General Control of Amino Acid Synthesis 5-Like 1-Mediated Acetylation of Manganese Superoxide Dismutase Regulates Oxidative Stress in Diabetic Kidney Disease.

Abstract

Diabetic kidney disease (DKD) is the major cause of end-stage renal disease (ESRD). In the past few decades, there has been a large amount of evidence to highlight the pivotal role of oxidative stress in the development and progression of DKD. However, the detailed molecular mechanisms are not fully elucidated. A new sight has been established that the mitochondrial acetyltransferase GCN5L1 participates in cellular redox homeostasis maintenance in DKD. Firstly, we found that the expression of GCN5L1 is significantly elevated both in human and mouse kidney tissues with DKD and in hyperglycemic renal tubular epithelial cells (TECs), while deletion of GCN5L1 could effectively ameliorate oxidative stress-induced renal injury in DKD. Furthermore, deletion of GCN5L1 could reduce MnSOD acetylation on lysine 68 and activate its activity, thereby scavenging excessive ROS and relieving oxidative stress-induced renal inflammation and fibrosis. In general, GCN5L1-mediated acetylation of MnSOD exacerbated oxidative stress-induced renal injury, suggesting that GCN5L1 might be a potential intervention target in DKD.

• Authors: Tingting Lv, Yao Lu, Yi Liu, Hong Feng, Chensheng Li, Wei Sheng, Zhengguo Cui, Suwei Zhu, Xia Gu, Zhe Yang, Qiang Wan
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2021 Pg. 6691226 ( 2021) ISSN: 1942-0994 [Electronic] United States
• PMID: 33680286 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Tingting Lv et al.

Chemical References

• BLOC1S1 protein, human
• BLOC1S1 protein, mouse
• Mitochondrial Proteins
• Nerve Tissue Proteins
• Reactive Oxygen Species
• Streptozocin
• Superoxide Dismutase
• Glucose
• Lysine

Topics

• Acetylation (drug effects)
• Animals
• Cell Line
• Diabetic Nephropathies (complications, pathology)
• Disease Models, Animal
• Down-Regulation (drug effects, genetics)
• Epithelial Cells (metabolism, pathology)
• Epithelial-Mesenchymal Transition (drug effects)
• Glucose (toxicity)
• Humans
• Inflammation (pathology)
• Kidney Tubules (pathology)
• Lysine (metabolism)
• Male
• Mice, Inbred C57BL
• Mitochondrial Proteins (metabolism)
• Nerve Tissue Proteins (metabolism)
• Oxidative Stress (drug effects)
• Proteinuria (complications, pathology)
• Reactive Oxygen Species (metabolism)
• Streptozocin
• Superoxide Dismutase (metabolism)
• Ubiquitination
• Mice