ArticleProceedings of the National Academy of Sciences of the United States of America2012
H2O2 activates G protein, α 12 to disrupt the junctional complex and enhance ischemia reperfusion injury.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 48 citations in OpenAlex.
- KIM-1: A Non-Invasive Marker for Kidney Injury and Treatment Efficacy in FMF.Mediterranean journal of rheumatology · 2026Article
- Review
- GRespiratory research · 2024Review
- Sphingosine 1-Phosphate Receptor 5 (S1PInternational journal of molecular sciences · 2022Article
- Review
- GαFrontiers in cell and developmental biology · 2022Review
- VIP Stabilizes the Cytoskeleton of Schlemm's Canal Endothelia via Reducing Caspase-3 Mediated ZO-1 Endolysosomal Degradation.Oxidative medicine and cellular longevity · 2021Article
- Functional roles of Grainyhead-like transcription factors in renal development and disease.Pediatric nephrology (Berlin, Germany) · 2020Review
- Gα-13 induces CThe Journal of biological chemistry · 2019Article
- ZO-1 protein is required for hydrogen peroxide to increase MDCK cell paracellular permeability in an ERK 1/2-dependent manner.American journal of physiology. Cell physiology · 2018Article
- Impaired autophagy bridges lysosomal storage disease and epithelial dysfunction in the kidney.Nature communications · 2018Article
- Redox regulation of the actin cytoskeleton and its role in the vascular system.Free radical biology & medicine · 2017Review
- Pharmacological inhibition of Src kinase protects against acute kidney injury in a murine model of renal ischemia/reperfusion.Oncotarget · 2017Article
- Ultrasound Detection of Regional Oxidative Stress in Deep Tissues Using Novel Enzyme Loaded Nanoparticles.Advanced healthcare materials · 2017Article
- G protein αAmerican journal of physiology. Renal physiology · 2016Article
- Occludin Content Modulates Hydrogen Peroxide-Induced Increase in Renal Epithelial Paracellular Permeability.Journal of cellular biochemistry · 2016Article
- Apoptosis inhibitor of macrophage protein enhances intraluminal debris clearance and ameliorates acute kidney injury in mice.Nature medicine · 2016Article
- Stimulation of Dopamine D3 Receptor Attenuates Renal Ischemia-Reperfusion Injury via Increased Linkage With Gα12.Transplantation · 2015Article
- The protein kinase 2 inhibitor tetrabromobenzotriazole protects against renal ischemia reperfusion injury.Scientific reports · 2015Article
- Chloride transporters and receptor-mediated endocytosis in the renal proximal tubule.The Journal of physiology · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The epithelial cell tight junction separates apical and basolateral domains and is essential for barrier function. Disruption of the tight junction is a hallmark of epithelial cell damage and can lead to end organ damage including renal failure. Herein, we identify Gα12 activation by H(2)O(2) leading to tight junction disruption and demonstrate a critical role for Gα12 activation during bilateral renal ischemia/reperfusion injury. Madin-Darby canine kidney (MDCK) cells with inducible Gα12 (Gα12-MDCK) and silenced Gα12 (shGα12-MDCK) were subjected to ATP depletion/repletion and H(2)O(2)/catalase as models of tight junction disruption and recovery by monitoring transepithelial resistance. In ATP depleted cells, barrier disruption and recovery was not affected by Gα12, but reassembly was accelerated by Gα12 depletion. In contrast, silencing of Gα12 completely protected cells from H(2)O(2)-stimulated barrier disruption, a response that rapidly occurred in control cells. H(2)O(2) activated Src and Rho, and Src inhibition (by PP2), but not Rho (by Y27632), protected cells from H(2)O(2)-mediated barrier disruption. Immunofluorescent and biochemical analysis showed that H(2)O(2) led to increased tyrosine phosphorylation of numerous proteins and altered membrane localization of tight junction proteins through Gα12/Src signaling pathway. Gα12 and Src were activated in vivo during ischemia/reperfusion injury, and transgenic mice with renal tubular QLα12 (activated mutant) expression were delayed in recovery and showed more extensive injury. Conversely, Gα12 knockout mice were nearly completely protected from ischemia/reperfusion injury. Taken together, these studies reveal that ROS stimulates Gα12 to activate injury pathways and identifies a therapeutic target for ameliorating ROS mediated injury.
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.