5-Hydroxydecanoate sodium is a selective ATP-sensitive K+ (KATP) channel blocker with an IC50 value of 28.7μM [1]. 5-Hydroxydecanoate sodium can traverse the mitochondrial inner membrane and acts as a substrate for mitochondrial outer membrane acyl-CoA synthetase, with the activity of inhibiting both ischaemic and pharmacological preconditioning [2]. 5-Hydroxydecanoate sodium has been widely used to alter mitochondrial membrane potential and inhibit the proliferation of hypoxic human pulmonary artery smooth muscle cells (hPASMCs)[3].
In vitro, 5-Hydroxydecanoate sodium treatment (10μM) for 24 hours inhibited the toxicity of 6-hydroxydopamine (6-OHDA) to isolated dopaminergic neurons and blocked the decrease in mitochondrial membrane potential induced by 6-OHDA[4]. Pre-treatment with 100μM 5-Hydroxydecanoate sodium for 30 minutes significantly abolished the inhibitory effect of Penehyclidine hydrochloride (PHC) on the cell damage in H9c2 cells induced by anoxia/reoxygenation (A/R), promoted Ca2+ overload and ROS generation, and facilitated the release of cytochrome C from mitochondria into the cytoplasm[5]. Treatment with 100μM 5-Hydroxydecanoate sodium for 20 minutes can weaken the protective effect of puerarin (Pue) in the isolated cardiomyocyte ischemia model and promote cell death[6].
In vivo, injecting 5-Hydroxydecanoate sodium (10mg/kg) and paclitaxel (4.5mg/kg) intraperitoneally every other day for a week enabled the mice to regain the thermal sensitivity and alleviate mechanical allodynia[7]. Two intraperitoneal injections of 5-Hydroxydecanoate sodium (5mg/kg) were administered weekly for 12 weeks, which aggravated the atherosclerotic degree and pro-inflammatory response in ApoE−/− mice fed with a high-fat diet[8].
References:
[1] Li X, Rapedius M, Baukrowitz T, et al. 5-Hydroxydecanoate and coenzyme A are inhibitors of native sarcolemmal KATP channels in inside-out patches[J]. Biochimica et Biophysica Acta (BBA)-General Subjects, 2010, 1800(3): 385-391.
[2] Hanley P J, Gopalan K V, Lareau R A, et al. β‐Oxidation of 5‐hydroxydecanoate, a Putative Blocker of Mitochondrial ATP‐Sensitive Potassium Channels[J]. The Journal of physiology, 2003, 547(2): 387-393.
[3] Wang T, ZHANG Z, XU Y, et al. 5‐Hydroxydecanoate inhibits proliferation of hypoxic human pulmonary artery smooth muscle cells by blocking mitochondrial KATP channels 1[J]. Acta Pharmacologica Sinica, 2007, 28(10): 1531-1540.
[4] Rodriguez-Pallares J, Parga J A, Joglar B, et al. The mitochondrial ATP-sensitive potassium channel blocker 5-hydroxydecanoate inhibits toxicity of 6-hydroxydopamine on dopaminergic neurons[J]. Neurotoxicity research, 2009, 15(1): 82-95.
[5] Zi C, Zhang C, Yang Y, et al. Penehyclidine hydrochloride protects against anoxia/reoxygenation injury in cardiomyocytes through ATP‐sensitive potassium channels, and the Akt/GSK‐3β and Akt/mTOR signaling pathways[J]. Cell Biology International, 2020, 44(6): 1353-1362.
[6] Gao Q, Pan H Y, Qiu S, et al. Atractyloside and 5-hydroxydecanoate block the protective effect of puerarin in isolated rat heart[J]. Life sciences, 2006, 79(3): 217-224.
[7] Chen L H, Sun Y T, Chen Y F, et al. Integrating image-based high-content screening with mouse models identifies 5-hydroxydecanoate as a neuroprotective drug for paclitaxel-induced neuropathy[J]. Molecular cancer therapeutics, 2015, 14(10): 2206-2214.
[8] Zhang Y, Ding X, Yuan C, et al. Anti-Inflammatory Responses Produced with Nippostrongylus brasiliensis-Derived Uridine via the Mitochondrial ATP-Sensitive Potassium Channel and Its Anti-Atherosclerosis Effect in an Apolipoprotein E Gene Knockout Mouse Model[J]. Biomolecules, 2024, 14(6): 672.
5-Hydroxydecanoate sodium是一种选择性的ATP敏感性钾（KATP）通道阻滞剂，IC50值为28.7μM[1]。5-Hydroxydecanoate sodium可穿过线粒体内膜，作为线粒体外膜酰辅酶A合成酶的底物，具有抑制缺血性和药理性预适应的活性[2]。5-Hydroxydecanoate sodium已被广泛用于改变线粒体膜电位并抑制缺氧状态下人肺动脉平滑肌细胞(hPASMCs)的增殖[3]。
在体外，使用10μM的5-Hydroxydecanoate sodium处理24小时，抑制了6-羟基多巴胺（6-OHDA）对分离的多巴胺能神经元的毒性，并阻断了6-OHDA诱导的线粒体膜电位下降[4]。用100μM的5-Hydroxydecanoate sodium预处理30分钟，显著消除了Penehyclidine hydrochloride (PHC)对缺氧/复氧（A/R）诱导的H9c2细胞损伤的抑制作用，促进了Ca2+超载和ROS生成，并促进了细胞色素C从线粒体释放到细胞质[5]。使用100μM的5-Hydroxydecanoate sodium处理20分钟，可削弱puerarin (Pue)在离体心肌细胞缺血模型中的保护作用，并促进细胞死亡 [4]。
在体内，每隔一天腹腔注射5-Hydroxydecanoate sodium（10mg/kg）和紫杉醇（4.5mg/kg），持续一周，使小鼠恢复了热敏感性并减轻了机械性痛觉超敏[7]。每周两次腹腔注射5-Hydroxydecanoate sodium（5mg/kg），持续12周，加剧了高脂饮食喂养的ApoE−/−小鼠的动脉粥样硬化程度和促炎反应[8]。