The known unknowns of apolipoprotein glycosylation in health and disease

Subramanian, Sabarinath Peruvemba; Gundry, Rebekah L.

doi:10.1016/j.isci.2022.105031

Cited by 10 publications

(11 citation statements)

References 125 publications

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“…38 In the Golgi, it has been proposed that VLDL undergoes additional lipidation, but the data are conflicting 129,131,132 and further research is warranted. VLDL undergoes extensive glycosylation of apoB (for review, see the study by Subramanian and Gundry 119 ), but there are almost no studies how apoB/VLDL is transported across the Golgi, with little if anything known about the steps needed for VLDL to exit the Golgi, how it is transported to the cell membrane, or how VLDL is secreted from the cell. 137 In vivo studies of VLDL secretion have not added to this paucity of knowledge in this component of cellular VLDL biology.…”

Section: Discussionmentioning

confidence: 99%

“…Three decades ago, a series of studies showed that posttranslational modifications of apoB/VLDL occur in the Golgi. [119][120][121] In a recent review on the glycosylation of apolipoproteins, it was reported that apoB100 has 19 potential N-glycosylation sites, of which 17 sites are glycosylated in regions including the MTP and lipid-binding domains. 119 Using McArdle RH-7777 cells, it has been shown that defective N-glycosylation within apoB-37 can affect the secretion of VLDL.…”

Section: Golgi and Secretionmentioning

confidence: 99%

“…[119][120][121] In a recent review on the glycosylation of apolipoproteins, it was reported that apoB100 has 19 potential N-glycosylation sites, of which 17 sites are glycosylated in regions including the MTP and lipid-binding domains. 119 Using McArdle RH-7777 cells, it has been shown that defective N-glycosylation within apoB-37 can affect the secretion of VLDL. 122 Reduced apoB100 secretion can also be due to enhanced proteasomal degradation as a result of glucosamine-induced N-linked glycosylation defects in McArdle RH-7777 cells.…”

Section: Golgi and Secretionmentioning

confidence: 99%

See 2 more Smart Citations

VLDL Biogenesis and Secretion: It Takes a Village

van Zwol,

van de Sluis,

Ginsberg

et al. 2024

Circulation Research

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The production and secretion of VLDLs (very-low-density lipoproteins) by hepatocytes has a direct impact on liver fat content, as well as the concentrations of cholesterol and triglycerides in the circulation and thus affects both liver and cardiovascular health, respectively. Importantly, insulin resistance, excess caloric intake, and lack of physical activity are associated with overproduction of VLDL, hepatic steatosis, and increased plasma levels of atherogenic lipoproteins. Cholesterol and triglycerides in remnant particles generated by VLDL lipolysis are risk factors for atherosclerotic cardiovascular disease and have garnered increasing attention over the last few decades. Presently, however, increased risk of atherosclerosis is not the only concern when considering today’s cardiometabolic patients, as they often also experience hepatic steatosis, a prevalent disorder that can progress to steatohepatitis and cirrhosis. This duality of metabolic risk highlights the importance of understanding the molecular regulation of the biogenesis of VLDL, the lipoprotein that transports triglycerides and cholesterol out of the liver. Fortunately, there has been a resurgence of interest in the intracellular assembly, trafficking, degradation, and secretion of VLDL by hepatocytes, which has led to many exciting new molecular insights that are the topic of this review. Increasing our understanding of the biology of this pathway will aid to the identification of novel therapeutic targets to improve both the cardiovascular and the hepatic health of cardiometabolic patients. This review focuses, for the first time, on this duality.

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Section: Discussionmentioning

confidence: 99%

Section: Golgi and Secretionmentioning

confidence: 99%

Section: Golgi and Secretionmentioning

confidence: 99%

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VLDL Biogenesis and Secretion: It Takes a Village

van Zwol,

van de Sluis,

Ginsberg

et al. 2024

Circulation Research

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“…80 Often one can find various combinations or all forms of aberrant glycosylation on specific proteins important for proper cell growth and death. 81 Recently, there has been a rapid development of technologies to analyze glycosylation. The enzymes needed for glycosylation are ubiquitous and often essential across organ systems.…”

Section: Glycosylation In Diseasementioning

confidence: 99%

Mass Spectrometry-Based Glycoproteomic Workflows for Cancer Biomarker Discovery

Doud

Yeh

2023

Technol Cancer Res Treat

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Glycosylation has a clear role in cancer initiation and progression, with numerous studies identifying distinct glycan features or specific glycoproteoforms associated with cancer. Common findings include that aggressive cancers tend to have higher expression levels of enzymes that regulate glycosylation as well as glycoproteins with greater levels of complexity, increased branching, and enhanced chain length1. Research in cancer glycoproteomics over the last 50-plus years has mainly focused on technology development used to observe global changes in glycosylation. Efforts have also been made to connect glycans to their protein carriers as well as to delineate the role of these modifications in intracellular signaling and subsequent cell function. This review discusses currently available techniques utilizing mass spectrometry-based technologies used to study glycosylation and highlights areas for future advancement.

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“…One study provides evidence that VLDL in wild-type mice docks to ERGIC and the cis-Golgi 33 . VLDL trafficking through the Golgi is required to explain the extensive glycosylation of apoB (for review see 110 ) and it has further been suggested that VLDL undergoes additional lipidation (see review 111 ). However, there are almost no studies how apoB/VLDL finds its way through the Golgi.…”

Section: Golgi and Hepatic Secretionmentioning

confidence: 99%

VLDL Biogenesis and Secretion: It Takes a Village

Zwol¹,

Sluis²,

Ginsberg³

et al. 2023

Preprint

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The production and secretion of very-low density lipoproteins (VLDL) by hepatocytes has a direct impact on liver fat content as well as the concentration of cholesterol and triglycerides in the circulation and thus affects liver and cardiovascular health, respectively. Importantly, excess caloric intake and lack of physical activity are associated with overproduction of VLDL, hepatic steatosis, and increased levels of atherogenic lipoproteins. Cholesterol as well as triglycerides in remnant particles after VLDL lipolysis are risk factors for atherosclerotic cardiovascular disease (ASCVD) and have garnered increasing attention over the last few decades. To date, however, increased risk of ASCVD is not the only concern when considering today’s cardiometabolic patients, as they often also suffer from hepatic steatosis. This notion highlights the importance of understanding the molecular regulation of VLDL biogenesis. Fortunately, there has been a resurgence of interest in the intracellular assembly, trafficking, degradation, and secretion of VLDL by hepatocytes, that has led to many exciting new molecular insights, the topic of this review. We think that increasing our understanding of the biology of this pathway will help improve the health of the cardiometabolic patient in the long term.

show abstract

The known unknowns of apolipoprotein glycosylation in health and disease

Cited by 10 publications

References 125 publications

VLDL Biogenesis and Secretion: It Takes a Village

VLDL Biogenesis and Secretion: It Takes a Village

Mass Spectrometry-Based Glycoproteomic Workflows for Cancer Biomarker Discovery

VLDL Biogenesis and Secretion: It Takes a Village

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