P53/NRF2 mediates SIRT1's protective effect on diabetic nephropathy

Publication date: Available online 6 April 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Fuzhe Ma, Junduo Wu, Ziping Jiang, Wenlin Huang, Ye Jia, Weixia Sun, Hao WuAbstractDiabetic nephropathy (DN) is the leading cause of end stage renal disease, posing a severe threat to public health. Previous studies reported the protective role of sirtuin 1 (SIRT1) in DN, encouraging the investigation of more potent and specific SIRT1 activators. SRT2104 is a novel, first-in-class, highly selective small-molecule activator of SIRT1, with its effect and mechanism unknown on DN. To this end, streptozotocin-induced C57BL/6 wild-type (WT) diabetic mice were treated with SRT2104, for 24 weeks. To determine whether SRT2104 acted through inhibition of P53 – a substrate of SIRT1, the P53 activator nutlin3a was administered to the WT diabetic mice in the presence of SRT2104. In order to test whether nuclear factor erythroid 2-related factor 2 (NRF2) – the master of cellular antioxidants – mediated SIRT1 and P53's actions, WT and Nrf2 gene knockout (KO) diabetic mice were treated with SRT2104 or the P53 inhibitor pifithrin-α (PFT-α). In the WT mice, SRT2104 enhanced renal SIRT1 expression and activity, deacetylated P53, and activated NRF2 antioxidant signaling, providing remarkable protection against the DM-induced renal oxidative stress, inflammation, fibrosis, glomerular remodeling and albuminuria. These effects were completely...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - Category: Molecular Biology Source Type: research

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Conversations and healthy debate about issues facing our industry and the health care system are critical to addressing some of today ’s challenges and opportunities. The Catalyst welcomes guest contributors, including patients, stakeholders, innovators and others, to share their perspectives and point of view. Views represented here may not be those of PhRMA, though they are no less key to a healthy dialogue on issues in health care today.
Source: The Catalyst - Category: Pharmaceuticals Authors: Tags: diabetes Out of Pocket Costs Voters for Cures Source Type: news
The latest crowdfunded research project undertaken by the SENS Research Foundation involves using the genetically engineered maximally modifiable mouse lineage in order to demonstrate the ability to copy a version of the ATP8 mitochondrial gene into the cell nucleus, a process known as allotopic expression, and thus prevent mutational damage to this gene from degrading mitochondrial function. This is a modest step on the road towards bringing this class of genetic engineering project to the point of readiness for commercial development, when a biotech startup company could be created to carry it forward. In just a f...
Source: Fight Aging! - Category: Research Authors: Tags: Activism, Advocacy and Education Source Type: blogs
The Food and Drug Administration approved AstraZeneca's drug Farxiga as a treatment for reducing the risk of hospitalizations for heart failure in adults with type-2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors. Farxiga, developed by AstraZeneca (NYSE: AZN) in a partnership with Bristol-Myers Squibb, already had FDA approval as a therapy along with diet and exercise to lower blood sugar in adults with type 2 diabetes. The drug generated sales of more than…
Source: bizjournals.com Health Care:Pharmaceuticals headlines - Category: Pharmaceuticals Authors: Source Type: news
Review in-depth clinical information, latest medical news, and guidelines on prevention and treatment of microvascular complications of diabetes, including diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy.
Source: Medscape Today Headlines - Category: Consumer Health News Tags: Resource Center Source Type: news
Publication date: Available online 21 October 2019Source: Molecular and Cellular EndocrinologyAuthor(s): Huiwen Ren, Ying Shao, Can Wu, Xiaoyu Ma, Chuan Lv, Qiuyue WangAbstractMetformin, as the basic pharmacological therapy and the first preventive drug in type 2 diabetes mellitus (T2DM), is proved to have potential protection in diabetic kidney disease (DKD). Here, we established a diabetic rat model induced by high-fat diet and low dose streptozotocin, and high glucose cultured rat mesangial cells (RMCs) pre-treated with metformin or transfected with AMPK, SIRT1 and FoxO1 small interfering RNA, and detected oxidative str...
Source: Molecular and Cellular Endocrinology - Category: Endocrinology Source Type: research
The Mickschl family in Minnesota creates hand-made Cure Mittens in crazy colors to raise awareness and money for type 1 diabetes.
Source: Diabetes Mine - Category: Endocrinology Authors: Source Type: blogs
ConclusionA considerable burden of previously unknown AF was detected when long-term monitoring was applied in at-risk patients. Biomarkers were associated with AF incidence and improved prediction of long AF episodes.
Source: American Heart Journal - Category: Cardiology Source Type: research
Publication date: Available online 20 October 2019Source: American Heart JournalAuthor(s): Neha J. Pagidipati, Yinggan Zheng, Jennifer B. Green, Darren K. McGuire, Robert J. Mentz, Svati Shah, Pablo Aschner, Tuncay Delibasi, Helena W. Rodbard, Cynthia M. Westerhout, Rury R. Holman, Eric D. Peterson, on behalf of the TECOS Study GroupAbstractBackgroundObesity is a risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). Whether obesity affects outcomes among those with T2D and atherosclerotic CVD (ASCVD) remains uncertain. Our objective was to investigate the relationship between body mass index (BMI) and ASC...
Source: American Heart Journal - Category: Cardiology Source Type: research
ConclusionsIn this observational analysis of T2D and ASCVD, baseline beta-blocker use was not associated with risks for severe hypoglycemia yet also was not associated with CV risk reduction over 3 years of follow-up, supporting a randomized examination of chronic beta-blocker therapy in this patient population. (TECOS ClinicalTrials.gov number, NCT00790205).
Source: American Heart Journal - Category: Cardiology Source Type: research
DiscussionGiven the multiorgan system potential adverse side effects of prednisone, proving noninferiority of an alternate regimen would be sufficient to make the alternative compare favorably to standard dose steroids. This is the first ever clinical trial in cardiac sarcoidosis and thus in addition to the listed goals of the trial, we will also establish a multi-center, multinational cardiac sarcoidosis clinical trials network. Such a collaborative infrastructure will enable a new era of high quality data to guide physicians when treating cardiac sarcoidosis patients.
Source: American Heart Journal - Category: Cardiology Source Type: research
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