ArticleThe Journal of biological chemistry2010
AMP-activated protein kinase (AMPK) negatively regulates Nox4-dependent activation of p53 and epithelial cell apoptosis in diabetes.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
159 citing papers in PubMed, 248 citations in OpenAlex.
- Review
- Elevated glucose in kidney organoids induces tissue-intrinsic inflammation driving epithelial detachment.Stem cell reports · 2026Article
- Mitochondrial dysfunction as a key player in aggravating periodontitis among diabetic patients: review of the current scope of knowledge.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- High glucose couples DJ-1 with PTEN to activate PDGFRβ for renal proximal tubular cell injury.PloS one · 2025Article
- Effect of Metformin on Peripheral Nerve Morphology in Type 2 Diabetes: A Cross-Sectional Observational Study.Diabetes · 2024Observational
- Vitamin C in the Management of Thyroid Cancer: A Highway to New Treatment?Antioxidants (Basel, Switzerland) · 2024Review
- Exploring the Interplay between Cellular Senescence, Immunity, and Fibrosing Interstitial Lung Diseases: Challenges and Opportunities.International journal of molecular sciences · 2024Review
- AMPK pathway: an emerging target to control diabetes mellitus and its related complications.Journal of diabetes and metabolic disorders · 2024Review
- Protective Factors and the Pathogenesis of Complications in Diabetes.Endocrine reviews · 2024Review
- AMPK Signaling Pathway as a Potential Therapeutic Target for Parkinson's Disease.Advanced pharmaceutical bulletin · 2024Review
- Nicotinamide adenine dinucleotide phosphate oxidase in pancreatic diseases: Mechanisms and future perspectives.World journal of gastroenterology · 2024Review
- Beneficial Effects of Low-Grade Mitochondrial Stress on Metabolic Diseases and Aging.Yonsei medical journal · 2024Review
- Mitochondrial dysfunction in diabetic nephropathy: insights and therapeutic avenues from traditional Chinese medicine.Frontiers in endocrinology · 2024Review
- The Hepatic Antisteatosis Effect of Xanthohumol in High-Fat Diet-Fed Rats Entails Activation of AMPK as a Possible Protective Mechanism.Foods (Basel, Switzerland) · 2023Article
- Sex differences in obesity-induced renal lipid accumulation revealed by lipidomics: a role of adiponectin/AMPK axis.Biology of sex differences · 2023Article
- Insight into the Molecular Mechanism of Diabetic Kidney Disease and the Role of Metformin in Its Pathogenesis.International journal of molecular sciences · 2023Review
- Nox4 as a novel therapeutic target for diabetic vascular complications.Redox biology · 2023Review
- Echinochrome A Prevents Diabetic Nephropathy by Inhibiting the PKC-Iota Pathway and Enhancing Renal Mitochondrial Function in db/db Mice.Marine drugs · 2023Article
- SGLT2 Inhibitor-Dapagliflozin Attenuates Diabetes-Induced Renal Injury by Regulating Inflammation through a CYP4A/20-HETE Signaling Mechanism.Pharmaceutics · 2023Article
- A Review ofMolecules (Basel, Switzerland) · 2023Review
99 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Diabetes and high glucose (HG) increase the generation of NADPH oxidase-derived reactive oxygen species and induce apoptosis of glomerular epithelial cells (podocytes). Loss of podocytes contributes to albuminuria, a major risk factor for progression of kidney disease. Here, we show that HG inactivates AMP-activated protein kinase (AMPK), up-regulates Nox4, enhances NADPH oxidase activity, and induces podocyte apoptosis. Activation of AMPK blocked HG-induced expression of Nox4, NADPH oxidase activity, and apoptosis. We also identified the tumor suppressor protein p53 as a mediator of podocyte apoptosis in cells exposed to HG. Inactivation of AMPK by HG up-regulated the expression and phosphorylation of p53, and p53 acted downstream of Nox4. To investigate the mechanism of podocyte apoptosis in vivo, we used OVE26 mice, a model of type 1 diabetes. Glomeruli isolated from these mice showed decreased phosphorylation of AMPK and enhanced expression of Nox4 and p53. Pharmacologic activation of AMPK by 5-aminoimidazole-4-carboxamide-1-riboside in OVE26 mice attenuated Nox4 and p53 expression. Administration of 5-aminoimidazole-4-carboxamide-1-riboside also prevented renal hypertrophy, glomerular basement thickening, foot process effacement, and podocyte loss, resulting in marked reduction in albuminuria. Our results uncover a novel function of AMPK that integrates metabolic input to Nox4 and provide new insight for activation of p53 to induce podocyte apoptosis. The data indicate the potential therapeutic utility of AMPK activators to block Nox4 and reactive oxygen species generation and to reduce urinary albumin excretion in type 1 diabetes.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.