RRC ID 59742
著者 Migita K, Matsumoto T, Terada K, Ono K, Hara S.
タイトル Effects of geldanamycin on neurite outgrowth-related proteins and kinases in nerve growth factor-differentiated pheochromocytoma 12 cells.
ジャーナル J Pharmacol Sci
Abstract Heat shock protein 90 (HSP90) antagonists are currently being evaluated as potential anticancer drugs. However, adverse effects related to these drugs, such as fatigue and pain, suggest that they affect neurons. Therefore, to understand the influence of HSP90 inhibitors on neurons, we investigated the effects of geldanamycin, an HSP90 antagonist, on nerve growth factor (NGF)-differentiated pheochromocytoma 12 (PC12) cells, particularly, on the expression and phosphorylation of proteins and kinases in the NGF pathway. Geldanamycin significantly inhibited NGF-induced neurite outgrowth and phosphorylation of Akt and extracellular signal-related kinase 1/2 in PC12 cells. Furthermore, geldanamycin inhibited the phosphorylation of collapsin response mediator protein 2 and the expression of cyclin-dependent kinase 5 in the presence of NGF, but did not significantly affect the expression of glycogen synthase kinase 3β. These results suggest that geldanamycin influences microtubule-binding proteins and kinases relating to neurite outgrowth, thereby inducing neuronal impairment.
巻・号 140(3)
ページ 255-262
公開日 2019-7-1
DOI 10.1016/j.jphs.2019.07.011
PII S1347-8613(19)35691-9
PMID 31402210
MeSH Adrenal Gland Neoplasms / drug therapy* Adrenal Gland Neoplasms / metabolism Animals Benzoquinones / pharmacology* Cell Differentiation / drug effects* Cell Line, Tumor Extracellular Signal-Regulated MAP Kinases / metabolism Glycogen Synthase Kinase 3 beta / metabolism Intercellular Signaling Peptides and Proteins / metabolism Lactams, Macrocyclic / pharmacology* Nerve Growth Factor / metabolism* Nerve Tissue Proteins / metabolism Neurites / drug effects* Neurites / metabolism Neuronal Outgrowth / drug effects* Neurons / drug effects Neurons / metabolism PC12 Cells Pheochromocytoma / drug therapy* Pheochromocytoma / metabolism Phosphorylation / drug effects Rats Signal Transduction / drug effects
IF 2.835
引用数 0
リソース情報
ヒト・動物細胞 PC-12(RCB0009)