O-GlcNAcylation disrupts STRA6-retinol signals in kidneys of diabetes
Copyright © 2019 Elsevier B.V. All rights reserved..
BACKGROUND: O-GlcNAcylation is an important mechanism of diabetic complication. Retinoid homeostasis regulates cell-physiological functions through STRA6-retinol signaling. Therefore, we investigated whether O-GlcNAcylation disrupted STRA6-retinol signals in diabetes.
METHODS: Immunoprecipitation and proximity ligation assay were used to investigate O-GlcNAcylation of STRA6-retinol signals in kidneys of db/db and ob/ob mice. Western blot and immunohistochemistry were done for STRA6/CRBP1/LRAT/RALDH1/RARs pathway, GFAT, OGT, TGFβ1 and collagen 1 level. HPLC and ELISA for retinol, retinal, and retinoic acid concentrations were performed in vivo and vitro. RBP4 binding with STRA6 was measured in vitro. To verify whether O-GlcNAcylation disrupted STRA6-retinol signals, treatment of TMG and OSMI-1, transfection of OGA and OGT, and OGT siRNA were performed in HK-2 cells.
RESULTS: STRA6 and RALDH1 were highly O-GlcNAc-modified in glomeruli and tubules of db/db and ob/ob mice. RBP4, p-Try, p-JAK2, and p-STAT5 on STRA6 immunoprecipitate were reduced. Cellular retinol signals (CRBP1, LRAT, ADH, retinol, retinal, RA, RARα, RARγ and RXRα) remarkably decreased in kidneys of db/db, ob/ob mice and HG-cultured cells. TMG and OGT transfection induced O-GlcNAcylation of STRA6 and RALDH1, repressed RBP4-bound STRA6, and retinol signals in NG-cultured cells. OSMI-1, OGA transfection, and OGT silence reversed O-GlcNAc-modification of STRA6 and RALDH1, and rescued the decrease of retinol signals, and reversed the increase of TGFβ1 and collagen 1 in HG-treated cells.
CONCLUSIONS: O-GlcNAcylation significantly modified STRA6 and RALDH1, suppressed RBP4 binding activity, and disrupted retinol signals in the kidney of diabetes.
GENERAL SIGNIFICANCE: This study first indicates that STRA6-retinol signals were directly disrupted by O-GlcNAcylation in diabetic kidney.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1863 |
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| Enthalten in: |
Biochimica et biophysica acta. General subjects - 1863(2019), 6 vom: 13. Juni, Seite 1059-1069 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Chao-Hung [VerfasserIn] |
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| Links: |
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| Themen: |
11103-57-4 |
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| Anmerkungen: |
Date Completed 22.01.2020 Date Revised 22.01.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbagen.2019.03.014 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM295281189 |
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| 100 | 1 | |a Chen, Chao-Hung |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a O-GlcNAcylation disrupts STRA6-retinol signals in kidneys of diabetes |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 22.01.2020 | ||
| 500 | |a Date Revised 22.01.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019 Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND: O-GlcNAcylation is an important mechanism of diabetic complication. Retinoid homeostasis regulates cell-physiological functions through STRA6-retinol signaling. Therefore, we investigated whether O-GlcNAcylation disrupted STRA6-retinol signals in diabetes | ||
| 520 | |a METHODS: Immunoprecipitation and proximity ligation assay were used to investigate O-GlcNAcylation of STRA6-retinol signals in kidneys of db/db and ob/ob mice. Western blot and immunohistochemistry were done for STRA6/CRBP1/LRAT/RALDH1/RARs pathway, GFAT, OGT, TGFβ1 and collagen 1 level. HPLC and ELISA for retinol, retinal, and retinoic acid concentrations were performed in vivo and vitro. RBP4 binding with STRA6 was measured in vitro. To verify whether O-GlcNAcylation disrupted STRA6-retinol signals, treatment of TMG and OSMI-1, transfection of OGA and OGT, and OGT siRNA were performed in HK-2 cells | ||
| 520 | |a RESULTS: STRA6 and RALDH1 were highly O-GlcNAc-modified in glomeruli and tubules of db/db and ob/ob mice. RBP4, p-Try, p-JAK2, and p-STAT5 on STRA6 immunoprecipitate were reduced. Cellular retinol signals (CRBP1, LRAT, ADH, retinol, retinal, RA, RARα, RARγ and RXRα) remarkably decreased in kidneys of db/db, ob/ob mice and HG-cultured cells. TMG and OGT transfection induced O-GlcNAcylation of STRA6 and RALDH1, repressed RBP4-bound STRA6, and retinol signals in NG-cultured cells. OSMI-1, OGA transfection, and OGT silence reversed O-GlcNAc-modification of STRA6 and RALDH1, and rescued the decrease of retinol signals, and reversed the increase of TGFβ1 and collagen 1 in HG-treated cells | ||
| 520 | |a CONCLUSIONS: O-GlcNAcylation significantly modified STRA6 and RALDH1, suppressed RBP4 binding activity, and disrupted retinol signals in the kidney of diabetes | ||
| 520 | |a GENERAL SIGNIFICANCE: This study first indicates that STRA6-retinol signals were directly disrupted by O-GlcNAcylation in diabetic kidney | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Diabetes | |
| 650 | 4 | |a Diabetic nephropathy | |
| 650 | 4 | |a O-GlcNAc | |
| 650 | 4 | |a RALDH | |
| 650 | 4 | |a RBP4 | |
| 650 | 4 | |a Retinol | |
| 650 | 4 | |a STRA6 | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 650 | 7 | |a Stra6 protein, mouse |2 NLM | |
| 650 | 7 | |a Vitamin A |2 NLM | |
| 650 | 7 | |a 11103-57-4 |2 NLM | |
| 700 | 1 | |a Lin, Kun-Der |e verfasserin |4 aut | |
| 700 | 1 | |a Ke, Liang-Yin |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Chan-Jung |e verfasserin |4 aut | |
| 700 | 1 | |a Kuo, Wen-Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Mei-Yueh |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Yu-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Hsiao, Pi-Jung |e verfasserin |4 aut | |
| 700 | 1 | |a Hsu, Chih-Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Shin, Shyi-Jang |e verfasserin |4 aut | |
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