Role of ceramide in Ca2+-sensing receptor-induced apoptosis

Wu, Zhenzhen; Tandon, Rajnish; Ziembicki, Jenny; Nagano, Junko; Hujer, Kristine M.; Miller, R. Tyler; Huang, Changcheng

doi:10.1194/jlr.m500071-jlr200

Cited by 17 publications

(13 citation statements)

References 49 publications

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“…Our laboratory and others have also shown that alterations of the SMaseceramide pathway may be associated with tumorigenesis [48,86,87]. For example, as noted above, Ilsley et al [48] established an association between reduced ceramide production and diminished apoptosis in carcinogen-induced colon tumors, a finding that was restricted to cPLA 2 α-deficient mice.…”

Section: Activation Of the Smase-ceramide Pathway By Aamentioning

confidence: 68%

“…For example, as noted above, Ilsley et al [48] established an association between reduced ceramide production and diminished apoptosis in carcinogen-induced colon tumors, a finding that was restricted to cPLA 2 α-deficient mice. In addition, Wu et al [87] showed that the growth inhibitory effects of omega-3 polyunsaturated fatty acids on breast tumor xenografts were correlated with elevated activity of the neutral SMase isoform. Moreover, reduced activity of the intestinal-specific alkaline SMase has been reported in human colorectal tumors [88,89].…”

Section: Activation Of the Smase-ceramide Pathway By Aamentioning

confidence: 99%

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Roles of cPLA2α and arachidonic acid in cancer

Nakanishi

Rosenberg

2006

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

103

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Phospholipase A 2 s (PLA 2 s) are key enzymes that catalyze the hydrolysis of membrane phospholipids to release bioactive lipids that play an important role in normal cellular homeostasis. Under certain circumstances, disrupted production of key lipid mediators may adversely impact physiological processes, leading to pathological conditions such as inflammation and cancer. In particular, cytosolic PLA 2 α (cPLA 2 α) has a high selectivity for liberating arachidonic acid (AA) that is subsequently metabolized by a panel of downstream enzymes for eicosanoid production. Although concentrations of free AA are maintained at low levels in resting cells, alterations in AA production, often resulting from dysregulation of cPLA 2 α activity, are observed in transformed cells. In this review, we summarize recent evidence that cPLA 2 α plays a role in the pathogenesis of many human cancers. Much of this evidence has been accumulated from functional studies using cPLA 2 α-deficient mice, as well as mechanistic studies in cell culture. We also discuss the potential contribution of cPLA 2 α and AA to apoptosis, and the regulatory mechanisms leading to aberrant expression of cPLA 2 α.

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Section: Activation Of the Smase-ceramide Pathway By Aamentioning

confidence: 68%

Section: Activation Of the Smase-ceramide Pathway By Aamentioning

confidence: 99%

Roles of cPLA2α and arachidonic acid in cancer

Nakanishi

Rosenberg

2006

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

103

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“…It should be pointed out that CaSR function may be dependent on the cells and tissues in which it is expressed. For example, CaSR is also involved in regulating osteoclast differentiation [28] and promotes apoptosis in a variety of cell type [29, 30]. In fibroblasts, however, CaSR regulates cell survival and is anti-apoptotic [31].…”

Section: Discussionmentioning

confidence: 99%

Calcium and calcium sensing receptor modulates the expression of thymidylate synthase, NAD(P)H:quinone oxidoreductase 1 and survivin in human colon carcinoma cells: Promotion of cytotoxic response to mitomycin C and fluorouracil

Varani

Chakrabarty

2008

Molecular Carcinogenesis

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Ca 2+ and the cell-surface calcium sensing receptor (CaSR) constitute a novel and robust ligand/ receptor system in regulating the proliferation and differentiation of colonic epithelial cells. Here we show that activation of CaSR by extracellular Ca 2+ (or CaSR agonists) enhanced the sensitivity of human colon carcinoma cells to mitomycin C (MMC) and fluorouracil (5-FU). Activation of CaSR up-regulated the expression of MMC activating enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO-1) and down-regulated the expression of 5-FU target, thymidylate synthase (TS) and the anti-apoptotic protein survivin. Cells that were resistant to drugs expressed little or no CaSR but abundant amount of survivin. Disruption of CaSR expression by shRNA targeting the CaSR abrogated these modulating effects of CaSR activation on the expression of NQO1, TS, survivin and cytotoxic response to drugs. It is concluded that activation of CaSR can enhance colon cancer cell sensitivity to MMC and 5-FU and can modulate the expression of molecules involved in the cellular responses to these cytotoxic drugs.

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“…Ceramides, a SPL precursor that is formed from the direct condensation of VLCFAs with a long chain base by ceramide synthase, are reported to play role in apoptosis, growth arrest, endocytosis and stress response [157][158][159][160][161][162]. …”

Section: Ceramide and Sphingolipid Synthesismentioning

confidence: 99%

Characterization of Enzymes Involved in Fatty Acid Elongation

Paul¹

2007

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Role of ceramide in Ca2+-sensing receptor-induced apoptosis

Cited by 17 publications

References 49 publications

Roles of cPLA2α and arachidonic acid in cancer

Roles of cPLA2α and arachidonic acid in cancer

Calcium and calcium sensing receptor modulates the expression of thymidylate synthase, NAD(P)H:quinone oxidoreductase 1 and survivin in human colon carcinoma cells: Promotion of cytotoxic response to mitomycin C and fluorouracil

Characterization of Enzymes Involved in Fatty Acid Elongation

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