vdac1 oligomerization inhibitor vbit  (TargetMol)

Journal: Journal of Oral Microbiology

Article Title: P. gingivalis induces endothelial dysfunction via mitochondrial fission dependent VDAC1-HK2 disassociation

doi: 10.1080/20002297.2026.2643035

Figure Lengend Snippet: Drp1-dependent VDAC1 oligomerization is required for P. gingivalis induced mitochondrial dysfunction. HAECs was pretreated with or without Mdivi-1 (50 μM) and then infected with P. gingivalis for 24 h (MOI = 100). (A, B) Representative immunofluorescence images and statistics analysis showing the co-location of VDAC1 (red) and p -Drp1 (green) in HAECs. Scale bars: 20 μm (original) and 2 μm (Zoom). (C) The interaction of p -Drp1 and VDAC1 was validated using Co-immunoprecipitation assays. ( n = 3). (D, E) Immunoblot of VDAC1 cross-linking in HAECs pretreated with Mdivi-1 (50 μM) or VBIT-4 (20 μM) and quantitative analysis of oligomers. ( n = 3). (F, G) Calcein, MitoSOX staining assay and quantitative bar chart. Scale bars = 20 μm. ( n = 3) (H, I) Tube formation assay and quantitative bar chart. Scale bars = 200 μm. ( n = 3). Pg, P. gingivalis . All numbers ( n ) are biologically independent experiments. * P < 0.05. *** P < 0.001.

Article Snippet: Mdivi-1, the mPTP inhibitor cyclosporin A (CsA), and the VDAC1 oligomerization inhibitor VBIT-4 were purchased from TargetMol (USA).

Techniques: Infection, Immunofluorescence, Immunoprecipitation, Western Blot, Staining, Tube Formation Assay

Journal: Journal of Oral Microbiology

Article Title: P. gingivalis induces endothelial dysfunction via mitochondrial fission dependent VDAC1-HK2 disassociation

doi: 10.1080/20002297.2026.2643035

Figure Lengend Snippet: P. gingivalis triggers HK2 dissociation from VDAC1. HAECs were pretreated with Mdivi-1 (50 μM) or VBIT-4 (20 μM), followed by infection with P. gingivalis for 24 h. (MOI = 100). (A, B) Representative immunofluorescence images and statistics analysis showing the co-location of VDAC1 (red) and HK2 (green) in HAECs. Scale bars: 20 μm (original) and 5 μm (Zoom). (C) The interaction of VDAC1 and HK2 was validated using Co-immunoprecipitation assays. ( n = 3). (D, E) Representative immunoblots and quantification of HK2 levels in cytosolic and mitochondrial fractions of HAECs ( n = 3). (F, G) Representative immunofluorescence images and statistics analysis showing the co-location of mitochondria (red) and HK2 (green) in HAECs. Scale bars: 20 μm (original) and 5 μm (Zoom). ( n = 3). Pg, P. gingivalis . All numbers ( n ) are biologically independent experiments. ns = not significant. * P < 0.05. ** P < 0.01. *** P < 0.001.

Article Snippet: Mdivi-1, the mPTP inhibitor cyclosporin A (CsA), and the VDAC1 oligomerization inhibitor VBIT-4 were purchased from TargetMol (USA).

Techniques: Infection, Immunofluorescence, Immunoprecipitation, Western Blot

Journal: Proceedings of the National Academy of Sciences of the United States of America

Article Title: Upregulation of the ERRγ-VDAC1 axis underlies the molecular pathogenesis of pancreatitis.

doi: 10.1073/pnas.2219644120

Figure Lengend Snippet: Fig. 4. VDAC1 acts as an effector gene of ERRγ in promoting pancreatitis. (A) Total RNA was isolated from 1° acini cells transduced with adenoviral vectors (Ad) overexpressing GFP or ERRγ for 24 h and analyzed by RNAseq (Top). A volcano plot showing genome-wide changes in mRNA level (Bottom). (B) Heat map depicting the differential expression of genes involved in mitochondrial calcium transport. (C) Analysis of VDAC1 mRNA and protein expression in primary acinar cells following treatment with Ad-ERRγ or Ad-GFP overexpression (10 MOI) for 24 h (two-tailed t test). (D) A putative ERRγ-response element (ERRE) in Vdac1 gene promoter (Left). In vivo chromatin immunoprecipitation (ChIP)-qPCR analysis of ERRγ binding to Vdac1 gene promoter of pancreas harvested from saline (Sal) and caerulein hyperstimulation (CER) pancreatitis conditions (n = 3 mice/group; two-tailed t test). (E) Analysis of VDAC1 mRNA and immunoblot of VDAC1 oligomerization from the pancreas of Errγ+/f and acErrγ+/ mice (n = 3 to 5 mice/group; two-way ANOVA analysis). (F) Analysis of VDAC1 mRNA and immunoblot of VDAC1 oligomerization from the pancreas of preventive caerulein hyperstimulation (CER) pancreatitis model (n = 4 to 6 mice/group; two-way ANOVA analysis). (G) Representative H&E images and histology scoring from the pancreas of mice of preventive caerulein hyperstimulation (CER) pancreatitis model with VDAC1 oligomerization inhibitor, VBIT-12 (20 mg/kg). Animals were killed 16 h after the first saline or caerulein injection. Experimental scheme of this model is described in SI Appendix, Fig. S4D. (H) Immunoblot of VDAC1 oligomerization from the pancreas of mice in G. (I) Serum amylase level and intrapancreatic trypsin activity of mice in (G). (n = 3 to 5 mice/group; two-way ANOVA analysis). Results are representative of those from two independent experiments. Data represent mean ± SEM. ***P < 0.001 and ****P < 0.0001. (Scale bars, 50 μm). (See also SI Appendix, Fig. S4).

Article Snippet: For experiments using VDAC1 oligomerization inhibitor (VBIT-12; Selleckchem S8936), mice were pretreated with VBIT-12 (20 mg/kg, p.o.) or vehicle (10% DMSO + 70% of PEG-400 + 20% Tween-80) 24 h prior, followed a second booster treatment 1 h prior to the first injection of caerulein.

Techniques: Isolation, Transduction, Genome Wide, Quantitative Proteomics, Expressing, Over Expression, Two Tailed Test, In Vivo, Chromatin Immunoprecipitation, ChIP-qPCR, Binding Assay, Saline, Western Blot, Injection, Activity Assay

Journal: Proceedings of the National Academy of Sciences of the United States of America

Article Title: Upregulation of the ERRγ-VDAC1 axis underlies the molecular pathogenesis of pancreatitis.

doi: 10.1073/pnas.2219644120

Figure Lengend Snippet: Fig. 5. ERRγ inhibitor is an effective experimental therapeutic in treating pancreatitis. (A) Representative IHC staining of ERRγ and VDAC1 in pancreatic tissue from patients and quantification of the samples (n = 5 subjects/group). (B) Scheme of pancreatitis induction (CER) and treatment. Pancreatitis was induced by caerulein, and therapeutic drug (DN) was administered twice, 7 and 11 h after the first caerulein injection. (C) Representative H&E images and histology scoring of the pancreas from mice in B. (D) Serum amylase level and intrapancreatic trypsin activity of mice in B. (n = 6 mice/group; two-tailed t -test) (E) Pancreatitis induction (CER) and treatment in PRSS1R122H mice. Pancreatitis was induced by caerulein, and therapeutic drug (DN) was administered 5 h after the first caerulein injection. Vehicle or DN were given twice daily (10 mg/kg; b.i.d) for the next 7 d. Representative H&E images, histology scoring and pancreas weight to body weight ratio of mice after 7 d of treatment. (n = 7 mice/group; two-tailed t test). (F) Schematic representation of the molecular regulatory role of the ERRγ–VDAC1 axis that contributes toward the pathogenesis of pancreatitis. Results are representative of those from two independent in vivo experiments. Data represent mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001. (Scale bars, 50 μm). (See also SI Appendix, Fig. S5 and Table S1).

Article Snippet: For experiments using VDAC1 oligomerization inhibitor (VBIT-12; Selleckchem S8936), mice were pretreated with VBIT-12 (20 mg/kg, p.o.) or vehicle (10% DMSO + 70% of PEG-400 + 20% Tween-80) 24 h prior, followed a second booster treatment 1 h prior to the first injection of caerulein.

Techniques: Immunohistochemistry, Injection, Activity Assay, Two Tailed Test, In Vivo