'Phosphatidylcholine (PtdCho) is a major membrane phospholipid, and its loss is sufficient in itself to induce cell death. PtdCho homeostasis is regulated by the balance between hydrolysis and synthesis. PtdCho is hydrolyzed by phospholipase A2 (PLA2), PtdChospecific phospholipase C (PtdCho-PLC), and phospholipase D (PLD). PtdCho synthesis is rate-limited by CTP:phosphocholine ... More
The antisignaling agent SC-alpha alpha delta 9, 4-(benzyl-(2-[(2,5-diphenyloxazole-4-carbonyl)amino]ethyl)carbamoyl)- 2-decanoylaminobutyric acid, is a structurally unique phospholipid analogue with phospholipase C inhibitory activity.
AuthorsVogt A, Pestell KE, Day BW, Lazo JS, Wipf P,
JournalMol Cancer Ther
PubMed ID12481409
'Phospholipids and lipid second messengers mediate mitogenic signal transduction and oncogenesis, but there have been few successful examples of small molecules that affect biologically important phospholipid metabolism. Here we investigated the actions of a previously described antitumor agent, 4-(benzyl-(2-[(2,5-diphenyloxazole-4-carbonyl)amino]ethyl)carbamoyl)- 2-decanoylaminobutyric acid (SC-alpha alpha delta 9), which has antisignaling properties, on ... More
Defective coupling of apical PTH receptors to phospholipase C prevents internalization of the Na+-phosphate cotransporter NaPi-IIa in Nherf1-deficient mice.
AuthorsCapuano P, Bacic D, Roos M, Gisler SM, Stange G, Biber J, Kaissling B, Weinman EJ, Shenolikar S, Wagner CA, Murer H
JournalAm J Physiol Cell Physiol
PubMed ID16987995
'Phosphate reabsorption in the renal proximal tubule occurs mostly via the type IIa Na(+)-phosphate cotransporter (NaP(i)-IIa) in the brush border membrane (BBM). The activity and localization of NaP(i)-IIa are regulated, among other factors, by parathyroid hormone (PTH). NaP(i)-IIa interacts in vitro via its last three COOH-terminal amino acids with the ... More
Enzymatic measurement of phosphatidylserine in cultured cells.
Phosphatidylserine (PS) is a quantitatively minor membrane phospholipid involved in diverse cellular functions. In this study, we developed a new fluorometric method for measuring PS using combinations of specific enzymes and Amplex Red. The calibration curve for PS measurement was linear and hyperbolic at low (0-50 µM) and high (50-1000 ... More
Phosphatidylcholine-specific phospholipase C activation is required for CCR5-dependent, NF-kB-driven CCL2 secretion elicited in response to HIV-1 gp120 in human primary macrophages.
CCL2 (MCP-1) has been shown to enhance HIV-1 replication. The expression of this chemokine by macrophages is up-modulated as a consequence of viral infection or gp120 exposure. In this study, we show for the first time that the phosphatidylcholine-specific phospholipase C (PC-PLC) is required for the production of CCL2 triggered ... More
Lipid-modifying enzymes in human tear fluid and corneal epithelial stress response.
AuthorsRobciuc A, Rantamäki AH, Jauhiainen M, Holopainen JM,
Journal
PubMed ID24302584
Since homeostasis at the ocular surface requires a delicate balance between numerous factors, and the external environment contributes as an unpredictable component, we aimed to understand the role that various lipids and their regulators have in the complex process that maintains a healthy corneal surface. Through basic proteomics, we tested ... More
Guanosine 5'-[gamma-thio]triphosphate-mediated activation of cytosol phospholipase C caused lysosomal destabilization.
AuthorsWang X, Wang LL, Zhang GJ
JournalJ Membr Biol
PubMed ID16988860
Lysosomal disintegration is critical for the organelle functions and cellular viability. In this study, we established that guanosine 5'-[gamma-thio]triphosphate (GTP-gamma-S)-activated cytosol of rat hepatocytes could increase lysosomal permeability to both potassium ions and protons and osmotically destabilize the lysosomes via K(+)/H(+) exchange. These results were obtained through measurements of lysosomal ... More
Expression and role of phosphatidylcholine-specific phospholipase C in human NK and T lymphocyte subsets.
AuthorsSpadaro F, Cecchetti S, Sanchez M, Ausiello CM, Podo F, Ramoni C
JournalEur J Immunol
PubMed ID17111345
We recently reported evidence of phosphatidylcholine-specific phospholipase C (PC-PLC) involvement in NK cell-mediated cytotoxicity and in lytic granule exocytosis. In the present study, different subpopulations of human PBL were investigated in relation to PC-PLC enzyme expression. While a substantial intracellular amount of PC-PLC was detected in all lymphoid subsets, expression ... More
Involvement of phosphatidylcholine-selective phospholipase C in activation of mitogen-activated protein kinase pathways in imidazoline receptor antisera-selected protein.
AuthorsLi F, Wu N, Su RB, Zheng JQ, Xu B, Lu XQ, Cong B, Li J
JournalJ Cell Biochem
PubMed ID16598778
Imidazoline receptor antisera-selected protein (IRAS) is considered as a candidate for the I1-imidazoline receptor (I1R), but the signaling pathway mediated by IRAS remains unknown. In our study, the signal transduction pathways of IRAS were investigated in CHO cells stably expressing IRAS (CHO-IRAS), and compared to the native I1R signaling pathways. ... More
Phospholipases C and A2 control lysosome-mediated IL-1 beta secretion: Implications for inflammatory processes.
AuthorsAndrei C, Margiocco P, Poggi A, Lotti LV, Torrisi MR, Rubartelli A
JournalProc Natl Acad Sci U S A
PubMed ID15192144
Blocking the activity of IL-1 beta has entered the clinical arena of treating autoimmune diseases. However, a successful outcome of this approach requires a clear definition of the mechanisms controlling IL-1 beta release. These are still unclear as IL-1 beta, lacking a secretory signal peptide, follows a nonclassical pathway of ... More
Coupling of I(1) imidazoline receptors to the cAMP pathway: studies with a highly selective ligand, benazoline.
AuthorsGreney H, Ronde P, Magnier C, Maranca F, Rascente C, Quaglia W, Giannella M, Pigini M, Brasili L, Lugnier C, Bousquet P, Dontenwill M
JournalMol Pharmacol
PubMed ID10825384
Clonidine and benazoline are two structurally related imidazolines. Whereas clonidine binds both to alpha(2)-adrenoceptors (alpha(2)R) and to I(1) imidazoline receptors (I(1)R), benazoline showed a high selectivity for imidazoline receptors. Although the alpha(2)R are negatively coupled to adenylate cyclase, no effect on cAMP level by activation of I(1)R has been reported ... More
CD38 signaling regulates B lymphocyte activation via a phospholipase C (PLC)-gamma 2-independent, protein kinase C, phosphatidylcholine-PLC, and phospholipase D-dependent signaling cascade.
AuthorsMoreno-García ME, López-Bojórques LN, Zentella A, Humphries LA, Rawlings DJ, Santos-Argumedo L
JournalJ Immunol
PubMed ID15728476
The CD38 cell surface receptor is a potent activator for splenic, B lymphocytes. The molecular mechanisms regulating this response, however, remain incompletely characterized. Activation of the nonreceptor tyrosine kinase, Btk, is essential for CD38 downstream signaling function. The major Btk-dependent substrate in B cells, phospholipase C-gamma2 (PLC-gamma2), functions to generate ... More
Acidic extracellular pH induces matrix metalloproteinase-9 expression in mouse metastatic melanoma cells through the phospholipase D-mitogen-activated protein kinase signaling.
AuthorsKato Y, Lambert CA, Colige AC, Mineur P, Noël A, Frankenne F, Foidart JM, Baba M, Hata R, Miyazaki K, Tsukuda M
JournalJ Biol Chem
PubMed ID15657063
The extracellular pH (pHe) of tumor tissues is often acidic, which can induce the expression of several proteins. We previously showed that production of matrix metalloproteinase-9 (MMP-9) was induced by culturing cells at acidic pHe (5.4-6.5). Here we have investigated the signal transduction pathway by which acidic pHe induces MMP-9 ... More