Morphological Changes in Diabetic Kidney Are Associated with Increased O-GlcNAcylation of Cytoskeletal Proteins Including α-actinin 4

Overview

Journal Clin Proteomics

Publisher Biomed Central

Date 2011 Sep 22

PMID 21933451

Citations 12

Authors

Yoshihiro Akimoto

Yuri Miura

Tosifusa Toda

Margreet A Wolfert

Lance Wells

Geert-Jan Boons

Gerald W Hart

Tamao Endo

Hayato Kawakami

Affiliations

Soon will be listed here.

Abstract

Purpose: The objective of the present study is to identify proteins that change in the extent of the modification with O-linked N-acetylglucosamine (O-GlcNAcylation) in the kidney from diabetic model Goto-Kakizaki (GK) rats, and to discuss the relation between O-GlcNAcylation and the pathological condition in diabetes.

Methods: O-GlcNAcylated proteins were identified by two-dimensional gel electrophoresis, immunoblotting and peptide mass fingerprinting. The level of O-GlcNAcylation of these proteins was examined by immunoprecipitation, immunoblotting and in situ Proximity Ligation Assay (PLA).

Results: O-GlcNAcylated proteins that changed significantly in the degree of O-GlcNAcylation were identified as cytoskeletal proteins (α-actin, α-tubulin, α-actinin 4, myosin) and mitochondrial proteins (ATP synthase β, pyruvate carboxylase). The extent of O-GlcNAcylation of the above proteins increased in the diabetic kidney. Immunofluorescence and in situ PLA studies revealed that the levels of O-GlcNAcylation of actin, α-actinin 4 and myosin were significantly increased in the glomerulus and the proximal tubule of the diabetic kidney. Immunoelectron microscopy revealed that immunolabeling of α-actinin 4 is disturbed and increased in the foot process of podocytes of glomerulus and in the microvilli of proximal tubules.

Conclusion: These results suggest that changes in the O-GlcNAcylation of cytoskeletal proteins are closely associated with the morphological changes in the podocyte foot processes in the glomerulus and in microvilli of proximal tubules in the diabetic kidney. This is the first report to show that α-actinin 4 is O-GlcNAcylated. α-Actinin 4 will be a good marker protein to examine the relation between O-GlcNAcylation and diabetic nephropathy.

Citing Articles

O-linked β-N-acetylglucosamine (O-GlcNAc) modification: Emerging pathogenesis and a therapeutic target of diabetic nephropathy.

Qi B, Chen Y, Chai S, Lu X, Kang L Diabet Med. 2024; 42(2):e15436.

PMID: 39279604 PMC: 11733667. DOI: 10.1111/dme.15436.

ER Stress-Perturbed Intracellular Protein O-GlcNAcylation Aggravates Podocyte Injury in Diabetes Nephropathy.

Song S, Hu T, Shi X, Jin Y, Liu S, Li X Int J Mol Sci. 2023; 24(24).

PMID: 38139429 PMC: 10743520. DOI: 10.3390/ijms242417603.

O-GlcNAcylation: an important post-translational modification and a potential therapeutic target for cancer therapy.

Lu Q, Zhang X, Liang T, Bai X Mol Med. 2022; 28(1):115.

PMID: 36104770 PMC: 9476278. DOI: 10.1186/s10020-022-00544-y.

-GlcNAcylation and phosphorylation of β-actin Ser in diabetic nephropathy.

Akimoto Y, Yan K, Miura Y, Tsumoto H, Toda T, Fukutomi T Am J Physiol Renal Physiol. 2019; 317(5):F1359-F1374.

PMID: 31566433 PMC: 6879942. DOI: 10.1152/ajprenal.00566.2018.

Vitamin D suppresses cellular pathways of diabetes complication in liver.

Derakhshanian H, Djalali M, Mohammad Hassan M, Alvandi E, Eshraghian M, Mirshafiey A Iran J Basic Med Sci. 2019; 22(6):690-694.

PMID: 31231498 PMC: 6570757. DOI: 10.22038/ijbms.2019.36054.8584.

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