Journal: iScience

Article Title: Sulfonylurea receptor 1 deficiency alleviates acute lung injury by activating PARP1 in epithelial cells

doi: 10.1016/j.isci.2026.117627

Figure Lengend Snippet: SUR1 interacted with PARP1 to suppress DNA damage repair and induce apoptosis of bronchial epithelial cells (A) Co-immunoprecipitation and western blot analyses of HEK293T cells transfected with FLAG-SUR1 plasmids (left) or human bronchial epithlial (HBE) cells (right). (B) Immunofluorescence staining of HBE cells. Scale bars, 25 μm. (C) Homologous recombination reporter assay in U2OS-DRGFP cells transfected with SUR1 siRNA, followed by flow cytometry analysis. (D) Western blot analysis of HBE cells transfected with SUR1 siRNAs with or without 20 ng/mL TNF-α or 50 μg/mL LPS treatment for 1 h. (E) ROS levels in HBE cells with SUR1 knockdown, treated with or without TNF-α 20 ng/mL for 3 h. (F) Apoptosis assay by flow cytometry in HBE cells transfected with SUR1 siRNAs and treated with TNF-α. Data are presented as mean ± SD ( n = 3). ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001. Co-localization in (B) was assessed using Pearson’s correlation coefficient. Data in (C–F) were analyzed using two-way ANOVA followed by Tukey’s multiple-comparisons test. Representative images are shown.

Article Snippet: Recombinant human TNF-α protein , ABclonal Biotechnology , Cat# RP00001.

Techniques: Co-Immunoprecipitation Assay, Western Blot, Transfection, Immunofluorescence, Staining, Homologous Recombination, Reporter Assay, Flow Cytometry, Analysis, Knockdown, Apoptosis Assay

Journal: iScience

Article Title: Sulfonylurea receptor 1 deficiency alleviates acute lung injury by activating PARP1 in epithelial cells

doi: 10.1016/j.isci.2026.117627

Figure Lengend Snippet: Glibenclamide disrupted SUR1-PARP1 interaction to restore DNA repair and attenuate apoptosis and inflammation in HBE cells (A) Schematic diagram of HBE cells with different treatments, followed by RNA sequencing analysis. Groups: control, 20 ng/mL; TNF-α, 100 μmol/L; glibenclamide plus TNF-α. n = 2 per group. (B) Venn diagram of differentially expressed genes. (C) GO and KEGG enrichment analyses of 280 genes in the intersection shown in (B). (D) RT-qPCR analysis of HBE cells with different treatments as indicated. (E) Co-immunoprecipitation assay in HBE cells transfected with FLAG-SUR1 plasmids and treated with 20 ng/mL TNF-α or 100 μmol/L glibenclamide as indicated. L.E., long exposure. (F) HBE cells were treated as in (E), then subjected to cytoplasmic and nuclear protein fractionation followed by western blotting. Cyto, cytoplasm; Nu, nucleus. (G) Western blot analysis of HBE cells pretreated with 100 μmol/L glibenclamide for 30 min followed by TNF-α or LPS co-treatment for 1 h. (H–J) ROS production, caspase-3 activity, and apoptosis in HBE cells under indicated treatments. (K–M) HBE cells were pretreated with 100 μmol/L glibenclamide, 5 μmol/L olaparib, or their combination for 24 h, followed by 20 ng/mL TNF-α stimulation, and subjected to western blotting, caspase-3 activity assay, and apoptosis analysis by flow cytometry. Gli, glibenclamide. Data are presented as mean ± SD ( n = 3). ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001. GO and KEGG enrichment analyses in (C) were performed using a hypergeometric test with false discovery rate (FDR) correction. Data in (D) and (G–M) were analyzed using one-way ANOVA followed by Tukey’s multiple-comparisons test. Representative images are shown.

Article Snippet: Recombinant human TNF-α protein , ABclonal Biotechnology , Cat# RP00001.

Techniques: RNA Sequencing, Analysis, Control, Quantitative RT-PCR, Co-Immunoprecipitation Assay, Transfection, Fractionation, Western Blot, Activity Assay, Caspase-3 Activity Assay, Flow Cytometry

Journal: iScience

Article Title: Sulfonylurea receptor 1 deficiency alleviates acute lung injury by activating PARP1 in epithelial cells

doi: 10.1016/j.isci.2026.117627

Figure Lengend Snippet: Schematic illustration of the role of SUR1 in ALI and the protective mechanism of glibenclamide TNF-α binds to its receptor (TNFR), activating the NF-κB pathway and promoting inflammation through increased transcription of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). In parallel, TNF-α induces mitochondrial dysfunction and ROS production, leading to DNA strand breaks. In response to DNA damage, nuclear PARP1 is activated to recruit DNA repair enzymes, promoting cell survival. Left, SUR1 interacts with and sequesters PARP1, impairing DNA damage repair. Accumulated DNA damage amplifies ROS production and NF-κB activation, which in turn further increases the transcription of inflammatory cytokines. This creates a positive feedback loop that promotes epithelial cell apoptosis and inflammation, contributing to ALI progression. Right, glibenclamide binds to SUR1 and disrupts the SUR1-PARP1 interaction, releasing PARP1 to restore DNA damage repair. This intervention breaks the pathological feedback loop by reducing ROS production, NF-κB activation, and inflammatory cytokine expression, thereby suppressing apoptosis and inflammation in epithelial cells and ultimately protecting against ALI.

Article Snippet: Recombinant human TNF-α protein , ABclonal Biotechnology , Cat# RP00001.

Techniques: Activation Assay, Expressing

Journal: iScience

Article Title: Sulfonylurea receptor 1 deficiency alleviates acute lung injury by activating PARP1 in epithelial cells

doi: 10.1016/j.isci.2026.117627

Figure Lengend Snippet:

Article Snippet: Recombinant human TNF-α protein , ABclonal Biotechnology , Cat# RP00001.

Techniques: Cell-Signaling, Recombinant, Transfection, Caspase-3 Activity Assay, Protein Extraction, Knock-Out, Sequencing, Control, Plasmid Preparation, Software, Analysis