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Insulin-like growth factor-1 attenuates apoptosis and protects neurochemical phenotypes of dorsal root ganglion neurons with paclitaxel-induced neurotoxicity in vitro.
Nutr Neurosci. 2017 Feb; 20(2):89-102.NN

Abstract

Paclitaxel (PT)-induced neurotoxicity is a significant problem associated with successful treatment of cancers. Insulin-like growth factor-1 (IGF-1) is a neurotrophic factor and plays an important role in promoting axonal growth from dorsal root ganglion (DRG) neurons. Whether IGF-1 has protective effects on neurite growth, cell viability, neuronal apoptosis and neuronal phenotypes in DRG neurons with PT-induced neurotoxicity is still unclear. In this study, primary cultured rat DRG neurons were used to assess the effects of IGF-1 on DRG neurons with PT-induced neurotoxicity. The results showed that PT exposure caused neurite retraction in a dose-dependent manner. PT exposure caused a decrease of cell viability and an increase in the ratio of apoptotic cells which could be reversed by IGF-1. The percentage of calcitonin gene-related peptide immunoreactive (CGRP-IR) neurons and neurofilament (NF)-200-IR neurons, mRNA, and protein levels of CGRP and NF-200 decreased significantly after treatment with PT. IGF-1 administration had protective effects on CGRP-IR neurons, but not on NF-200-IR neurons. Either extracellular signal-regulated protein kinase (ERK1/2) inhibitor PD98059 or phosphatidylinositol 3-kinase (PI3 K) inhibitor LY294002 blocked the effect of IGF-1. The results imply that IGF-1 may attenuate apoptosis to improve neuronal cell viability and promote neurite growth of DRG neurons with PT-induced neurotoxicity. Moreover, these results support an important neuroprotective role of exogenous IGF-1 on distinct subpopulations of DRG neurons which is responsible for skin sensation. The effects of IGF-1 might be through ERK1/2 or PI3 K/Akt signaling pathways. These findings provide experimental evidence for IGF-1 administration to alleviate neurotoxicity of distinct subpopulations of DRG neurons induced by PT.

Authors+Show Affiliations

a Department of Anatomy , Shandong University School of Medicine , Jinan , Shandong Province , China.a Department of Anatomy , Shandong University School of Medicine , Jinan , Shandong Province , China.b Department of Cardiosurgery , Shandong University Qilu Hospital , Jinan , Shandong Province , China.c Department of Histology and Embryology , Binzhou Medical College , Binzhou , China.d Department of Orthopaedics , Shandong University Qilu Hospital , Jinan , Shandong Province , China.a Department of Anatomy , Shandong University School of Medicine , Jinan , Shandong Province , China.e Department of Rheumatology , Shandong University Qilu Hospital , Jinan , Shandong Province , China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25136768

Citation

Chen, Cheng, et al. "Insulin-like Growth Factor-1 Attenuates Apoptosis and Protects Neurochemical Phenotypes of Dorsal Root Ganglion Neurons With Paclitaxel-induced Neurotoxicity in Vitro." Nutritional Neuroscience, vol. 20, no. 2, 2017, pp. 89-102.
Chen C, Bai X, Bi Y, et al. Insulin-like growth factor-1 attenuates apoptosis and protects neurochemical phenotypes of dorsal root ganglion neurons with paclitaxel-induced neurotoxicity in vitro. Nutr Neurosci. 2017;20(2):89-102.
Chen, C., Bai, X., Bi, Y., Liu, G., Li, H., Liu, Z., & Liu, H. (2017). Insulin-like growth factor-1 attenuates apoptosis and protects neurochemical phenotypes of dorsal root ganglion neurons with paclitaxel-induced neurotoxicity in vitro. Nutritional Neuroscience, 20(2), 89-102. https://doi.org/10.1179/1476830514Y.0000000147
Chen C, et al. Insulin-like Growth Factor-1 Attenuates Apoptosis and Protects Neurochemical Phenotypes of Dorsal Root Ganglion Neurons With Paclitaxel-induced Neurotoxicity in Vitro. Nutr Neurosci. 2017;20(2):89-102. PubMed PMID: 25136768.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insulin-like growth factor-1 attenuates apoptosis and protects neurochemical phenotypes of dorsal root ganglion neurons with paclitaxel-induced neurotoxicity in vitro. AU - Chen,Cheng, AU - Bai,Xue, AU - Bi,Yanwen, AU - Liu,Guixiang, AU - Li,Hao, AU - Liu,Zhen, AU - Liu,Huaxiang, Y1 - 2016/03/02/ PY - 2014/8/20/pubmed PY - 2017/3/14/medline PY - 2014/8/20/entrez KW - Apoptosis KW - Calcitonin gene-related peptide KW - Dorsal root ganglion KW - Insulin-like growth factor-1 KW - Neurofilament-200 KW - Paclitaxel SP - 89 EP - 102 JF - Nutritional neuroscience JO - Nutr Neurosci VL - 20 IS - 2 N2 - Paclitaxel (PT)-induced neurotoxicity is a significant problem associated with successful treatment of cancers. Insulin-like growth factor-1 (IGF-1) is a neurotrophic factor and plays an important role in promoting axonal growth from dorsal root ganglion (DRG) neurons. Whether IGF-1 has protective effects on neurite growth, cell viability, neuronal apoptosis and neuronal phenotypes in DRG neurons with PT-induced neurotoxicity is still unclear. In this study, primary cultured rat DRG neurons were used to assess the effects of IGF-1 on DRG neurons with PT-induced neurotoxicity. The results showed that PT exposure caused neurite retraction in a dose-dependent manner. PT exposure caused a decrease of cell viability and an increase in the ratio of apoptotic cells which could be reversed by IGF-1. The percentage of calcitonin gene-related peptide immunoreactive (CGRP-IR) neurons and neurofilament (NF)-200-IR neurons, mRNA, and protein levels of CGRP and NF-200 decreased significantly after treatment with PT. IGF-1 administration had protective effects on CGRP-IR neurons, but not on NF-200-IR neurons. Either extracellular signal-regulated protein kinase (ERK1/2) inhibitor PD98059 or phosphatidylinositol 3-kinase (PI3 K) inhibitor LY294002 blocked the effect of IGF-1. The results imply that IGF-1 may attenuate apoptosis to improve neuronal cell viability and promote neurite growth of DRG neurons with PT-induced neurotoxicity. Moreover, these results support an important neuroprotective role of exogenous IGF-1 on distinct subpopulations of DRG neurons which is responsible for skin sensation. The effects of IGF-1 might be through ERK1/2 or PI3 K/Akt signaling pathways. These findings provide experimental evidence for IGF-1 administration to alleviate neurotoxicity of distinct subpopulations of DRG neurons induced by PT. SN - 1476-8305 UR - https://www.unboundmedicine.com/medline/citation/25136768/Insulin_like_growth_factor_1_attenuates_apoptosis_and_protects_neurochemical_phenotypes_of_dorsal_root_ganglion_neurons_with_paclitaxel_induced_neurotoxicity_in_vitro_ L2 - http://www.tandfonline.com/doi/full/10.1179/1476830514Y.0000000147 DB - PRIME DP - Unbound Medicine ER -