VBIT-12 is a unique inhibitory protein for VDAC1 [1]. VBIT-12 induces VDAC1 binding, inhibits and promotes decay protein interaction, and inhibits granular membrane voltage potential and decreases cellular pigment C release, leading to anti-decay action [2]. VBIT-12 is commonly used to treat inflammation and cardiovascular diseases [3-4].
In colon cells, VBIT-12 (10µM, 20µM; 48h) treatment of cultured colon cells inhibit DSS-induced VDAC1 overexpression, oligomerization, and apoptosis [5]. In murine hepatocytes, VBIT-12 (20µM; 2h) protects mitochondria and alleviates APAP-induced ferroptosis [6]. In R28 retinal neuron-like cells, VBIT-12 (40µM; 2h) inhibits OGD/R-induced mitochondrial damage and attenuates cell death [7].
In SOD1G93A transgenic mice, receiving intraperitoneal injection of VBIT-12 (13mg/kg, 26mg/kg; ip; 12 weeks) maintained limb muscle strength for a longer period of time [8]. In 5×FAD transgenic mice, VBIT-12 (20mg/kg; po; 5 months) inhibits cognitive decline in mice [9]. In the caerulein hyperstimulation-induced pancreatitis mice model (CER), prophylactic administration of VBIT-12 (20mg/kg; po; 24h) attenuated pancreatic histological damage, significantly reduced VDAC1 oligomerization, and decreased serum amylase levels and pancreatic trypsin activity [10].
References:
[1]. Shoshan-Barmatz V, Nahon-Crystal E, Shteinfer-Kuzmine A, et al. VDAC1, mitochondrial dysfunction, and Alzheimer's disease. Pharmacological research. 2018 May 1; 131: 87-101.
[2]. Magri A, Cubisino SA, Battiato G, et al. VDAC1 knockout affects mitochondrial oxygen consumption triggering a rearrangement of ETC by impacting on complex I activity. International Journal of Molecular Sciences. 2023 Feb 12; 24(4): 3687.
[3]. Shoshan-Barmatz V, Anand U, Nahon-Crystal E, et al. Adverse effects of metformin from diabetes to COVID-19, cancer, neurodegenerative diseases, and aging: is VDAC1 a common target?. Frontiers in physiology. 2021 Oct 4; 12: 730048.
[4]. Song JQ, Shen LJ, Wang HJ, et al. Discovery of Balasubramide Derivative with Tissue‐Specific Anti‐Inflammatory Activity Against Acute Lung Injury by Targeting VDAC1. Advanced Science. 2024 Dec;11(48): 2410550.
[5]. Verma A, Pittala S, Alhozeel B, et al. The role of the mitochondrial protein VDAC1 in inflammatory bowel disease: a potential therapeutic target. Molecular Therapy. 2022 Feb 2; 30(2): 726-744.
[6]. Niu B, Lei X, Xu Q, et al. Protecting mitochondria via inhibiting VDAC1 oligomerization alleviates ferroptosis in acetaminophen-induced acute liver injury. Cell biology and toxicology. 2022 Jun 1: 1-26.
[7]. Wan H, Yan YD, Hu XM, et al. Inhibition of mitochondrial VDAC1 oligomerization alleviates apoptosis and necroptosis of retinal neurons following OGD/R injury. Annals of Anatomy-Anatomischer Anzeiger. 2023 Apr 1; 247: 152049.
[8]. Shteinfer-Kuzmine A, Argueti-Ostrovsky S, Leyton-Jaimes MF, et al. Targeting the mitochondrial protein VDAC1 as a potential therapeutic strategy in ALS. International Journal of Molecular Sciences. 2022 Sep 1; 23(17): 9946.
[9]. Verma A, Shteinfer-Kuzmine A, Kamenetsky N, et al. Targeting the overexpressed mitochondrial protein VDAC1 in a mouse model of Alzheimer’s disease protects against mitochondrial dysfunction and mitigates brain pathology. Translational Neurodegeneration. 2022 Dec 28; 11(1): 58.
[10]. Chanda D, Thoudam T, Sinam IS, et al. Upregulation of the ERRγ–VDAC1 axis underlies the molecular pathogenesis of pancreatitis. Proceedings of the National Academy of Sciences. 2023 May 16; 120(20): e2219644120.
VBIT-12是一种独特的VDAC1抑制蛋白 [1]。VBIT-12诱导VDAC1结合，抑制并促进衰变蛋白相互作用，抑制颗粒膜电位并减少细胞色素C释放，从而发挥抗衰变作用 [2]。VBIT-12常用于治疗炎症和心血管疾病 [3-4]。
在结肠细胞中，VBIT-12（10µM、20µM；48h）处理培养的结肠细胞可抑制DSS诱导的VDAC1过表达、寡聚化和细胞凋亡 [5]。在小鼠肝细胞中，VBIT-12（20µM；2h）可保护线粒体并减轻APAP诱导的铁死亡 [6]。在R28视网膜类神经元细胞中，VBIT-12（40µM；2h）可抑制OGD/R诱导的线粒体损伤并减轻细胞死亡 [7]。
在SOD1G93A转基因小鼠中，腹膜内注射VBIT-12（13mg/kg，26mg/kg；ip；12周）可维持较长时间的肢体肌肉强度 [8]。在5×FAD转基因小鼠中，VBIT-12（20mg/kg；po；5个月）可抑制小鼠的认知能力下降 [9]。在青霉素过度刺激诱发的胰腺炎小鼠模型（CER）中，预防性给予VBIT-12（20mg/kg；po；24h）可减轻胰腺组织学损伤，显著降低VDAC1寡聚化，并降低血清淀粉酶水平和胰腺胰蛋白酶活性 [10]。