ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2006
Thioredoxin-ASK1 complex levels regulate ROS-mediated p38 MAPK pathway activity in livers of aged and long-lived Snell dwarf mice.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 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
103 citing papers in PubMed, 206 citations in OpenAlex.
- Plant derived tannic acid-based tissue adhesives: From mechanism to advanced design.Acta biomaterialia · 2026Review
- Gnetum montanum extract attenuates lipopolysaccharide induced acute lung inflammation through Nrf2 and heme oxygenase 1 mediated redox modulation in macrophages.Scientific reports · 2026Article
- Molecular Regulation of FOXO1 and Its Pathophysiological Significance in Endometriosis: A Narrative Review.Antioxidants (Basel, Switzerland) · 2025Review
- Klotho in age-related cardiovascular diseases: Insights into mitochondrial dysfunction and cell death.International journal of cardiology. Heart & vasculature · 2025Review
- Parkinson's disease models and death signaling: what do we know until now?Frontiers in neuroanatomy · 2024Review
- Reactive oxygen species (ROS) scavenging biomaterials for anti-inflammatory diseases: from mechanism to therapy.Journal of hematology & oncology · 2023Review
- MiR-206 may regulate mitochondrial ROS contribute to the progression of Myocardial infarction via TREM1.BMC cardiovascular disorders · 2023Article
- Canagliflozin shares common mTOR and MAPK signaling mechanisms with other lifespan extension treatments.Life sciences · 2023Article
- Tat-CIAPIN1 Prevents Pancreatic β-Cell Death in hIAPP-Induced RINm5F Cells and T2DM Animal Model.International journal of molecular sciences · 2023Article
- Canagliflozin Delays Aging of HUVECs Induced by Palmitic Acid via the ROS/p38/JNK Pathway.Antioxidants (Basel, Switzerland) · 2023Article
- Metabolic Regulation: A Potential Strategy for Rescuing Stem Cell Senescence.Stem cell reviews and reports · 2022Review
- Glutathione S-transferase Mu 2 inhibits hepatic steatosis via ASK1 suppression.Communications biology · 2022Article
- Rapamycin, Acarbose and 17α-estradiol share common mechanisms regulating the MAPK pathways involved in intracellular signaling and inflammation.Immunity & ageing : I & A · 2022Article
- Thioredoxin-1 mediates neuroprotection of Schisanhenol against MPPScientific reports · 2021Article
- Ginsenoside Rg1 ameliorates aging‑induced liver fibrosis by inhibiting the NOX4/NLRP3 inflammasome in SAMP8 mice.Molecular medicine reports · 2021Article
- Titanium Dioxide Nanoparticles Exacerbate Allergic Airway Inflammation via TXNIP Upregulation in a Mouse Model of Asthma.International journal of molecular sciences · 2021Article
- Ethaselen synergizes with oxaliplatin in tumor growth inhibition by inducing ROS production and inhibiting TrxR1 activity in gastric cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- OGDH is involved in sepsis induced acute lung injury through the MAPK pathway.Journal of thoracic disease · 2021Article
- Article
- Mouse models of growth hormone deficiency.Reviews in endocrine & metabolic disorders · 2021Review
43 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
2 authors at 1 institution in 1 country.
Funding
Abstract
We have proposed that the age-associated increase of reactive oxygen species (ROS) by electron transport chain (ETC) dysfunction may cause the elevated basal level of p38 MAPK stress response pathway activity. However, the mechanism by which ROS activates this pathway is not clear. Here we propose that activation of the p38 MAPK pathway by complex I (CI) generated ROS, in response to rotenone (ROT) treatment, is based on the ability of reduced Trx to bind to and inhibit ASK 1 and its release from the complex upon oxidation. This balance of free vs. bound ASK1 regulates the level of p38 MAPK pathway activity. To support this mechanism we demonstrate that the production of ROS by ROT treated AML12 hepatocyte cells dissociates the Trx-ASK1 complex, thereby increasing p38 MAPK pathway activity. This mechanism is supported by the ability of N-acetyl cysteine (NAC) to prevent dissociation of Trx-ASK1 and activation of the p38 MAPK pathway. We also demonstrated that the ratio of ASK1/Trx-ASK1 increases in aged mouse livers and that this correlates with the increased basal activity of the p38 MAPK pathway. The longevity of Snell dwarf mice has been attributed to their resistance to oxidative stress. A comparison of the levels of Trx-ASK1 in young and aged dwarfs showed a higher abundance of the complex than in their age-matched controls. These results, which are indicative of a decreased level of oxidative stress, suggest that increased ROS production in aged liver may alter the ratio of ASK1 and Trx-ASK1, thereby increasing the age-associated basal level of p38 MAPK pathway activity.
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.