Phosphatidylcholines apoptosis

Figure 3. Inhibition of phosphatidylcholine biosynthesis by apoptosis-inducing compounds. The target enzyme for the inhibition of PC biosynthesis is shown for several compounds that have further in common that they all induce apoptosis. Abbreviations are as follows CK, choline kinase CPT, cholinephosphotransferase CT, CTP phosphocholine cytidylyltransferase PC, phosphatidylcholine.

Anthony, M.L., Zhao, M., and Brindle, K.M., 1999, Inhibition of phosphatidylcholine biosynthesis following induction of apoptosis in HL-60 cells. J. Biol. Chem. 274 19686-19692... 

Bettaieb, A., Plo, 1., Mansat-de Mas, V., Quillet-Mary, A., Levade, T., Laurent, G., and Jaffrezou, J-P., 1999, Daunorubicin- and Mitoxantrone-tiiggered phosphatidylcholine hydrolysis implication in drug-induced ceramide generation and apoptosis. Mol. Pharm. 55 118-125... 

Wright, M.M., Henneberry, A.L., Lagace, T.A., Ridgway, N.D., and McMaster, C.R., 2001, Uncouphng Famesol Induced Apoptosis from its Inhibition of Phosphatidylcholine Synthesis. . Biol Chem. 276 25254-25261. 

Yen, C.L., Mar, M.H., and Zeisel, S.H., 1999, Chohne dehdency-induced apoptosis in PC12 ceUs is associated with diminished membrane phosphatidylcholine and sphingomyelin, accumulation of ceramide and diacylglycetol, and achvation of a caspase. FASEB. J. 13 135-142... 

Hossain, Z., Konishi, M., Hosokawa, M., and Takahashi, K. (2006). Effect of polyunsaturated fatty acid-enriched phosphatidylcholine and phosphatidylserine on butyrate-induced growth inhibition, differentiation and apoptosis in Caco-2 cells. Cell Biochem. Fund. 24, 159-165. 

Miquel, K., Pradines, A., Terce, F., Selmi, S., and Favre, G., 1998, Competitive inhibition of choline phosphotransferase by geranylgeraniol and famesol inhibits phosphatidylcholine synthesis and induces apoptosis in human lung adenocarcinoma A549 cells. JBiol Chem. 273 26179-26186... 

Inhibition of SM synthase. Tricyclodecan-9-yl xan-thogenate (D609, Fig. 12) is a known inhibitor of phospholipase C (which hydrolyzes phosphatidylcholine) (127). It inhibited SM synthase and induced apoptosis in U937 human monocytic leukemia cells (128) and rat PC12 cells (129). 

Cui, Z., Houwehng, M., Chen, M.H., Record, M., Chap, H., Vance, D.E., and Terce, F. (1996). A genetic defect in phosphatidylcholine hios3mthesis triggers apoptosis in Chinese hamster ovary cells. J Biol Chem 111, 14668-71. 

Ramos, B., Salido, G.M., Campo, M.L., and Claro, E. (2000). Inhibition of phosphatidylcholine synthesis precedes apoptosis induced by C2-ceramide protection by exogenous phosphatidylcholine. Neuroreport 11, 3103-8. 

Fig. 4.4 Involvement of Fas and NMDA receptors in apoptotic and necrotic cell death. Fas ligand (FasL) Fas receptor (Fas-R) IV-methyl-D-aspartate receptor (NMDA-R) phosphatidylcholine (PtdCho) cytosolic phospholipase A2 (CPLA2) arachidonic add (ARA) arginine (Arg) nitric oxide synthase (NOS) nitric oxide (NO) superoxide (O2) peroxynitrite (ONOO ) arachidonic add (ARA) lyso-phosphatidylcholine (lyso-PtdCho) platelet-activating factor (PAF) cytochrome c (Cytc) apoptosome complex with apoptosis-activating factor-1 (Apaf-1) and poly(ADP)ribose polymerase (PARP) secretory phospholipase (SPLA2) inducible nitric oxide synthase (iNOS) cyclooxygenase-2 (COX-2) matrix metalloproteinase (MMP) nuclear factor-kappa B (NF-kB) inhibitory form of nuclear factor kappa B (I-kB/NF-kB) nuclear factor xB-response element (NF-kB-RE) inhibitory subunit of NF-kB (I-kB) tumor necrosis factor-a (TNF-a) interleukin-ip (IL-ip) and interleukin-6 (IL-6)...

Fig. 7.9 Generation of JV-acylethanolamine (NAE) and A-acylphosphatidylethanolamine (NAPE) in brain. Phosphatidylcholine (PtdCho) phosphatidylethanolamine (PtdEtn) cannabinoid lecep-torl (CBj-R) JV-methyl-D-aspartate receptor (NMDA-R) tmandamide and 2-arachidonyl-gltcerol not only stimulate CBi-R but also have stabilizing effects on neural membranes. TBI increases the formation of NAE and NAPE. Ai-arachidonylethanolamine stimulate ceramide formation, N-acylethanolamine inhibit ceramidase. Ceramide induces apoptosis. Plus sign indicate stimulation and minus sign indicates inhibition, (f) Indicate increase in levels...

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