Effect of miR-132 on bupivacaine-induced neurotoxicity in human neuroblastoma cell line
JOURNAL OF PHARMACOLOGICAL SCIENCES
Authors: Zhang, Huiying; Lin, Jianzhong; Hu, Tingting; Ren, Zhiyun; Wang, Weiwan; He, Qiyue
Abstract
Background: Local anesthetics (LAs) may generate neurotoxicity in neurons. In the current study, we explored the mechanisms by which microRNA-132 (miR-132) regulated the neurotoxicity of human neuroblastoma cells (SH-SY5Y) induced by bupivacaine (BUP). Methods: CCK-8, flow cytometry, EdU detection, qRT-PCR and western blotting were used to explore the cell viability, apoptosis and gene expression, respectively. Results: In this study, we found that 600 mM BUP dramatically inhibited SH-SY5Y cells viability. In addition, BUP induced cell apoptosis and neurotoxicity via increasing active caspase-3 and cleaved PARP1 levels. More importantly, the level of miR-132 was significantly up-regulated in BUP-treated cells, which was significantly reversed by miR-132 inhibitor. In addition, dual-luciferase assay indicated IGF1R was the directly binding target of miR-132 in cells. Our study further indicated that the level of IGF1R was markedly decreased by BUP interference, while miR-132 inhibitor exerted the opposite effect. Furthermore, BUP induced apoptosis and neurotoxicity in SH-SY5Y cells were attenuated by IGF1, which further confirmed IGF1R was the downstream target of BUP in SH-SY5Y cells. Conclusion: In the present study, miR-132 played important roles in regulating BUP-induced neurotoxicity through IGF1R and may act as a promising molecular target for the treatment of human neurotoxicity induced by BUP. (c) 2019 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Comparative Insilco physiochemical and phylogenetic analysis of insulin like growth factor 1 receptor (IGF-1R) in domestic animals
INDIAN JOURNAL OF ANIMAL RESEARCH
Authors: Sahoo, P. R.; Sahoo, G.; Behera, P. C.
Abstract
Insulin like growth factor 1 receptors (IGF-1R) are the proteins which are expressed on the cell surface of almost all tissues in human as well as domestic animals with major involvement in growth, cancer, aging, production and in early embryonic development. Due to above importance, this protein needs to be characterized both in physiochemical and phylogenetically for further exploration in livestock research. In this study, the IGF1R amino acid sequences of selected domestic animals are retrieved from UniProt database and various physiochemical parameters were compared through Prot Param insilco tool. The multiple sequence alignment (MSA) and phylogenetic analysis was performed through Clustal omega and Molecular evolutionary genetics analysis (MEGA) application platform respectively. It was found that this protein is an unstable, hydrophilic in all domestic animals with amino acids varied from 1307 to 1412 in number. The phylogenetic analysis showed that highest time of divergence occurs in killer whale and rabbit, but least time of divergence occurs between goat and bovine. So this study will provide a better platform for the development of suitable anticancer therapeutics in domestic animals in nearest future as IGF-1R is implicated in several cancers, including breast, prostate and lung cancers.