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Knockout of the rad...
Knockout of the radical scavenger α1-microglobulin in mice results in defective bikunin synthesis, endoplasmic reticulum stress and increased body weight
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- Bergwik, Jesper (författare)
- Lund University,Lunds universitet,Antioxidationsmedicin,Forskargrupper vid Lunds universitet,Antioxidation medicine,Lund University Research Groups
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- Kristiansson, Amanda (författare)
- Lund University,Lunds universitet,Antioxidationsmedicin,Forskargrupper vid Lunds universitet,Antioxidation medicine,Lund University Research Groups
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- Welinder, Charlotte (författare)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Göransson, Olga (författare)
- Lund University,Lunds universitet,Proteinfosforylering,Forskargrupper vid Lunds universitet,Protein Phosphorylation,Lund University Research Groups
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- Hansson, Stefan R. (författare)
- Lund University,Lunds universitet,Obstetrik och gynekologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Obstetrics and Gynaecology (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Gram, Magnus (författare)
- Lund University,Lunds universitet,Antioxidationsmedicin,Forskargrupper vid Lunds universitet,Sjukdomsorsakande oxidation,Antioxidation medicine,Lund University Research Groups,Redox Medicine
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- Erlandsson, Lena (författare)
- Lund University,Lunds universitet,Obstetrik och gynekologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Obstetrics and Gynaecology (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Åkerström, Bo (författare)
- Lund University,Lunds universitet,Antioxidationsmedicin,Forskargrupper vid Lunds universitet,Antioxidation medicine,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- Engelska.
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Ingår i: Free Radical Biology and Medicine. - : Elsevier BV. - 0891-5849. ; 162
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- α1-microglobulin (A1M) is a ubiquitous protein with reductase and radical- and heme-binding properties. The protein is mainly expressed in the liver and encoded by the α1-microglobulin-bikunin precursor (AMBP) gene together with the plasma proteinase inhibitor bikunin. The AMBP polypeptide is translated, glycosylated and the C-terminal bikunin part linked via a chondroitin sulfate glycosaminoglycan chain to one or two heavy chains in the endoplasmic reticulum (ER) and Golgi compartments. After proteolytic cleavage, the A1M protein and complexed bikunin parts are secreted separately. The complete physiological role of A1M, and the reason for the co-synthesis with bikunin, are both still unknown. The aim of this work was to develop an A1M knockout (A1M−KO) mouse model lacking expression of A1M, but with a preserved bikunin expression, and to study the phenotypic traits in these mice, with a focus on hepatic endoplasmic reticulum (ER) function. The bikunin expression was increased in the A1M−KO mouse livers, while the bikunin levels in plasma were decreased, indicating a defective biosynthesis of bikunin. The A1M−KO livers also showed an increased expression of transducers of the unfolded protein response (UPR), indicating an increased ER-stress in the livers. At twelve months of age, the A1M−KO mice also displayed an increased body weight, and an increased liver weight and lipid accumulation. Moreover, the KO mice showed an increased expression of endogenous antioxidants in the liver, but not in the kidneys. Together, these results suggest a physiological role of A1M as a regulator of the intracellular redox environment and more specifically the ER folding and posttranslational modification processes, particularly in the liver.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- AMBP
- Bikunin
- ER-Stress
- Knockout mouse model
- Oxidative stress
- α-microglobulin
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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