Alteration of autophagy-related protein 5 (ATG5) levels and Atg5 gene expression in diabetes mellitus with and without complications.

Remah Yassin, Hagar Tadmor, Evgeny Farber, Anas Igbariye, Aida Armaly-Nakhoul, Inbal Dahan, Farid Nakhoul, Nakhoul Nakhoul

Diabetes & vascular disease research 2021 Nov-Dec

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Autophagy is a catabolic mechanism that involves lysosomal-dependent degradation of unnecessary intracellular components and responsible for normal cellular homeostasis. Autophagy pathway and its key participant ATG5/LC3 are associated with several pathologies such as diabetes mellitus and its complications. Levels and expression of autophagy key components ATG5 and LC3B were analyzed in both human model and murine tissues. One hundred and twenty human subjects were divided into four groups: Healthy (control), diabetes mellitus without complications, diabetic nephropathy, and diabetic retinopathy. Additionally, we used kidneys from WT healthy and diabetic nephropathy mice. Lysate derived from human peripheral blood mononuclear cells and murine renal cortex lysates were subjected to western blot and immunohistochemical analysis. Western blot and immunohistochemical analysis demonstrate that ATG5 protein levels were significantly decreased in diabetes mellitus, diabetic nephropathy (DN), and diabetic retinopathy patients versus healthy controls and in DN mice compared to healthy mice (0.65 ± 0.04; 1.15 ± 0.13 A.U. units, respectively). Quantification of staining area (%) of ATG5 mice tissue expression also decreased in DN versus healthy mice (4.42 ± 1.08%; 10.87 ± 1.01%, respectively). Significant reduction in peripheral blood mononuclear cells in diabetic patients (with or without complications) vs. healthy controls. Renal LC3B levels were lower in DN versus healthy mice (0.36 ± 0.03; 0.68 ± 0.07 A.U. units). Renal LC3B staining quantification revealed significant reduction in DN versus healthy mice (1.7 ± 0.23%; 8.56 ± 1.7%). We conclude that ATG5, as well as LC3B, are down regulated in diabetic patients with or without complications. This diminution contributes to deficiencies in the autophagy process.

Citation

Remah Yassin, Hagar Tadmor, Evgeny Farber, Anas Igbariye, Aida Armaly-Nakhoul, Inbal Dahan, Farid Nakhoul, Nakhoul Nakhoul. Alteration of autophagy-related protein 5 (ATG5) levels and Atg5 gene expression in diabetes mellitus with and without complications. Diabetes & vascular disease research. 2021 Nov-Dec;18(6):14791641211062050