ArticleDiabetes2015
Ask1 gene deletion blocks maternal diabetes-induced endoplasmic reticulum stress in the developing embryo by disrupting the unfolded protein response signalosome.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 64 citations in OpenAlex.
- Updated insights on ASK1 signaling: mechanisms, regulation, and therapeutic potential in diseases.Molecular and cellular biochemistry · 2025Review
- Overload of Glucose Metabolism as Initiating Factor in Diabetic Embryopathy and Prevention by Glyoxalase 1 Inducer Dietary Supplement.Antioxidants (Basel, Switzerland) · 2025Article
- Importance of unfolded protein response modulation on diabetes management: a systematic review.Journal of diabetes and metabolic disorders · 2024Review
- Differential responses to maternal diabetes in embryo and visceral yolk sac.Frontiers in cell and developmental biology · 2023Article
- Functional cargos of exosomes derived from Flk-1Communications biology · 2022Article
- Maternal diabetes induces senescence and neural tube defects sensitive to the senomorphic rapamycin.Science advances · 2021Article
- Pharmacological Inhibition of Inositol-Requiring Enzyme 1α RNase Activity Protects Pancreatic Beta Cell and Improves Diabetic Condition in Insulin Mutation-Induced Diabetes.Frontiers in endocrinology · 2021Article
- Deficiency of the oxidative stress-responsive kinase p70S6K1 restores autophagy and ameliorates neural tube defects in diabetic embryopathy.American journal of obstetrics and gynecology · 2020Article
- Mechanisms of Congenital Malformations in Pregnancies with Pre-existing Diabetes.Current diabetes reports · 2020Review
- Review
- Wnt regulates amino acid transporter Slc7a5 and so constrains the integrated stress response in mouse embryos.EMBO reports · 2020Article
- The Reciprocal Causation of the ASK1-JNK1/2 Pathway and Endoplasmic Reticulum Stress in Diabetes-Induced Cognitive Decline.Frontiers in cell and developmental biology · 2020Article
- Trehalose restores functional autophagy suppressed by high glucose.Reproductive toxicology (Elmsford, N.Y.) · 2019Article
- Tip60- and sirtuin 2-regulated MARCKS acetylation and phosphorylation are required for diabetic embryopathy.Nature communications · 2019Article
- Article
- High Glucose Inhibits Neural Stem Cell Differentiation Through Oxidative Stress and Endoplasmic Reticulum Stress.Stem cells and development · 2018Article
- miR199a-5p inhibits hepatic insulin sensitivity via suppression of ATG14-mediated autophagy.Cell death & disease · 2018Article
- The current status and future of cardiac stem/progenitor cell therapy for congenital heart defects from diabetic pregnancy.Pediatric research · 2018Review
- Endoplasmic Reticulum Stress-Induced CHOP Inhibits PGC-1α and Causes Mitochondrial Dysfunction in Diabetic Embryopathy.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Protein kinase C-alpha suppresses autophagy and induces neural tube defects via miR-129-2 in diabetic pregnancy.Nature communications · 2017Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Apoptosis signal-regulating kinase 1 (ASK1) is activated by various stresses. The link between ASK1 activation and endoplasmic reticulum (ER) stress, two causal events in diabetic embryopathy, has not been determined. We sought to investigate whether ASK1 is involved in the unfolded protein response (UPR) that leads to ER stress. Deleting Ask1 abrogated diabetes-induced UPR by suppressing phosphorylation of inositol-requiring enzyme 1α (IRE1α), and double-stranded RNA-activated protein kinase (PKR)-like ER kinase (PERK) blocked the mitochondrial translocation of proapoptotic Bcl-2 members and ER stress. ASK1 participated in the IRE1α signalosome, and removing ASK1 abrogated the proapoptotic kinase activity of IRE1α. Ask1 deletion suppressed diabetes-induced IRE1α endoriboneclease activities, which led to X-box binding protein 1 mRNA cleavage, an ER stress marker, decreased expression of microRNAs, and increased expression of a miR-17 target, thioredoxin-interacting protein (Txnip), a thioredoxin binding protein, which enhanced ASK1 activation by disrupting the thioredoxin-ASK1 complexes. ASK1 is essential for the assembly and function of the IRE1α signalosome, which forms a positive feedback loop with ASK1 through Txnip. ASK1 knockdown in C17.2 neural stem cells diminished high glucose- or tunicamycin-induced IRE1α activation, which further supports our hypothesis that ASK1 plays a causal role in diabetes-induced ER stress and apoptosis.
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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.