Phospholipase D2 mediates signaling by ATPase class I type 8B membrane 1

Chen, Fanglin; Ghosh, Anup K.; Shneider, Benjamin L.

doi:10.1194/jlr.m030304

Cited by 9 publications

(5 citation statements)

References 51 publications

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“…Although it is the major cancer of men in the Western world, surprisingly little is known about the expression and activity of PLD1 and PLD2 in PCa. In this first report on PLD isoforms in PCa, we have investigated PLD1 using a commercial anti-PLD1 antibody (sc-25512), which has been validated for western blotting (Disse et al , 2009; Scott et al , 2009; Chen et al , 2013) and which has also been used to detect PLD1 in cells by immunofluorescence (Disse et al , 2009; Han et al , 2011). We have not examined PLD2 expression in this work since, in agreement with Scott (Scott et al , 2009), we have found commercial anti-PLD2 antibodies to be unreliable.…”

Section: Discussionmentioning

confidence: 99%

Phospholipase D inhibitors reduce human prostate cancer cell proliferation and colony formation

et al. 2017

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Section: Discussionmentioning

confidence: 99%

Phospholipase D inhibitors reduce human prostate cancer cell proliferation and colony formation

et al. 2017

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“…Thus, it becomes evident that any mechanisms of halopemide-derived inhibitor other than direct inhibition of the PLD catalytic activity have not been identified. In the HepG2 cells, as well as in the primarily derived human hepatocytes silencing PLD2 by siPLD2 or by halopemide analog, FIPI, was associated with a significant reduction in atypical PKC ξ [ 68 ]. Moreover, it has been demonstrated that PA can activate PKC ξ / λ in the skeletal muscles [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

Modulation of Insulin Sensitivity of Hepatocytes by the Pharmacological Downregulation of Phospholipase D

Babenko

Kharchenko

2015

International Journal of Endocrinology

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Background. The role of phospholipase D (PLD) as a positive modulator of glucose uptake activation by insulin in muscle and adipose cells has been demonstrated. The role of PLD in the regulation of glucose metabolism by insulin in the primary hepatocytes has been determined in this study. Methods. For this purpose, we studied effects of inhibitors of PLD on glucose uptake and glycogen synthesis stimulation by insulin. To determine the PLD activity, the method based on determination of products of transphosphatidylation reaction, phosphatidylethanol or phosphatidylbutanol, was used. Results. Inhibition of PLD by a general antagonist (1-butanol) or specific inhibitor, halopemide, or N-hexanoylsphingosine, or by cellular ceramides accumulated in doxorubicin-treated hepatocytes decreased insulin-stimulated glucose metabolism. Doxorubicin-induced hepatocytes resistance to insulin action could be abolished by inhibition of ceramide production. Halopemide could nullify this effect. Addition of propranolol, as well as inhibitors of phosphatidylinositol 3-kinase (PI3-kinase) (wortmannin, LY294002) or suppressors of Akt phosphorylation/activity, luteolin-7-O-glucoside or apigenin-7-O-glucoside, to the culture media could block cell response to insulin action. Conclusion. PLD plays an important role in the insulin signaling in the hepatocytes. PLD is activated downstream of PI3-kinase and Akt and is highly sensitive to ceramide content in the liver cells.

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“…The third PFIC (and BRIC) gene, ATP8B1 , (ATPase class 8B member 1) encoding a phosphatidyl serine flippase (familial intrahepatic cholestasis 1, FIC1), has only been studied to a limited extent (with respect to sequencing) in ICP cohorts, and hence the role of genetic variation at this locus in ICP is not established 32 , 33 . A functional interdependence of this flippase with MDR3 in hepatocytes suggests that ATP8B1 remains a viable candidate for involvement in ICP susceptibility 34 , as does the link to ABCB11 function through FXR/PLD2 signalling 35 .…”

Section: Introductionmentioning

confidence: 99%

An expanded role for heterozygous mutations of ABCB4, ABCB11, ATP8B1, ABCC2 and TJP2 in intrahepatic cholestasis of pregnancy

Dixon

Sambrotta

Chambers

et al. 2017

Sci Rep

113

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Intrahepatic cholestasis of pregnancy (ICP) affects 1/140 UK pregnancies; with pruritus, hepatic impairment and elevated serum bile acids. Severe disease is complicated by spontaneous preterm delivery and stillbirth. Previous studies have reported mutations in hepatocellular transporters (ABCB4, ABCB11). High throughput sequencing in 147 patients was performed in the transporters ABCB4, ABCB11, ATP8B1, ABCC2 and tight junction protein 2 (TJP2). Twenty-six potentially damaging variants were identified with the following predicted protein changes: Twelve ABCB4 mutations - Arg47Gln, Met113Val, Glu161Gly, Thr175Ala, Glu528Glyfs*6, Arg590Gln, Ala601Ser, Glu884Ter, Gly722Ala, Tyr775Met (x2), Trp854Ter. Four potential ABCB11 mutations - Glu297Gly (x3) and a donor splice site mutation (intron 19). Five potential ATP8B1 mutations - Asn45Thr (x3), and two others, Glu114Gln and Lys203Glu. Two ABCC2 mutations - Glu1352Ala and a duplication (exons 24 and 25). Three potential mutations were identified in TJP2; Thr62Met (x2) and Thr626Ser. No patient harboured more than one mutation. All were heterozygous. An additional 545 cases were screened for the potential recurrent mutations of ATP8B1 (Asn45Thr) and TJP2 (Thr62Met) identifying three further occurrences of Asn45Thr. This study has expanded known mutations in ABCB4 and ABCB11 and identified roles in ICP for mutations in ATP8B1 and ABCC2. Possible novel mutations in TJP2 were also discovered.

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Phospholipase D2 mediates signaling by ATPase class I type 8B membrane 1

Cited by 9 publications

References 51 publications

Phospholipase D inhibitors reduce human prostate cancer cell proliferation and colony formation

Phospholipase D inhibitors reduce human prostate cancer cell proliferation and colony formation

Modulation of Insulin Sensitivity of Hepatocytes by the Pharmacological Downregulation of Phospholipase D

An expanded role for heterozygous mutations of ABCB4, ABCB11, ATP8B1, ABCC2 and TJP2 in intrahepatic cholestasis of pregnancy

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