The role of GPLD1 in chronic diseases

Zhou, Anni; Zhou, Zhifeng; Hui, Lam; Jia, Shaohui

doi:10.1002/jcp.31041

Cited by 5 publications

(3 citation statements)

References 70 publications

(80 reference statements)

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“…Additionally, its deletion correlates with reduced survival, induces hepatocyte autophagy, and cardiac hypertrophy . Glycosylphosphatidylinositol-specific phospholipase D (GPDL1) is highly produced by liver tissue and overexpressed in chronic NAFLD and other chronic liver injuries . Circulating GPLD1 is decreased variably in HCC dependent on etiology .…”

Section: Resultsmentioning

confidence: 99%

Differential Protease Specificity by Collagenase as a Novel Approach to Serum Proteomics That Includes Identification of Extracellular Matrix Proteins without Enrichment

Macdonald,

Clift,

Saunders

et al. 2024

J. Am. Soc. Mass Spectrom.

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Circulating extracellular matrix (ECM) proteins are serological biomarkers of interest due to their association with pathologies involving disease processes such as fibrosis and cancers. In this study, we investigate the potential for serum biomarker research using differential protease specificity (DPS), leveraging alternate protease specificity as a targeting mechanism to selectively digest circulating ECM protein serum proteins. A proof-of-concept study is presented using serum from patients with cirrhotic liver or hepatocellular carcinoma. The approach uses collagenase DPS for digestion of deglycosylated serum and liquidchromatography-trapped ion mobility-tandem mass spectrometry (LC-TIMS-MS/MS) to enhance the detection of ECM proteins in serum. It requires no sample enrichment and minimizes the albumin average precursor intensity readout to less than 1.2%. We further demonstrate the capabilities for using the method as a high-throughput matrix-assisted laser/desorption ionization mass spectrometry (MALDI-MS) assay coupled with reference library searching. A goal is to improve the depth and breadth of biofluid proteomics for noninvasive assays.

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Section: Resultsmentioning

confidence: 99%

Differential Protease Specificity by Collagenase as a Novel Approach to Serum Proteomics That Includes Identification of Extracellular Matrix Proteins without Enrichment

Macdonald,

Clift,

Saunders

et al. 2024

J. Am. Soc. Mass Spectrom.

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“…Gpld1 may perform different functions in different types of cells. Gpld1 has been showed to be predominantly expressed in the liver, with varying degrees of expression in other organs ( 38 ). Here, our study suggested that 3-HB administration up-regulates Gpld1 levels mainly in the liver but not in the spleens and lungs.…”

Section: Discussionmentioning

confidence: 99%

Exercise activates interferon response of the liver via Gpld1 to enhance antiviral innate immunity

Ren,

He,

Zhang

et al. 2024

Sci. Adv.

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Healthy behavioral patterns could modulate organ functions to enhance the body’s immunity. However, how exercise regulates antiviral innate immunity remains elusive. Here, we found that exercise promotes type I interferon (IFN-I) production in the liver and enhances IFN-I immune activity of the body. Despite the possibility that many exercise-induced factors could affect IFN-I production, we identified Gpld1 as a crucial molecule, and the liver as the major organ to promote IFN-I production after exercise. Exercise largely loses the efficiency to induce IFN-I in Gpld1 −/− mice. Further studies demonstrated that exercise-produced 3-hydroxybutanoic acid (3-HB) critically induces Gpld1 expression in the liver. Gpld1 blocks the PP2A-IRF3 interaction, thus enhancing IRF3 activation and IFN-I production, and eventually improving the body’s antiviral ability. This study reveals that exercise improves antiviral innate immunity by linking the liver metabolism to systemic IFN-I activity and uncovers an unknown function of liver cells in innate immunity.

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“…None have type II phospholipase activity but are reported to be involved in regulating the use of fatty acids as an energy supply. [45][46][47][48] Protection against oxidative stress defines resistance to cPLA2α inhibition.…”

Section: Gk420 Is a Potent Inhibitor Of Cpla2α In Cellular Assaysmentioning

confidence: 99%

Next Generation Thiazolyl Ketone Inhibitors of Cytosolic Phospholipase A2 α: from Synthesis to Chemotherapeutic Mechanism of Action

Johansen,

Ashcroft,

Bourmpoula

et al. 2023

Preprint

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Eicosanoids regulate the pathologies of inflammation and carcinogenesis and limiting their production by inhibiting group IVA cytosolic phospholipase A2 (cPLA2α) is a potential approach to cancer treatment. Here we report the synthesis of a new generation of thiazolyl ketone inhibitors of cPLA2α starting from compound GK470 (AVX235), and the discovery of a more potent and selective lead, GK420 (AVX420), with significant chemotherapeutic properties. A cancer cell line screen revealed the selective growth inhibitory effects of AVX420 in acute leukemias, uncovering a novel function of cPLA2α to promote cancer cell survival during oxidative stress by epigenetic control of tumour suppressor gene transcription. Moreover, we showed that in sensitive cells, AVX420 increased intracellular reactive oxygen species (ROS) and instigated a transcriptional response resulting in cell death. Our study suggests AVX420 has the potential to treat acute leukemias, and other cancers with specific adaptations to a high ROS burden.

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The role of GPLD1 in chronic diseases

Cited by 5 publications

References 70 publications

Differential Protease Specificity by Collagenase as a Novel Approach to Serum Proteomics That Includes Identification of Extracellular Matrix Proteins without Enrichment

Differential Protease Specificity by Collagenase as a Novel Approach to Serum Proteomics That Includes Identification of Extracellular Matrix Proteins without Enrichment

Exercise activates interferon response of the liver via Gpld1 to enhance antiviral innate immunity

Next Generation Thiazolyl Ketone Inhibitors of Cytosolic Phospholipase A2 α: from Synthesis to Chemotherapeutic Mechanism of Action

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