Triptolide induces p53-dependent cardiotoxicity through mitochondrial membrane permeabilization in cardiomyocytes was written by Xi, Yue;Wang, Wenwen;Wang, Li;Pan, Ji;Cheng, Yisen;Shen, Feihai;Huang, Zhiying. And the article was included in Toxicology and Applied Pharmacology in 2018.Recommanded Product: 63208-82-2 The following contents are mentioned in the article:
Triptolide (TP), a major active component of Tripterygium wilfordii Hook f., is widely used in the treatment of inflammation and autoimmune disorders. Its clin. application is limited by severe adverse effects, especially cardiotoxicity. Accumulative evidences indicate that TP induces DNA damage by inhibiting RNA polymerase. Considering the relationship among DNA damage, p53, and the role of p53 in mitochondria-dependent apoptosis, we speculate that TP-induced cardiotoxicity results from p53 activation. In this study, the role of p53 in TP-induced cardiotoxicity was investigated in H9c2 cells, primary cardiomyocytes, and C57BL/6 genetic background p53-/- mice. p53 protein level was elevated by TP in vitro and in acute heart injury models. With TP administration, p53 deficiency prevented heart histol. injury and decreased serum cardiac troponin I (cTn-I) and apoptotic proteins. Mechanistically, immunoblotting and immunofluorescence staining identified that TP-induced toxicity is dependent on p53 nuclear translocation and transactivation of Bcl2 family genes, leading to mitochondrial outer membrane permeabilization (MOMP) and mitochondria dysfunction. Consistently, p53 antagonist PFTα counteracted TP-induced p53 overexpression and regulation of Bcl2 family transcription, which improved mitochondrial membrane integrity and prevented apoptosis. These results suggest that TP-induced cardiotoxicity is p53-dependent by promoting Bax-induced mitochondria-mediated apoptosis. This study involved multiple reactions and reactants, such as 2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2Recommanded Product: 63208-82-2).
2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2) belongs to thiazole derivatives. Thiazole rings are planar and aromatic. Thiazoles are characterized by larger pi-electron delocalization than the corresponding oxazoles and have therefore greater aromaticity. Electrophilic attack at nitrogen depends on the presence of electron density at nitrogen as well as the position and nature of substituent linked to the thiazole ring.Recommanded Product: 63208-82-2
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica