Linghui Song,Panpan Chen,Baimei Shi,Aihua Qu,Chuanlai Xu,Hua Kuang,Maozhong Sun
Autophagy is a key regulator in a diverse range of human diseases. Here, chiral copper sulfide (CuS) nanoparticles (NPs) modified with penicillamine are fabricated, which exhibited a circular dichroism (CD) spectrum between 300 and 1000 nm and a fluorescence peak at 680 nm. The experimental data showed that D -CuS NPs exhibited chirality-dependent autophagy induction, outperforming L -CuS NPs, and targeted breast cancer cells with 228.4 times higher affinity for CD81 receptor. The mechanism is revealed that chiral NPs specifically bound to CD81 receptor to open mechanosensitive calcium channels and motivated the calmodulin-dependent protein kinase kinase β (CaMKKβ)/AMPK pathway, which enhanced Atg1/Unc-51-like autophagy activating kinase 1 (ULK1) activity to promote autophagy. In vivo experiments confirmed the selective accumulation of D -CuS NPs in tumors, induction of autophagy, and successful treatment of the tumor. Therefore, chiral CuS NPs show great potential for modulating biological processes and improving tumor treatment.
Studies have reported attenuation of insulin resistance (IR) by improving phosphorylation of the insulin signalling pathway. However, the upstream molecular signalling pathway is still elusive. In this study, Western blot was used to evaluate the phosphorylation level of the insulin signalling pathway and the AMPK pathway. 2-NBDG was used to evaluate glucose uptake. Ca 2+ imaging was used to assess change of intracellular Ca 2+ concentration. We found that NaHS enhanced the intracellular Ca 2+ concentration and glucose uptake and activated the insulin signalling cascade in a palmitic acid (PA)-induced IR model in C2C12 cells. Furthermore, activation of the IRS1/PI3K/AKT pathway and glucose uptake were decreased when AMPK or CaMKKβ was inhibited. Our study also showed that the mitochondrial electron transport chain, ATP production, and intramitochondrial cAMP declined in the IR model but that this effect was reversed by NaHS, an effect that may be mediated by the Ca 2+ /CaMKK2/AMPK and PI3K/AKT pathways. Our data indicate that H 2 S improves activation of the insulin signalling cascade and glucose uptake via activation of the Ca 2+ /CaMKK2/AMPK pathway and mitochondrial metabolism in C2C12 cells. Furthermore, NaHS protects mitochondrial function and maintains normal ATP production by activating the cAMP system and the Ca 2+ /CaMKK2/AMPK and PI3K/ATK pathways.
危险品化学品经营许可证（带存储）