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Kristine Glunde - One of the best experts on this subject based on the ideXlab platform.
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Focus on the Glycerophosphocholine pathway in choline phospholipid metabolism of cancer.
NMR in Biomedicine, 2019Co-Authors: Kanchan Sonkar, Menglin Cheng, Vinay Ayyappan, Caitlin M. Tressler, Oluwatobi Adelaja, Ruoqing Cai, Kristine GlundeAbstract:Activated choline metabolism is a hallmark of carcinogenesis and tumor progression, which leads to elevated levels of phosphocholine and Glycerophosphocholine in all types of cancer tested so far. Magnetic resonance spectroscopy applications have played a key role in detecting these elevated choline phospholipid metabolites. To date, the majority of cancer-related studies have focused on phosphocholine and the Kennedy pathway, which constitutes the biosynthesis pathway for membrane phosphatidylcholine. Fewer and more recent studies have reported on the importance of Glycerophosphocholine in cancer. In this review article, we summarize the recent literature on Glycerophosphocholine metabolism with respect to its cancer biology and its detection by magnetic resonance spectroscopy applications.
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silencing of the Glycerophosphocholine phosphodiesterase gdpd5 alters the phospholipid metabolite profile in a breast cancer model in vivo as monitored by 31p magnetic resonance spectroscopy
NMR in Biomedicine, 2014Co-Authors: Jannie P. Wijnen, Maria D. Cao, Mailin Döpkens, Balaji Krishnamachary, Zaver M. Bhujwalla, Tiffany R. Greenwood, Lu Jiang, Menglin Cheng, Dennis W.j. Klomp, Kristine GlundeAbstract:Abnormal choline phospholipid metabolism is an emerging hallmark of cancer, which is implicated in carcinogenesis and tumor progression. The malignant metabolic phenotype is characterized by high levels of phosphocholine (PC) and relatively low levels of Glycerophosphocholine (GPC) in aggressive breast cancer cells. Phosphorus Magnetic Resonance Spectroscopy (31P MRS) is able to noninvasively detect these water-soluble metabolites of choline as well as ethanolamine phospholipid metabolism. Here we have investigated the effects of stably silencing glycerophosphoester diesterase domain containing 5 (GDPD5), which is an enzyme with Glycerophosphocholine phosphodiesterase activity, in MDA-MB-231 breast cancer cells and orthotopic tumor xenografts. Tumors in which GDPD5 was stably silenced with GDPD5-specific shRNA contained increased levels of GPC and phosphoethanolamine (PE) compared to control tumors.
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Silencing of the Glycerophosphocholine phosphodiesterase GDPD5 alters the phospholipid metabolite profile in a breast cancer model in vivo as monitored by 31P MRS
NMR in Biomedicine, 2014Co-Authors: Jannie P. Wijnen, Maria D. Cao, Mailin Döpkens, Balaji Krishnamachary, Zaver M. Bhujwalla, Tiffany R. Greenwood, Lu Jiang, Menglin Cheng, Dennis W.j. Klomp, Kristine GlundeAbstract:Abnormal choline phospholipid metabolism is an emerging hallmark of cancer, which is implicated in carcinogenesis and tumor progression. The malignant metabolic phenotype is characterized by high levels of phosphocholine (PC) and relatively low levels of Glycerophosphocholine (GPC) in aggressive breast cancer cells. Phosphorus (31P) MRS is able to non-invasively detect these water-soluble metabolites of choline as well as ethanolamine phospholipid metabolism. Here we have investigated the effects of stably silencing glycerophosphoester diesterase domain containing 5 (GDPD5), which is an enzyme with Glycerophosphocholine phosphodiesterase activity, in MDA-MB-231 breast cancer cells and orthotopic tumor xenografts. Tumors in which GDPD5 was stably silenced with GDPD5-specific shRNA contained increased levels of GPC and phosphoethanolamine (PE) compared with control tumors. Copyright © 2014 John Wiley & Sons, Ltd.
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Glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) expression correlates with malignant choline phospholipid metabolite profiles in human breast cancer.
NMR in Biomedicine, 2012Co-Authors: Maria D. Cao, Ingrid S. Gribbestad, Mailin Döpkens, Balaji Krishnamachary, Farhad Vesuna, Mayur Gadiya, Per Eystein Lønning, Zaver M. Bhujwalla, Kristine GlundeAbstract:Altered choline phospholipid metabolism is a hallmark of cancer, leading to malignant choline metabolite profiles consisting of low Glycerophosphocholine (GPC) and high phosphocholine (PC) in human breast cancers. Glycerophosphocholine phosphodiesterase (GPC-PDE) catalyzes the degradation of GPC to free choline and glycerol-3-phosphate. The gene(s) encoding for the GPC-PDE(s) responsible for GPC degradation in breast cancers have not yet been identified. Here, we demonstrate for the first time that the GPC-PDE encoded by glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) is associated with breast cancer malignancy. Two human breast cancer cell lines (n=8 and n=10) and primary human breast tumor samples (n=19) were studied with combined MRS and quantitative reverse transcription-polymerase chain reaction to investigate several isoforms of GDPD expression with respect to choline phospholipid metabolite levels. Of the five GDPDs tested, GDPD5 was found to be significantly overexpressed in highly malignant estrogen receptor negative (ER – ) compared with weakly malignant estrogen receptor positive (ER + ) human breast cancer cells (p=0.027) and breast tumors from patients (p=0.015). GDPD5 showed significantly positive correlations with PC (p
Zaver M. Bhujwalla - One of the best experts on this subject based on the ideXlab platform.
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silencing of the Glycerophosphocholine phosphodiesterase gdpd5 alters the phospholipid metabolite profile in a breast cancer model in vivo as monitored by 31p magnetic resonance spectroscopy
NMR in Biomedicine, 2014Co-Authors: Jannie P. Wijnen, Maria D. Cao, Mailin Döpkens, Balaji Krishnamachary, Zaver M. Bhujwalla, Tiffany R. Greenwood, Lu Jiang, Menglin Cheng, Dennis W.j. Klomp, Kristine GlundeAbstract:Abnormal choline phospholipid metabolism is an emerging hallmark of cancer, which is implicated in carcinogenesis and tumor progression. The malignant metabolic phenotype is characterized by high levels of phosphocholine (PC) and relatively low levels of Glycerophosphocholine (GPC) in aggressive breast cancer cells. Phosphorus Magnetic Resonance Spectroscopy (31P MRS) is able to noninvasively detect these water-soluble metabolites of choline as well as ethanolamine phospholipid metabolism. Here we have investigated the effects of stably silencing glycerophosphoester diesterase domain containing 5 (GDPD5), which is an enzyme with Glycerophosphocholine phosphodiesterase activity, in MDA-MB-231 breast cancer cells and orthotopic tumor xenografts. Tumors in which GDPD5 was stably silenced with GDPD5-specific shRNA contained increased levels of GPC and phosphoethanolamine (PE) compared to control tumors.
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Silencing of the Glycerophosphocholine phosphodiesterase GDPD5 alters the phospholipid metabolite profile in a breast cancer model in vivo as monitored by 31P MRS
NMR in Biomedicine, 2014Co-Authors: Jannie P. Wijnen, Maria D. Cao, Mailin Döpkens, Balaji Krishnamachary, Zaver M. Bhujwalla, Tiffany R. Greenwood, Lu Jiang, Menglin Cheng, Dennis W.j. Klomp, Kristine GlundeAbstract:Abnormal choline phospholipid metabolism is an emerging hallmark of cancer, which is implicated in carcinogenesis and tumor progression. The malignant metabolic phenotype is characterized by high levels of phosphocholine (PC) and relatively low levels of Glycerophosphocholine (GPC) in aggressive breast cancer cells. Phosphorus (31P) MRS is able to non-invasively detect these water-soluble metabolites of choline as well as ethanolamine phospholipid metabolism. Here we have investigated the effects of stably silencing glycerophosphoester diesterase domain containing 5 (GDPD5), which is an enzyme with Glycerophosphocholine phosphodiesterase activity, in MDA-MB-231 breast cancer cells and orthotopic tumor xenografts. Tumors in which GDPD5 was stably silenced with GDPD5-specific shRNA contained increased levels of GPC and phosphoethanolamine (PE) compared with control tumors. Copyright © 2014 John Wiley & Sons, Ltd.
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Glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) expression correlates with malignant choline phospholipid metabolite profiles in human breast cancer.
NMR in Biomedicine, 2012Co-Authors: Maria D. Cao, Ingrid S. Gribbestad, Mailin Döpkens, Balaji Krishnamachary, Farhad Vesuna, Mayur Gadiya, Per Eystein Lønning, Zaver M. Bhujwalla, Kristine GlundeAbstract:Altered choline phospholipid metabolism is a hallmark of cancer, leading to malignant choline metabolite profiles consisting of low Glycerophosphocholine (GPC) and high phosphocholine (PC) in human breast cancers. Glycerophosphocholine phosphodiesterase (GPC-PDE) catalyzes the degradation of GPC to free choline and glycerol-3-phosphate. The gene(s) encoding for the GPC-PDE(s) responsible for GPC degradation in breast cancers have not yet been identified. Here, we demonstrate for the first time that the GPC-PDE encoded by glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) is associated with breast cancer malignancy. Two human breast cancer cell lines (n=8 and n=10) and primary human breast tumor samples (n=19) were studied with combined MRS and quantitative reverse transcription-polymerase chain reaction to investigate several isoforms of GDPD expression with respect to choline phospholipid metabolite levels. Of the five GDPDs tested, GDPD5 was found to be significantly overexpressed in highly malignant estrogen receptor negative (ER – ) compared with weakly malignant estrogen receptor positive (ER + ) human breast cancer cells (p=0.027) and breast tumors from patients (p=0.015). GDPD5 showed significantly positive correlations with PC (p
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malignant transformation alters membrane choline phospholipid metabolism of human mammary epithelial cells
Cancer Research, 1999Co-Authors: Eric O Aboagye, Zaver M. BhujwallaAbstract:Transduction of mitogenic signals in cells can be mediated by molecules derived from the synthesis and breakdown of the major membrane phospholipid, phosphotidylcholine. Studies were performed on human mammary epithelial cells in culture to understand the impact of malignant transformation and progression on membrane phospholipid metabolism. In the model system used here, phosphocholine levels and total choline-containing phospholipid metabolite levels increased with progression from normal to immortalized to oncogene-transformed to tumor-derived cells. These changes occurred independently of cell doubling time. A “Glycerophosphocholine to phosphocholine switch” was apparent with immortalization. This alteration in phenotype of increased phosphocholine relative to Glycerophosphocholine was observed in oncogene-transformed and for all human breast tumor cell lines analyzed. The results demonstrate that progression of human mammary epithelial cells from normal to malignant phenotype is associated with altered membrane choline phospholipid metabolism.
D E Sok - One of the best experts on this subject based on the ideXlab platform.
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Characterization of a Zn(2+)-requiring Glycerophosphocholine cholinephosphodiesterase possessing p-nitrophenylphosphocholine phosphodiesterase activity.
Biochemical Journal, 1992Co-Authors: D E Sok, Mee Ree KimAbstract:p-Nitrophenylphosphocholine phosphodiesterase activity was purified 5000-fold from mouse brain by treatment of membranes with Bacillus cereus phospholipase C preparation and sequential chromatographies on concanavalin A-Sepharose and CM-Sephadex columns. The phosphodiesterase (Zn(2+)-requiring) showed Km and Vmax. values of 5.5 microM and 4.2 mumol/min per mg respectively in the hydrolysis of p-nitrophenylphosphocholine, and possessed an optimum pH of 10.5 and a molecular mass of approx. 74 kDa. The purified enzyme was found to convert Glycerophosphocholine into glycerol and phosphocholine, with Km and Vmax. of 48 microM and 5 mumol/min per mg respectively. In the hydrolysis of Glycerophosphocholine the enzyme also exhibited a Zn2+ requirement and optimal pH at 10.5. Additionally, the p-nitrophenylphosphocholine phosphodiesterase activity was competitively inhibited by Glycerophosphocholine, with a Ki value of 50 microM. These observations, together with chromatographic behaviour and heat-denaturation analyses, indicate that both p-nitrophenylphosphocholine phosphodiesterase and Glycerophosphocholine cholinephosphodiesterase activities reside in the same protein.
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Selective inhibition of Zn2+-Glycerophosphocholine cholinephosphodiesterase by tellurium tetrachloride
Biochemical Journal, 1992Co-Authors: D E Sok, Mee Ree KimAbstract:A Zn(2+)-Glycerophosphocholine cholinephosphodiesterase (EC 3.1.4.38) purified from mouse brain was found to be reversibly inhibited by tellurium tetrachloride. This effect was characterized by a competitive pattern of inhibition, with apparent Ki values of 0.7 microM and 1.5 microM for the hydrolysis of p-nitrophenylphosphocholine and Glycerophosphocholine respectively. Interestingly, the inhibitory effect of tellurium tetrachloride was found to be greatly potentiated by tetramethylammonium salt, indicative of a synergistic interaction between the two compounds. Additionally, it was observed that the effect of tellurium tetrachloride was not affected by a number of other metal ions, and was more pronounced at neutral pH, suggesting that the inhibitory role of the tellurium tetrachloride may be of importance under physiological conditions. Thus Zn(2+)-Glycerophosphocholine cholinephosphodiesterase is proposed to be one of the target enzymes which is susceptible to the inhibitory effect of tellurium tetrachloride.
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Selective inhibition of Zn(2+)-Glycerophosphocholine cholinephosphodiesterase by tellurium tetrachloride.
The Biochemical journal, 1992Co-Authors: D E Sok, M R KimAbstract:A Zn(2+)-Glycerophosphocholine cholinephosphodiesterase (EC 3.1.4.38) purified from mouse brain was found to be reversibly inhibited by tellurium tetrachloride. This effect was characterized by a competitive pattern of inhibition, with apparent Ki values of 0.7 microM and 1.5 microM for the hydrolysis of p-nitrophenylphosphocholine and Glycerophosphocholine respectively. Interestingly, the inhibitory effect of tellurium tetrachloride was found to be greatly potentiated by tetramethylammonium salt, indicative of a synergistic interaction between the two compounds. Additionally, it was observed that the effect of tellurium tetrachloride was not affected by a number of other metal ions, and was more pronounced at neutral pH, suggesting that the inhibitory role of the tellurium tetrachloride may be of importance under physiological conditions. Thus Zn(2+)-Glycerophosphocholine cholinephosphodiesterase is proposed to be one of the target enzymes which is susceptible to the inhibitory effect of tellurium tetrachloride.
Mee Ree Kim - One of the best experts on this subject based on the ideXlab platform.
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Interaction of Divalent Metal Ions with Zn2+-Glycerophosphocholine Cholinephosphodiesterase from Ox Brain
Neurochemical research, 1997Co-Authors: Kun Jong Lee, Mee Ree Kim, Yun-bae Kim, Pyung-keun Myung, Dai-eun SokAbstract:The effect of divalent metal ions on the activity of Glycerophosphocholine cholinephosphodiesterse from ox brain was examined. Zn2+- and Co2+-Glycerophosphocholine cholinephosphodiesterases were prepared from the exposure of apoenzyme to Zn2+ and Co2+, respectively, and the properties of two metallo-phosphodiesterases were compared to those of native phosphodiesterase. Although two metallo-enzymes were similar in expressing Km value, optimum pH or sensitivity to Cu2+, they differed in the susceptibility to the inhibition by thiocholine or tellurite; while Co2+-phosphodiesterase was more sensitive to tellurites, Zn2+-phosphodiesterase was more susceptible to inhibition by thiocholine. In addition, Zn2+-phosphodiesterase was more thermo-stable than Co2+ enzyme. Separately, when properties of native phosphodiesterase were compared to those of each metallo-phosphodiesterase, native phosphodiesterase was found to be quite similar to Zn2+-phosphodiesterase in many respects. Even in thermo-stability, native enzyme resembled Zn2+-phosphodiesterase rather than Co2+-enzyme. Consistent with this, the stability of native phosphodiesterase was maintained in the presence of Zn2+, but not Co2+. Mn2+ was also as effective as Zn2+ in the stabilization of the enzyme. Noteworthy, the native enzyme was found to be inhibited competitively by Cu2+ with a Ki value of 20 μM, and its inhibitory action was antagonized effectively by Zn2+ or Co2+. Also, choline, another competitive inhibitor of the enzyme, appeared to antagonize the inhibitory action of Cu2+. Taken together, it is suggested that there may be multiple binding sites for divalent metal ions in the molecule of Glycerophosphocholine cholinephosphodiesterase.
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Characterization of a Zn(2+)-requiring Glycerophosphocholine cholinephosphodiesterase possessing p-nitrophenylphosphocholine phosphodiesterase activity.
Biochemical Journal, 1992Co-Authors: D E Sok, Mee Ree KimAbstract:p-Nitrophenylphosphocholine phosphodiesterase activity was purified 5000-fold from mouse brain by treatment of membranes with Bacillus cereus phospholipase C preparation and sequential chromatographies on concanavalin A-Sepharose and CM-Sephadex columns. The phosphodiesterase (Zn(2+)-requiring) showed Km and Vmax. values of 5.5 microM and 4.2 mumol/min per mg respectively in the hydrolysis of p-nitrophenylphosphocholine, and possessed an optimum pH of 10.5 and a molecular mass of approx. 74 kDa. The purified enzyme was found to convert Glycerophosphocholine into glycerol and phosphocholine, with Km and Vmax. of 48 microM and 5 mumol/min per mg respectively. In the hydrolysis of Glycerophosphocholine the enzyme also exhibited a Zn2+ requirement and optimal pH at 10.5. Additionally, the p-nitrophenylphosphocholine phosphodiesterase activity was competitively inhibited by Glycerophosphocholine, with a Ki value of 50 microM. These observations, together with chromatographic behaviour and heat-denaturation analyses, indicate that both p-nitrophenylphosphocholine phosphodiesterase and Glycerophosphocholine cholinephosphodiesterase activities reside in the same protein.
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Selective inhibition of Zn2+-Glycerophosphocholine cholinephosphodiesterase by tellurium tetrachloride
Biochemical Journal, 1992Co-Authors: D E Sok, Mee Ree KimAbstract:A Zn(2+)-Glycerophosphocholine cholinephosphodiesterase (EC 3.1.4.38) purified from mouse brain was found to be reversibly inhibited by tellurium tetrachloride. This effect was characterized by a competitive pattern of inhibition, with apparent Ki values of 0.7 microM and 1.5 microM for the hydrolysis of p-nitrophenylphosphocholine and Glycerophosphocholine respectively. Interestingly, the inhibitory effect of tellurium tetrachloride was found to be greatly potentiated by tetramethylammonium salt, indicative of a synergistic interaction between the two compounds. Additionally, it was observed that the effect of tellurium tetrachloride was not affected by a number of other metal ions, and was more pronounced at neutral pH, suggesting that the inhibitory role of the tellurium tetrachloride may be of importance under physiological conditions. Thus Zn(2+)-Glycerophosphocholine cholinephosphodiesterase is proposed to be one of the target enzymes which is susceptible to the inhibitory effect of tellurium tetrachloride.
Maria D. Cao - One of the best experts on this subject based on the ideXlab platform.
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silencing of the Glycerophosphocholine phosphodiesterase gdpd5 alters the phospholipid metabolite profile in a breast cancer model in vivo as monitored by 31p magnetic resonance spectroscopy
NMR in Biomedicine, 2014Co-Authors: Jannie P. Wijnen, Maria D. Cao, Mailin Döpkens, Balaji Krishnamachary, Zaver M. Bhujwalla, Tiffany R. Greenwood, Lu Jiang, Menglin Cheng, Dennis W.j. Klomp, Kristine GlundeAbstract:Abnormal choline phospholipid metabolism is an emerging hallmark of cancer, which is implicated in carcinogenesis and tumor progression. The malignant metabolic phenotype is characterized by high levels of phosphocholine (PC) and relatively low levels of Glycerophosphocholine (GPC) in aggressive breast cancer cells. Phosphorus Magnetic Resonance Spectroscopy (31P MRS) is able to noninvasively detect these water-soluble metabolites of choline as well as ethanolamine phospholipid metabolism. Here we have investigated the effects of stably silencing glycerophosphoester diesterase domain containing 5 (GDPD5), which is an enzyme with Glycerophosphocholine phosphodiesterase activity, in MDA-MB-231 breast cancer cells and orthotopic tumor xenografts. Tumors in which GDPD5 was stably silenced with GDPD5-specific shRNA contained increased levels of GPC and phosphoethanolamine (PE) compared to control tumors.
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Silencing of the Glycerophosphocholine phosphodiesterase GDPD5 alters the phospholipid metabolite profile in a breast cancer model in vivo as monitored by 31P MRS
NMR in Biomedicine, 2014Co-Authors: Jannie P. Wijnen, Maria D. Cao, Mailin Döpkens, Balaji Krishnamachary, Zaver M. Bhujwalla, Tiffany R. Greenwood, Lu Jiang, Menglin Cheng, Dennis W.j. Klomp, Kristine GlundeAbstract:Abnormal choline phospholipid metabolism is an emerging hallmark of cancer, which is implicated in carcinogenesis and tumor progression. The malignant metabolic phenotype is characterized by high levels of phosphocholine (PC) and relatively low levels of Glycerophosphocholine (GPC) in aggressive breast cancer cells. Phosphorus (31P) MRS is able to non-invasively detect these water-soluble metabolites of choline as well as ethanolamine phospholipid metabolism. Here we have investigated the effects of stably silencing glycerophosphoester diesterase domain containing 5 (GDPD5), which is an enzyme with Glycerophosphocholine phosphodiesterase activity, in MDA-MB-231 breast cancer cells and orthotopic tumor xenografts. Tumors in which GDPD5 was stably silenced with GDPD5-specific shRNA contained increased levels of GPC and phosphoethanolamine (PE) compared with control tumors. Copyright © 2014 John Wiley & Sons, Ltd.
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Glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) expression correlates with malignant choline phospholipid metabolite profiles in human breast cancer.
NMR in Biomedicine, 2012Co-Authors: Maria D. Cao, Ingrid S. Gribbestad, Mailin Döpkens, Balaji Krishnamachary, Farhad Vesuna, Mayur Gadiya, Per Eystein Lønning, Zaver M. Bhujwalla, Kristine GlundeAbstract:Altered choline phospholipid metabolism is a hallmark of cancer, leading to malignant choline metabolite profiles consisting of low Glycerophosphocholine (GPC) and high phosphocholine (PC) in human breast cancers. Glycerophosphocholine phosphodiesterase (GPC-PDE) catalyzes the degradation of GPC to free choline and glycerol-3-phosphate. The gene(s) encoding for the GPC-PDE(s) responsible for GPC degradation in breast cancers have not yet been identified. Here, we demonstrate for the first time that the GPC-PDE encoded by glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) is associated with breast cancer malignancy. Two human breast cancer cell lines (n=8 and n=10) and primary human breast tumor samples (n=19) were studied with combined MRS and quantitative reverse transcription-polymerase chain reaction to investigate several isoforms of GDPD expression with respect to choline phospholipid metabolite levels. Of the five GDPDs tested, GDPD5 was found to be significantly overexpressed in highly malignant estrogen receptor negative (ER – ) compared with weakly malignant estrogen receptor positive (ER + ) human breast cancer cells (p=0.027) and breast tumors from patients (p=0.015). GDPD5 showed significantly positive correlations with PC (p