Functional Coupling Between Various Phospholipase A2s and Cyclooxygenases in Immediate and Delayed Prostanoid Biosynthetic Pathways

Murakami, Makoto; Kambe, Terumi; Shimbara, Satoko; Kudo, Ichiro

doi:10.1074/jbc.274.5.3103

Cited by 342 publications

(438 citation statements)

References 62 publications

(76 reference statements)

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“…Co-transfection experiments demonstrated that COX-1-coupled PG synthesis is favored over COX-2 in the presence of high concentrations of AA. Cytosolic phospholipase A 2 was especially able to drive PG synthesis from COX-1 via an increased supply of AA, which allowed a preferential coupling of COX-1 to membrane-associated PGE synthase 1 activities (35,36). For these reasons, one might hypothesize that basal levels of AA release differ markedly between different tissues and that these differences might be due to tissue-specific differences in phospholipase expression.…”

Section: Discussionmentioning

confidence: 95%

Wound Inflammation in Diabeticob/obMice

et al. 2005

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This study focused on the regulation of prostaglandin (PG) production in diabetes-impaired wound tissue. Cyclooxygenase (COX)-1 and -2 expression and activity were severely dysregulated in chronic wounds of diabetic ob/ob mice. Those wounds were characterized by a reduced expression of COX-1 and the presence of strongly elevated levels of COX-2 when compared with conditions observed in healthy animals. Resolution of the diabetic and impaired wound-healing phenotype by systemic administration of leptin into ob/ob mice increased COX-1 expression in wound margin keratinocytes and decreased COX-2 expression in inner wound areas to levels found in wild-type animals. Notably, improved wound healing was characterized by a marked increase in PGE 2 /PGD 2 biosynthesis that colocalized with induced COX-1 in new tissue at the margin of the wound. COX-2 expression did not significantly contribute to PGE 2 /PGD 2 production in impaired wound tissue. Accordingly, only late wound tissue from SC-560 -treated (selective COX-1 inhibitor) but not celecoxibtreated (selective COX-2 inhibitor) ob/ob mice exhibited a severe loss in PGE 2 , PGD 2 , and prostacyclin at the wound site, and this change was associated with reduced keratinocyte numbers in the neo-epithelia. These data constitute strong evidence that a dysregulation of COX-1-coupled prostaglandin contributes to diabetes-impaired wound healing. Diabetes 54: 1543-1551, 2005

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Section: Discussionmentioning

confidence: 95%

Wound Inflammation in Diabeticob/obMice

et al. 2005

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“…Three major PLA 2 enzymes occur in brainFa Ca 2 þ -dependent cytosolic cPLA 2 selective for AA, a Ca 2 þ -dependent secretory sPLA 2 , and a Ca 2 þ -independent iPLA 2 selective for docosahexaenoic acid (22:6 n-3), another polyunsaturated fatty acid found usually at the sn-2 position of phospholipids (Clark et al, 1995;Dennis, 1994;Murakami et al, 1999;Strokin et al, 2003). Although we do not know which PLA 2 enzymes mediate the k* responses to arecoline and DOI, LiCl feeding to rats is reported to downregulate brain mRNA and activity levels of cPLA 2 but not of sPLA 2 or iPLA 2 (Bosetti et al, 2001;Rintala et al, 1999;Weerasinghe et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Chronic Lithium Administration to Rats Selectively Modifies 5-HT2A/2C Receptor-Mediated Brain Signaling Via Arachidonic Acid

Basselin

Chang

Seemann

et al. 2004

Neuropsychopharmacol

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The effects of chronic lithium administration on regional brain incorporation coefficients k* of arachidonic acid (AA), a marker of phospholipase A 2 (PLA 2 ) activation, were determined in unanesthetized rats administered i.p. saline or 1 mg/kg i.p. (7)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), a 5-HT 2A/2C receptor agonist. After injecting [1-14 C]AA intravenously, k* (brain radioactivity/integrated plasma radioactivity) was measured in each of 94 brain regions by quantitative autoradiography. Studies were performed in rats fed a LiCl or a control diet for 6 weeks. In the control diet rats, DOI significantly increased k* in widespread brain areas containing 5-HT 2A/2C receptors. In the LiCl-fed rats, the significant positive k* response to DOI did not differ from that in control diet rats in most brain regions, except in auditory and visual areas, where the response was absent. LiCl did not change the head turning response to DOI seen in control rats. In summary, LiCl feeding blocked PLA 2 -mediated signal involving AA in response to DOI in visual and auditory regions, but not generally elsewhere. These selective effects may be related to lithium's therapeutic efficacy in patients with bipolar disorder, particularly its ability to ameliorate hallucinations in that disease.

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“…The cDNAs for human mPGES-1 and its mutant R110S (21), human COX-1 and COX-2 (35), and human cPGES (19) were described previously. cDNA probes for human rhoA and human c-myc were donated by Dr. M. Shibanuma (Showa University).…”

Section: Methodsmentioning

confidence: 99%

“…Transfection Studies-Transfection of cDNAs into HEK293 cells was performed by lipofection as described previously (21,35). Briefly, 1 g of plasmid (mPGES-1 in pCDNA3.1/hyg and COX-1 or -2 in pCDNA3.1/neo) was mixed with 2 l of LipofectAMINE 2000 in 100 l of Opti-MEM for 30 min and then added to cells that had attained 40 -60% confluence in 12-well plates (Iwaki Glass) containing 0.5 ml of Opti-MEM.…”

Section: Methodsmentioning

confidence: 99%

Potential Role of Microsomal Prostaglandin E Synthase-1 in Tumorigenesis

Kamei

Murakami

Nakatani

et al. 2003

Journal of Biological Chemistry

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181

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Microsomal prostaglandin E 2 synthase-1 (mPGES-1) is a stimulus-inducible enzyme that functions downstream of cyclooxygenase (COX)-2 in the PGE 2 -biosynthetic pathway. Given the accumulating evidence that COX-2-derived PGE 2 participates in the development of various tumors, including colorectal cancer, we herein examined the potential involvement of mPGES-1 in tumorigenesis. Immunohistochemical analyses demonstrated the expression of both COX-2 and mPGES-1 in human colon cancer tissues. HCA-7, a human colorectal adenocarcinoma cell line that displays COX-2-and PGE 2 -dependent proliferation, expressed both COX-2 and mPGES-1 constitutively. Treatment of HCA-7 cells with an mPGES-1 inhibitor or antisense oligonucleotide attenuated, whereas overexpression of mPGES-1 accelerated, PGE 2 production and cell proliferation. Moreover, cotransfection of COX-2 and mPGES-1 into HEK293 cells resulted in cellular transformation manifested by colony formation in soft agar culture and tumor formation when implanted subcutaneously into nude mice. cDNA array analyses revealed that this mPGES-1-directed cellular transformation was accompanied by changes in the expression of a variety of genes related to proliferation, morphology, adhesion, and the cell cycle. These results collectively suggest that aberrant expression of mPGES-1 in combination with COX-2 can contribute to tumorigenesis.Clinical, genetic, and biochemical evidence has suggested that prostaglandin (PG) 1 E 2 produced via the cyclooxygenase (COX)-2-dependent pathway plays a crucial role in the development of colorectal cancer and possibly other cancers (1). Non-steroidal anti-inflammatory drugs, which inhibit COX-2, reduce the incidence of colorectal cancer (2-4). The major prostanoid produced by several types of cancer is PGE 2 , which is produced by three biosynthetic reactions involving phospholipase A 2 (PLA 2 ), COX, and terminal PGE 2 synthase (PGES). PGE 2 promotes survival and motility of colon cancer cells in vitro and promotes tumorigenesis and angiogenesis in vivo (5-7). High levels of constitutive expression of COX-2 have been found in various cancer cells and tissues (8,9), and studies employing overexpression, antisense suppression, and specific inhibitors of COX-2 have demonstrated that COX-2 contributes to the progression of several types of cancer (10 -12).More direct evidence for the role of COX-2 and its product PGE 2 in colorectal tumorigenesis has been provided by gene targeting studies. Gene disruption of either COX-2 (13) or the PGE receptor EP2 (14) results in reduction of the number and size of intestinal polyps in Apc mutant mice, a model for human familial adenomatous polyposis. In another model, disruption of the genes for the PGE receptors EP1 (15) or EP4 (16) suppresses the development of colorectal cancer induced by carcinogen. Moreover, gene knockout of cytosolic PLA 2 ␣ (cPLA 2 ␣), which supplies the substrate arachidonic acid to COX-2, also leads to reduced polyposis in Apc mutant mice (17,18).PGES catalyzes the conversion of PGH 2 ...

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Functional Coupling Between Various Phospholipase A2s and Cyclooxygenases in Immediate and Delayed Prostanoid Biosynthetic Pathways

Cited by 342 publications

References 62 publications

Wound Inflammation in Diabeticob/obMice

Wound Inflammation in Diabeticob/obMice

Chronic Lithium Administration to Rats Selectively Modifies 5-HT2A/2C Receptor-Mediated Brain Signaling Via Arachidonic Acid

Potential Role of Microsomal Prostaglandin E Synthase-1 in Tumorigenesis

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