NF-κB/mTOR-mediated autophagy can regulate diquat-induced apoptosis was written by Park, Aeri;Koh, Hyun Chul. And the article was included in Archives of Toxicology in 2019.Formula: C16H19BrN2OS The following contents are mentioned in the article:
Autophagy and apoptosis are the major types of cell death in pesticide-induced neurotoxicity, and autophagy is known to play a role in cell protection by inhibiting apoptosis. In this study, we characterized the relationship between autophagy and apoptosis in diquat (DQ)-induced cell death and explored a novel pharmacotherapeutic approach involving autophagy regulation to prevent DQ neurotoxicity. DQ was cytotoxic to PC12 cells in a concentration-dependent manner, as shown by decreased cell viability and decreased dopamine (DA) levels. DQ-induced apoptosis was found in PC12 cells, as demonstrated by activation of caspase-3 and -9 and by nuclear condensation. By monitoring expression of microtubule-associated protein 1A/1B light chain 3B (LC3-II) and p62, DQ was found to induce autophagy. Exposure of PC12 cells to DQ led to the production of reactive oxygen species (ROS), and N-acetyl-cysteine (NAC) antioxidant effectively blocked both apoptosis and autophagy. Interestingly, DQ in PC12 cells showed increased p53 and NF- κB in a time-dependent manner; furthermore, pifithrin- α (PFT- α), a p53 inhibitor, downregulates the cytotoxicity of DQ, as shown by decreased LC3-II and cleaved caspase-3. SN50, an NF- κB inhibitor, results in diminished LC3-II, cleaved caspase-3, and p53. DQ induces mitogen-activated protein kinase (MAPK) signaling including ERK, JNK, and p38, which inhibit regulated apoptosis and autophagic cell death by controlling mTOR signaling. In addition, modulation of DQ-induced apoptosis in response to autophagy regulation was investigated. Pretreatment with rapamycin, an autophagy inducer, significantly enhanced the viability of DQ-exposed cells by alleviating DQ-induced apoptosis. Conversely, cell pretreatment with 3-methyladenine (3MA), an autophagy inhibitor increased DQ toxicity. Our results suggest that DQ-induced cytotoxicity is modified by autophagy regulation. Pharmacol. induction of autophagy may be a useful treatment strategy in neurodegenerative disorders. This study involved multiple reactions and reactants, such as 2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2Formula: C16H19BrN2OS).
2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2) belongs to thiazole derivatives. Thiazoles frequently appear in peptide studies. Thiazoles can also be used as protected formyl groups, which can be released in later stages of complex natural product synthesis. The pyridine-type nitrogen in the thiazole ring deactivates the ring for electrophilic substitution reactions, which is further reduced in acid due to protonation of the thiazole ring.Formula: C16H19BrN2OS
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica