Dependence of thymocyte apoptosis on protein kinase C and phospholipase A<sub>2</sub>

Shaposhnikova, V. V.; Dobrovinskaya, Oxana; Eidus, L.Kh.; Korystov, Yuri N.

doi:10.1016/0014-5793(94)00616-4

Cited by 27 publications

(16 citation statements)

References 20 publications

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“…This control confirmed that NDGA affects apoptosis via lipoxygenase inhibition. Taken together these data and the apoptosis prevention with the PLA2 inhibitor [5,14] 1, control; 2, 6 Gy; 3, 6 Gy+l gM indomethacin; 4, 6 Gy+10 gM indomethacin; 5, 6 Gy+100 I.tM indomethacin; 6, 6 Gy+20 gM NDGA; 7, 40 gM NDGA; 8, 6 Gy+40 gM NDGA. n = 3~.…”

Section: Resultsmentioning

confidence: 58%

“…The released AA is consequently oxidized either by cyclooxygenase with formation of cyclic products like prostaglandins, or by lipoxygenase giving rise to linear chain products such as lipoxines and leukotrienes [8,13]. Previously we have shown that BPB, a PLA2 inhibitor [11], prevents nuclear pycnosis [5] and DNA fragmentation [14] in irradiated thymocytes. Nuclear pycnosis was the only criterion of the effects of lipoxygenase and cyclooxygenase inhibitors [5].…”

Section: Introductionmentioning

confidence: 99%

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Role of arachidonic acid metabolism in thymocyte apoptosis after irradiation

et al. 1996

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The present study demonstrates that DNA fragmentation, nuclear pycnosis and trypan blue staining of irradiated thymocytes is prevented by inhibition of the lipoxygenase pathway of arachidonic acid metabolism and is not affected by cyclooxygenase inhibition. Exposed to irradiation [3H]arachidonic acid-labeled thymocytes release radioactive products to the external medium. The process is blocked by the lipoxygenase inhibitor, nordihydroguaiaretic acid. Thus, it can be concluded that irradiation activates arachidonic acid metabolism and that lipoxygenase metabolites play an important role in thymocyte apoptosis.

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Section: Resultsmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Role of arachidonic acid metabolism in thymocyte apoptosis after irradiation

et al. 1996

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“…but the molecular nature of these PLA 2 s has not been identified (78,79). The biological role of PLA 2 activity in thymus is poorly understood, although certain reports suggest a role in rat thymocyte apoptosis (80,81). Interestingly, p-bromophenacyl bromide, a known inhibitor of sPLA 2 s (14,30,82,83), prevents apoptosis of rat thymocytes and lymphoma cells (84).…”

Section: Figmentioning

confidence: 99%

Cloning, Chromosomal Mapping, and Expression of a Novel Human Secretory Phospholipase A2

Cupillard¹,

Koumanov²,

Matteï³

et al. 1997

Journal of Biological Chemistry

246

250

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Secretory phospholipases A 2 (sPLA 2 s) represent a rapidly expanding family of structurally related enzymes found in mammals as well as in insect and snake venoms. In this report, a cDNA coding for a novel sPLA 2 has been isolated from human fetal lung, and its gene has been mapped to chromosome 16p13.1-p12. The mature sPLA 2 protein has a molecular mass of 13.6 kDa, is acidic (pI 5.3), and made up of 123 amino acids. Key structural features of the sPLA 2 include: (i) a long prepropeptide ending with an arginine doublet, (ii) 16 cysteines located at positions that are characteristic of both group I and group II sPLA 2 s, (iii) a C-terminal extension typical of group II sPLA 2 s, (iv) and the absence of elapid and pancreatic loops that are characteristic of group I sPLA 2 s. Based on these structural properties, this sPLA 2 appears as a first member of a new group of sPLA 2 s, called group X. A 1.5-kilobase transcript coding for the human group X (hGX) sPLA 2 was found in spleen, thymus, and peripheral blood leukocytes, while a less abundant 0.8-kilobase transcript was detected in the pancreas, lung, and colon. When the hGX sPLA 2 cDNA was expressed in COS cells, sPLA 2 activity preferentially accumulated in the culture medium, indicating that hGX sPLA 2 is an actively secreted enzyme. It is maximally active at physiological pH and with 10 mM Ca 2؉ . hGX sPLA 2 prefers phosphatidylethanolamine and phosphatidylcholine liposomes to those of phosphatidylserine.

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“…During the progression of sepsis, thymic atrophy is induced via apoptosis (46). Because several reports suggest an involvement of PLA 2 in thymocyte apoptosis (47,48), the novel sPLA 2 might play a role in this process. The expression of novel sPLA 2 mRNA was also changed in rat lung after LPS treatment, but its pattern was different from the case of group IIA sPLA 2 .…”

Section: Molecular Cloning Of Novel Splamentioning

confidence: 99%

“…Recombinant Expression of Novel sPLA 2 s and Characterization of sPLA 2 Activity-The deduced amino acid sequences from both mouse and human novel sPLA 2 cDNA contain all of the amino acids that are absolutely conserved in all functional sPLA 2 s including His 48 and Asp 49 . Therefore, they were expected to possess enzymatic activities, which should be exported extracellularly after cleavage from the presumed signal peptide.…”

Section: Molecular Cloning Of Novel Splamentioning

confidence: 99%

Cloning and Characterization of Novel Mouse and Human Secretory Phospholipase A2s

Ishizaki

Suzuki

Higashino

et al. 1999

Journal of Biological Chemistry

137

104

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Mammalian secretory phospholipase A 2 s (sPLA 2 s) are classified into several groups according to molecular structure and the localization of intramolecular disulfide bridges. Among them, group IIA sPLA 2 has been thought to be one of the key enzymes in the pathogenesis of inflammatory diseases owing to its augmented expression under various inflammatory conditions. However, in a number of inbred mouse strains, the group IIA sPLA 2 gene is naturally disrupted by a frameshift mutation. Here, we report the cloning of a cDNA encoding a novel sPLA 2 expressed in the spleen of group IIA sPLA 2 -deficient mouse. We also cloned its human homolog and mapped its gene location on chromosome 1p36.12 near the loci of group IIA and V sPLA 2 genes. The human mature sPLA 2 protein consists of 125 amino acids (M r ‫؍‬ 14,500) preceded by a 20-residue prepeptide and is most similar to group IIA sPLA 2 with respect to the number and positions of cysteine residues as well as overall identity (48%). Based on these structural properties, the novel sPLA 2 should be categorized into group II, called group IID to follow the already identified IIA to IIC sPLA 2 s. When the cDNA was expressed in COS-7 cells, PLA 2 activity preferentially accumulated in the culture medium. It is maximally active at neutral to alkaline pH and with 2 mM Ca 2؉ . In assays with individual substrates, L-␣-1-palmitoyl-2-linoleoyl phosphatidylethanolamine was more efficiently hydrolyzed than the other phospholipids examined. An RNA blot hybridized with the cDNA exhibited two transcripts (2.0 and 1.0 kb) in human spleen, thymus, and colon. The expression of a novel sPLA 2 mRNA was elevated in the thymus after treatment with endotoxin in rats as well as in group IIA sPLA 2 -deficient mice, suggesting its functional role in the progression of the inflammatory process.

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Dependence of thymocyte apoptosis on protein kinase C and phospholipase A₂

Cited by 27 publications

References 20 publications

Role of arachidonic acid metabolism in thymocyte apoptosis after irradiation

Role of arachidonic acid metabolism in thymocyte apoptosis after irradiation

Cloning, Chromosomal Mapping, and Expression of a Novel Human Secretory Phospholipase A2

Cloning and Characterization of Novel Mouse and Human Secretory Phospholipase A2s

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Dependence of thymocyte apoptosis on protein kinase C and phospholipase A2

Cited by 27 publications

References 20 publications

Role of arachidonic acid metabolism in thymocyte apoptosis after irradiation

Role of arachidonic acid metabolism in thymocyte apoptosis after irradiation

Cloning, Chromosomal Mapping, and Expression of a Novel Human Secretory Phospholipase A2

Cloning and Characterization of Novel Mouse and Human Secretory Phospholipase A2s

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Dependence of thymocyte apoptosis on protein kinase C and phospholipase A₂