Gap 26, as a connexin mimetic peptide, which has the SHVR amino acid regions contributing crucially to the docking of connexons to generate gap junctions[1]. Gap 26 can inhibit the release of ATP induced by an increase in calcium[2]. Gap 26 inhibited electrical coupling in cell pairs mediated by gap junctions[3].
Gap 26 (25μM; 24h) attenuated the apoptosis of tubular epithelial cells[4]. Gap 26 (150μM; 24h) decreased ROS production, inhibited ASK1-JNK/p38 signaling, and decreased apoptosis in the alveolar type II epithelial cells of rats (RLE-6TN)[5].
Gap 26 (1μg/kg/day; i.p. ; 3 times a week for 8 weeks) alleviated the chronotropic hyporesponsiveness and the severity of liver damage and had an antioxidant effect on the heart in cirrhotic cardiomyopathy rats model[6]. Gap 26 (25μg/kg; i.p. ; 4 day) further deteriorated the destruction of synapses and decreased the spine density of hippocampal in middle cerebral artery occlusion (MCAO) rats model[7].
References:
[1] BOITANO S, EVANS W H. Connexin mimetic peptides reversibly inhibit Ca(2+) signaling through gap junctions in airway cells [J]. American journal of physiology Lung cellular and molecular physiology, 2000, 279(4): L623-30.
[2] BRAET K, VANDAMME W, MARTIN P E, et al. Photoliberating inositol-1,4,5-trisphosphate triggers ATP release that is blocked by the connexin mimetic peptide gap 26 [J]. Cell calcium, 2003, 33(1): 37-48.
[3] DESPLANTEZ T, VERMA V, LEYBAERT L, et al. Gap26, a connexin mimetic peptide, inhibits currents carried by connexin43 hemichannels and gap junction channels [J]. Pharmacol Res, 2012, 65(5): 546-52.
[4] TANG L, YU J, ZHUGE S, et al. Oxidative stress and Cx43-mediated apoptosis are involved in PFOS-induced nephrotoxicity [J]. Toxicology, 2022, 478(153283.
[5] QING C, XINYI Z, XUEFEI Y, et al. The Specific Connexin 43-Inhibiting Peptide Gap26 Improved Alveolar Development of Neonatal Rats With Hyperoxia Exposure [J]. Front Pharmacol, 2021, 12(587267.
[6] MOHAMMED D, TAVANGAR S M, KHODADOOSTAN A, et al. Effects of Gap 26, a Connexin 43 Inhibitor, on Cirrhotic Cardiomyopathy in Rats [J]. Cureus, 2024, 16(4): e59053.
[7] YANG K, ZHOU Y, ZHOU L, et al. Synaptic Plasticity After Focal Cerebral Ischemia Was Attenuated by Gap26 but Enhanced by GAP-134 [J]. Front Neurol, 2020, 11(888.
Gap 26，作为一种模拟连接蛋白的肽，含有对连接子对接生成间隙连接至关重要的SHVR氨基酸区域[1]。Gap 26可以抑制钙升高引起的ATP释放[2]。Gap 26能够抑制由连接蛋白43半通道和间隙连接通道所携带的电流[3]。
Gap 26（25μM；24h）可减少管状上皮细胞的凋亡[4]。Gap 26（150μM; 24h）可降低大鼠肺泡II型上皮细胞（RLE-6TN）的ROS生成，抑制ASK1-JNK/p38信号通路，减少凋亡[5]。
使用Gap 26（1μg/kg/day; i.p. ; 3 times a week for 8 weeks）处理肝硬化心肌病模型大鼠，Gap26可减轻大鼠的变时性反应低下和肝损害程度，并对心脏具有抗氧化作用[6]。使用Gap 26（25μg/kg; i.p. ; 4 day）处理MCAO（middle cerebral artery occlusion，大脑中动脉闭塞）模型大鼠，Gap 26进一步加重了大鼠脑中的突触破坏，降低了大鼠脑中海马棘密度[7]。