Increased liver AGEs induce hepatic injury mediated through an OST48 pathway

A Zhuang; FY Yap; C Bruce; C Leung; MR Plan; MA Sullivan; C Herath; D McCarthy; KC Sourris; P Kantharidis; MT Coughlan; MA Febbraio; MP Hodson; MJ Watt; P Angus; BL Schulz; JM Forbes

Journal article

Increased liver AGEs induce hepatic injury mediated through an OST48 pathway

A Zhuang, FY Yap, C Bruce, C Leung, MR Plan, MA Sullivan, C Herath, D McCarthy, KC Sourris, P Kantharidis, MT Coughlan, MA Febbraio, MP Hodson, MJ Watt, P Angus, BL Schulz, JM Forbes

Scientific Reports | NATURE PORTFOLIO | Published : 2017

DOI: 10.1038/s41598-017-12548-4

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Abstract

The protein oligosaccharyltransferase-48 (OST48) is integral to protein N-glycosylation in the endoplasmic reticulum (ER) but is also postulated to act as a membrane localised clearance receptor for advanced glycation end-products (AGE). Hepatic ER stress and AGE accumulation are each implicated in liver injury. Hence the objective of this study was to increase the expression of OST48 and examine the effects on hepatic function and structure. Groups of 8 week old male mice (n = 10-12/group) over-expressing the gene for OST48, dolichyl-diphosphooligosaccharide-protein glycosyltransferase (DDOST+/-), were followed for 24 weeks, while randomised to diets either low or high in AGE content. By we..

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University of Melbourne Researchers

Aowen Zhuang Author

Chris Leung Author

Chandana Herath Author

Matt Watt Author

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Awarded by National Health and Medical Research Council

Funding Acknowledgements

The authors would like to acknowledge Maryann Arnstein, Anna Gasser and Vicki Bonke at Baker IDI Heart and Diabetes Institute, Melbourne Australia, for technical assistance. JMF is supported by a Senior Research Fellowship (APP1004503; 1102935) from the National Health and Medical Research Council of Australia (NH&MRC). BLS is supported by a Career Development Fellowship (APP1087975) from the NH&MRC. AZ received a scholarship from Kidney Health Australia (SCH17; 141516) and the Mater Research Foundation. FYTY was funded by scholarship from the NH&MRC. MTF received support as an ANZSN/Roche Career Development Fellow. MJW is supported by a Senior Research Fellowship from the NHMRC (GNT1077703). The Metabolomics Australia Queensland Node is funded through Bioplatforms Australia/NCRIS. This research was supported by the NH&MRC and the Mater Foundation, which had no role in the study design, data collection and analysis, decision to publish, or preparation or the manuscript.