate growth factor effects in vascular smooth muscle cells (VSMCs) as well as responses to vascular injury. Lipoxygenases are classified as 5-, 8-, 12-, and 15-lipoxygenases based on their ability to insert molecular oxygen at the corresponding carbon atom of arachidonic acid. Three major isoforms of 12-LO have been cloned. They are platelet-type 12-LO, leukocyte-type 12-LO, and epidermis-type 12-LO. These proteins are products of distinct genes and vary in tissue distribution (2, 3).Leukocyte 12-LO has been cloned from porcine and mouse leukocytes (4, 5). The presence of leukocyte-type 12-LO (also termed 12/15-LO) has also been demonstrated in various cell types and tissues, including VSMCs, adrenal cells, rat brain, and kidney (6 -11). Studies from this and other laboratories (12-21) have implicated the leukocyte-type 12-LO pathway in the pathogenesis of atherosclerosis and restenosis. 12-LO expression was demonstrated in atherosclerotic lesions (12). In vascular and mononuclear cells, growth factors and cytokines as well as high glucose stimulate both the activity and expression of 12-LO (6, 13-15). Furthermore, expression of 12-LO protein and mRNA is markedly increased in neointima of balloon-injured rat carotid arteries, and pretreatment with LO inhibitors reduces the rate of neointimal thickening in this model (16,17). We have demonstrated that treatment with a chimeric DNA-RNA hammerhead ribozyme targeted to cleave rat leukocyte-type 12-LO mRNA significantly reduces neointimal thickening in balloon-injured rat arteries (18). We have

show abstract

“…There are other studies that suggest a putative receptor for 12(S)-HETE. Highaffinity binding sites have been observed on some cell types, 38,39 suggesting a possible role for 12(S)-HETE as a signaling ligand.…”

Section: Discussionmentioning

confidence: 99%

Lipoxygenase Products Increase Monocyte Adhesion to Human Aortic Endothelial Cells

Patricia

Kim

Harper

et al. 1999

ATVB

113

105

View full text Add to dashboard Cite

Abstract-The development of atherosclerosis is accelerated in individuals with type 2 diabetes. Adhesion of monocytes to the vascular endothelium is a key initial step in atherogenesis. We have previously shown that monocyte adhesion to human aortic endothelial cells (HAECs) cultured long-term in high-glucose medium (25 mmol/L, 2 passages) is increased compared with cells grown in normal glucose (5 mmol/L). One potential mechanism for increased monocyte adhesion to HAECs under hyperglycemic conditions is via the 12-lipoxygenase (12-LO) pathway. In this study, we demonstrated in HAECs that the major LO metabolite of arachidonic acid was the 12-LO product, 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], which was increased severalfold in HAECs cultured under high-glucose conditions. Furthermore, treatment of HAECs with 12(S)-HETE induced monocyte, but not neutrophil, adhesion an average of 3-fold (range of 1.5-to 5-fold) compared with untreated cells (75Ϯ5 versus 26Ϯ1 monocytes per field, respectively, PϽ0.001). Expression of the adhesion molecules vascular cell adhesion molecule-1, E-selectin, and intercellular adhesion molecule-1 was not significantly increased. However, both glucose and 12(S)-HETE induced a 60% increase in HAEC surface expression of connecting segment-1 (ie, CS-1) fibronectin, a ligand for very late-acting antigen-4 (VLA-4). The antibodies used to block monocyte integrin VLA-4 and leukocyte function-related antigen-1, a monocytic counterreceptor for intercellular adhesion molecule-1, inhibited the ability of both 12-LO products and high glucose to induce monocyte adhesion. These results definitively demonstrate for the first time in HAECs that the 12-LO pathway can induce monocyte-endothelial cell interaction and that the effects of glucose may be mediated, at least in part, through this pathway. Thus, these results suggest that the 12-LO pathway may play a role in the increased susceptibility of diabetics to atherosclerosis.

show abstract

High‐affinity binding sites for 12(S)‐hydroxy‐5,8,10,14‐eicosatetraenoic acid (12(S)‐HETE) in carcinoma cells

Cited by 28 publications

References 18 publications

12(S)-hydroxyeicosatetraenoic acid and 13(S)-hydroxyoctadecadienoic acid regulation of protein kinase C-alpha in melanoma cells: role of receptor-mediated hydrolysis of inositol phospholipids.

12(S)-hydroxyeicosatetraenoic acid and 13(S)-hydroxyoctadecadienoic acid regulation of protein kinase C-alpha in melanoma cells: role of receptor-mediated hydrolysis of inositol phospholipids.

The Oxidized Lipid and Lipoxygenase Product 12(S)-Hydroxyeicosatetraenoic Acid Induces Hypertrophy and Fibronectin Transcription in Vascular Smooth Muscle Cells via p38 MAPK and cAMP Response Element-binding Protein Activation

Lipoxygenase Products Increase Monocyte Adhesion to Human Aortic Endothelial Cells

Contact Info

Product

Resources

About