Distribution of Group II Phospholipase A2 Protein and mRNA in Rat Tissues

Nyman, Kai; Ojala, Pekka; Laine, V.; Nevalainen, Timo J.

doi:10.1177/002215540004801104

Cited by 23 publications

(21 citation statements)

References 26 publications

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“…PX18 did prevent apoptosis and membrane flip-flop in reversibly damaged cardiomyocytes independent of sPLA 2 -IIA inhibition, as no activity nor expression of sPLA 2 -IIA could be detected in the H9c2 cells under the investigated conditions. This is in agreement with previous studies in which mRNA expression, but no protein expression, of sPLA 2 -IIA was detected in cardiomyocytes [18,19].…”

Section: Discussionsupporting

confidence: 94%

“…PX18 Decreases membrane flip-flop and apoptosis in rat cardiomyoblasts in vitro independent of sPLA 2 -IIA Since RNA expression of sPLA 2 -IIA has been shown in cardiomyocytes under conditions of stress, [18,19] we investigated the putative effect of PX-18 on rat cardiomyoblasts in vitro. Previously, we have found that ischemia resulted mainly in an increase in annexin V/PI positive H9C2 cells (late apoptotic/dead cells), whereas the induced number of single-annexin V positive cells (early apoptotic/ reversibly damaged) was limited [8].…”

Section: Px-18 Reduces Infarct Size and Mortality In A Rat Model Of Amimentioning

confidence: 99%

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Inhibition of type 2A secretory phospholipase A2 reduces death of cardiomyocytes in acute myocardial infarction

et al. 2009

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During acute myocardial infarction (AMI), ischemia leads to necrotic areas surrounded by border zones of reversibly damaged cardiomyocytes, showing membrane flip-flop. During reperfusion type IIA secretory phopholipase A 2 (sPLA 2 -IIA) induces direct cell-toxicity and facilitates binding of other inflammatory mediators on these cardiomyocytes. Therefore, we hypothesized that the specific sPLA 2 -IIA-inhibitor PX-18 would reduce cardiomyocyte death and infarct size in vivo. Wistar rats were treated with PX-18 starting minutes after reperfusion, and at day 1 and 2 post AMI. After 28 days hearts were analyzed. Furthermore, the effect of PX-18 on membrane flipflop and apoptosis was investigated in vitro. PX-18 significantly inhibited sPLA 2 -IIA activity and reduced infarct size (reduction 73 ± 9%, P \ 0.05), compared to the vehicle-treated group, without impairing wound healing. In vitro, PX-18 significantly reduced reversible membrane flip-flop and apoptosis in cardiomyocytes. However, no sPLA 2 -IIA activity could be detected, suggesting that PX-18 also exerted a protective effect independent of sPLA 2 -IIA. In conclusion, PX-18 is a potent therapeutic to reduce infarct size by inhibiting sPLA 2 -IIA, and possibly also by inhibiting apoptosis of cardiomyocytes in a sPLA 2 -IIA independent manner.

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Section: Discussionsupporting

confidence: 94%

Section: Px-18 Reduces Infarct Size and Mortality In A Rat Model Of Amimentioning

confidence: 99%

Inhibition of type 2A secretory phospholipase A2 reduces death of cardiomyocytes in acute myocardial infarction

et al. 2009

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“…sPLA 2 -IIA mRNA has been detected in the normal rat heart (37) and, more specifically, in cardiac myocytes and fibroblasts (38). Although Nyman et al (37) found no evidence of the sPLA 2 enzyme itself in the rat heart, McHowat et al (39) detected sPLA 2 in the cytosolic fraction of the rat heart.…”

Section: Discussionmentioning

confidence: 99%

Antifibrotic Activity of an Inhibitor of Group IIA Secretory Phospholipase A2 in Young Spontaneously Hypertensive Rats

Levick¹,

Loch²,

Rolfe³

et al. 2006

The Journal of Immunology

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The development of fibrosis in the chronically hypertensive heart is associated with infiltration of inflammatory cells and cardiac hypertrophy. In this study, an inhibitor of the proinflammatory enzyme, group IIA human secretory phospholipase A2 (sPLA2-IIA), has been found to prevent collagen deposition as an important component of cardiovascular remodeling in a rat model of developing chronic hypertension. Daily treatment of young male spontaneously hypertensive rats (SHR) with an sPLA2-IIA inhibitor (KH064, 5-(4-benzyloxyphenyl)-4S-(phenyl-heptanoylamino)-pentanoic acid, 5 mg/kg/day p.o.) prevented increases in the content of perivascular (SHR 20.6 ± 0.9%, n = 5; SHR+KH064 14.0 ± 1.2%, n = 5) and interstitial (SHR 7.9 ± 0.3%, n = 6; SHR+KH064 5.4 ± 0.7%, n = 6) collagen in the left ventricle of rat hearts, but did not affect numbers of infiltrating monocytes/macrophages, left ventricular hypertrophy (SHR 2.88 ± 0.08, n = 12; SHR+KH064 3.09 ± 0.08 mg/g body weight, n = 9), increased systolic blood pressure, or thoracic aortic responses. This selective antifibrotic activity suggests that sPLA2-IIA may have an important but specific role in cardiac fibrosis, and that its inhibitors could be useful in dissecting molecular pathways leading to fibrotic conditions.

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“…A similar result has been reported in a different species. sPLA 2 IIA was detected in several rat tissues by immunohistochemistry and Northern blotting, but no in situ hybridization signal was detected (23). Therefore, in the case of this gene, mRNA expression may be below the detection limit of the current methods of tissue preservation and in situ hybridization.…”

Section: Cpla 2 ␦ a Novel Protein In Psoriatic Skinmentioning

confidence: 93%

Cloning of a Gene for a Novel Epithelium-specific Cytosolic Phospholipase A2, cPLA2δ, Induced in Psoriatic Skin

Chiba

Michibata

Wakimoto

et al. 2004

Journal of Biological Chemistry

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Psoriasis is a common skin disease characterized by hyperplastic regenerative epidermal growth and infiltration of immunocytes. The etiology of psoriasis is unknown, although several genetic and cellular factors have been elucidated. To find new psoriasis-related genes, we have cloned cDNAs that are differentially expressed between normal and psoriatic skins. Among these clones, we have identified a new gene that codes for a new member of the type IV cytosolic phospholipase A 2 (cPLA 2 ) family. We refer to this gene as cPLA 2 ␦. It encodes a polypeptide of 818 amino acids that has significant homology with known cPLA 2 proteins in the C2 and catalytic domains. The cPLA 2 ␦ gene was mapped to the 15q13-14 chromosomal locus, near to the locus of the cPLA 2 ␤ gene, from which it is separated by a physical distance of about 220 kb. To identify the phospholipase A 2 activity of cPLA 2 ␦, we transfected COS-7 cells with His-tagged cPLA 2 ␦. The cell lysate from these cells had calcium-dependent phospholipase A 2 activity. Northern blot analysis revealed that a cPLA 2 ␦ transcript of about 4 kb is expressed in stratified squamous epithelia, such as those in skin and cervix, but not in other tissues. In situ hybridization and immunohistochemistry revealed that cPLA 2 ␦ is expressed strongly in the upper spinous layer of the psoriatic epidermis, expressed weakly and discontinuously in atopic dermatitis and mycosis fungoides, and not detected in the epidermis of normal skin; cPLA 2 ␣ is not detected in either normal or psoriatic skin. These results suggest that cPLA 2 ␦ exhibits a unique distribution pattern compared with that of known cPLA 2 subtypes, and it may play a critical role in inflammation in psoriatic lesions.

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Distribution of Group II Phospholipase A2 Protein and mRNA in Rat Tissues

Cited by 23 publications

References 26 publications

Inhibition of type 2A secretory phospholipase A2 reduces death of cardiomyocytes in acute myocardial infarction

Inhibition of type 2A secretory phospholipase A2 reduces death of cardiomyocytes in acute myocardial infarction

Antifibrotic Activity of an Inhibitor of Group IIA Secretory Phospholipase A2 in Young Spontaneously Hypertensive Rats

Cloning of a Gene for a Novel Epithelium-specific Cytosolic Phospholipase A2, cPLA2δ, Induced in Psoriatic Skin

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