TCEP hydrochloride is a non-thiol reducing agent which does not bind Hg(2+).[1] TCEP hydrochloride increased SOD1 monomer formation, thus preventing the NO‐induced increase in dismutase activity and the decrease in ROS.[5]
In vitro efficacy test it shown that TCEP hydrochloride promoted NF-kappaB-DNA binding in a dose-related manner in concentrations from 0.25 to 6mM. with 6mM TCEP hydrochloride , Hg(2+) prevented NF-kappaB-DNA binding at concentrations as low as 20 microM in binding reactions.[1]
In vitro experiment it indicated that treatment with 100 μM TCEP hydrochloride-HCL can improve the quality and developmental capacity of in vitro-fertilized embryos by decreasing oxidative stress in porcine oocytes.[2] In human neuronal cell line, SHSY-5Y, with 1 mM TCEP hydrochloride maximally protected against BoNT/B inhibition of [(3)H]-NA release, and has no toxic.[3] TCEP hydrochloride (0.01 mM) does not scavenge Fe(3+) from Tf and is able to protect thiol groups for the coupling to maleimide. In addition, TCEP hydrochloride does not interfere with the maleimide coupling itself.[4] In vitro, human hepatocellular (HepG2) cells were treated with 100, 200, and 400 μM TCEP hydrochloride for 3 days, the level of oxidative stress, esterase, Ca2+ influx, and ΔΨm dysfunction increased. And there were 65.96% subG1 apoptotic peak in 400 μM treated cells.[6]
In vivo, treatment with 20 mg/kg and 60 mg/kg TCEP hydrochloride orally in adult ICR mice for 9 weeks, TCEP improved body weight gain, hypertriglyceridemia, and hepatic steatosis, consistent with upregulation of hepatic lipogenesis-related gene expression. TCEP also altered the levels of several hepatic metabolites.[7]
References:
[1].Dieguez-Acu?a FJ, et al. Inhibition of NF-kappaB-DNA binding by mercuric ion: utility of the non-thiol reductant, tris(2-carboxyethyl)phosphine hydrochloride (TCEP hydrochloride), on detection of impaired NF-kappaB-DNA binding by thiol-directed agents. Toxicol In Vitro. 2000 Feb;14(1):7-16.
[2]Zeng Y, et al. Effects of tris (2-carboxyethyl) phosphine hydrochloride treatment on porcine oocyte in?vitro maturation and subsequent in?vitro fertilized embryo developmental capacity. Theriogenology. 2021 Mar 1;162:32-41.
[3]Shi X, et al. TCEP hydrochloride treatment reduces proteolytic activity of BoNT/B in human neuronal SHSY-5Y cells. J Cell Biochem. 2009 Aug 1;107(5):1021-30.
[4]Visser CC, et al. Coupling of metal containing homing devices to liposomes via a maleimide linker: use of TCEP to stabilize thiol-groups without scavenging metals. J Drug Target. 2004;12(9-10):569-73.
[5]Peng H, et al. Nitric oxide inhibits endothelial cell apoptosis by inhibiting cysteine-dependent SOD1 monomerization. FEBS Open Bio. 2022 Feb;12(2):538-548.
[6]M Al-Salem A, et al. Tris(2-chloroethyl) Phosphate (TCEP) Elicits Hepatotoxicity by Activating Human Cancer Pathway Genes in HepG2 Cells. Toxics. 2020 Nov 20;8(4):109.
[7]Yang D, et al. Tris (2-chloroethyl) phosphate (TCEP) induces obesity and hepatic steatosis via FXR-mediated lipid accumulation in mice: Long-term exposure as a potential risk for metabolic diseases. Chem Biol Interact. 2022 Aug 25;363:110027.
TCEP hydrochloride 是一种不结合 Hg(2+) 的非硫醇还原剂。[1] TCEP hydrochloride 增加了 SOD1 单体的形成，从而阻止了 NO 诱导的歧化酶活性增加和ROS 减少。[5]
体外功效测试表明，TCEP hydrochloride 在 0.25 至 6mM 浓度范围内以剂量相关的方式促进 NF-kappaB-DNA 结合。使用 6mM TCEP 盐酸盐，Hg(2+) 在结合反应中以低至 20 microM 的浓度阻止 NF-kappaB-DNA 结合。[1]
体外实验表明，用 100 μM TCEP 盐酸盐-HCL 处理可以通过降低猪卵母细胞的氧化应激来提高体外受精胚胎的质量和发育能力。[2] 在人类中神经元细胞系 SHSY-5Y，含 1 mM TCEP 盐酸盐，最大限度地防止 BoNT/B 抑制 [(3)H]-NA 释放，并且没有毒性。[3] TCEP 盐酸盐 (0.01 mM) 不会从 Tf 中清除 Fe(3+)，并且能够保护硫醇基团以与马来酰亚胺偶联。此外，TCEP 盐酸盐不会干扰马来酰亚胺偶联本身。[4] 在体外，人肝细胞 (HepG2) 分别用 100、200 和 400 μM TCEP 盐酸盐处理 3 天，氧化应激水平、酯酶、Ca2+ 内流和 δψm 功能障碍增加。并且在400 μM处理的细胞中有65.96%的subG1凋亡峰。[6]
在体内，成年 ICR 小鼠口服 20 mg/kg 和 60 mg/kg TCEP 盐酸盐治疗 9 周后，TCEP 改善了体重增加、高甘油三酯血症和肝脂肪变性，这与肝脂肪生成相关基因表达的上调一致. TCEP 还改变了几种肝脏代谢物的水平。[7]