ArticleCurrent neurovascular research2010
Early apoptotic vascular signaling is determined by Sirt1 through nuclear shuttling, forkhead trafficking, bad, and mitochondrial caspase activation.
Article in Current neurovascular research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
What it found
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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
70 citing papers in PubMed, 101 citations in OpenAlex.
- Oxidative stress, aging, metabolism, SIRT1, and the gut microbiota: the neurocardiac basis of cognitive loss.Medical gas research · 2027Review
- Article
- SIRT1: The first key to unlocking the mystery of cardiovascular diseases.Frontiers in pharmacology · 2025Review
- Review
- Cognitive Impairment in Multiple Sclerosis.Bioengineering (Basel, Switzerland) · 2023Review
- Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System.Biomolecules · 2023Review
- The Metabolic Basis for Nervous System Dysfunction in Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease.Current neurovascular research · 2023Article
- The impact of aging and oxidative stress in metabolic and nervous system disorders: programmed cell death and molecular signal transduction crosstalk.Frontiers in immunology · 2023Review
- Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2022Review
- The protective effects of 17-β estradiol and SIRT1 against cardiac hypertrophy: a review.Heart failure reviews · 2022Review
- Targeting the core of neurodegeneration: FoxO, mTOR, and SIRT1.Neural regeneration research · 2021Review
- Nicotinamide as a Foundation for Treating Neurodegenerative Disease and Metabolic Disorders.Current neurovascular research · 2021Review
- Sirtuin Control of Mitochondrial Dysfunction, Oxidative Stress, and Inflammation in Chagas Disease Models.Frontiers in cellular and infection microbiology · 2021Review
- New Insights for nicotinamide: Metabolic disease, autophagy, and mTOR.Frontiers in bioscience (Landmark edition) · 2020Review
- Targeting Oxidative Stress and Inflammation to Prevent Ischemia-Reperfusion Injury.Frontiers in molecular neuroscience · 2020Article
- Nicotinamide: Oversight of Metabolic Dysfunction Through SIRT1, mTOR, and Clock Genes.Current neurovascular research · 2020Review
- Dysregulation of metabolic flexibility: The impact of mTOR on autophagy in neurodegenerative disease.International review of neurobiology · 2020Review
- Cellular Compartmentation and the Redox/Nonredox Functions of NADAntioxidants & redox signaling · 2019Article
- Aldose reductase regulates hyperglycemia-induced HUVEC death via SIRT1/AMPK-α1/mTOR pathway.Journal of molecular endocrinology · 2019Article
- The mechanistic target of rapamycin (mTOR) and the silent mating-type information regulation 2 homolog 1 (SIRT1): oversight for neurodegenerative disorders.Biochemical Society transactions · 2018Review
10 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
4 authors at 1 institution in 1 country.
Funding
Abstract
Complications of diabetes mellitus (DM) weigh heavily upon the endothelium that ultimately affect multiple organ systems. These concerns call for innovative treatment strategies that employ molecular pathways responsible for cell survival and longevity. Here we show in a clinically relevant model of DM with elevated D-glucose that endothelial cell (EC) SIRT1 is vital for the prevention of early membrane apoptotic phosphatidylserine externalization and subsequent DNA degradation supported by studies with modulation of SIRT1 activity and gene knockdown of SIRT1. Furthermore, during elevated D-glucose exposure, we show that SIRT1 is sequestered in the cytoplasm of ECs, but specific activation of SIRT1 shuttles the protein to the nucleus to allow for cytoprotection. The ability of SIRT1 to avert apoptosis employs the activation of protein kinase B (Akt1), the post-translational phosphorylation of the forkhead member FoxO3a, the blocked trafficking of FoxO3a to the nucleus, and the inhibition of FoxO3a to initiate a "pro-apoptotic" program as shown by complimentary gene knockdown studies of FoxO3a. Vascular apoptotic oversight by SIRT1 extends to the direct modulation of mitochondrial membrane permeability, cytochrome c release, Bad activation, and caspase 1 and 3 activation, since inhibition of SIRT1 activity and gene knockdown of SIRT1 significantly accentuate cascade progression while SIRT1 activation abrogates these apoptotic elements. Our work identifies vascular SIRT1 and its control over early apoptotic membrane signaling, Akt1 activation, post-translational modification and trafficking of FoxO3a, mitochondrial permeability, Bad activation, and rapid caspase induction as new avenues for the treatment of vascular complications during DM.
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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.