2,5-hexanedione (HD) treatment alters calmodulin, Ca2+/calmodulin-dependent protein kinase II, and protein kinase C in rats' nerve tissues

作者：Wang, Qing-Shan; Hou, Li-Yan; Zhang, Cui-Li; Zhao, Xiu-Lan; Yu, Su-Fang; Me, Ke-Qin^*

来源：Toxicology and Applied Pharmacology, 2008, 232(1): 60-68.

DOI：10.1016/j.taap.2008.05.021

• Neuropathy
• Ca2+
• caMKII
• PKC
• Polymerization ratio

Calcium-dependent mechanisms, particularly those mediated by Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII). have been implicated in neurotoxicant-induced neuropathy. However, it is unknown whether similar mechanisms exist in 2,5-hexanedione (HD)-induced neuropathy. For that, we investigated the changes of CaM, CaMKII, protein kinase C (PKC) and polymerization ratios (PRs) of NF-L, NF-M and NF-H ill cerebral cortex (CC, including total cortex and some gray), spinal cord (SC) and sciatic nerve (SN) of rats treated with HD at a dosage of 1.75 or 3.50 mmol/kg for 8 weeks (five times per week). The results showed that CaM contents in CC, SC and SN were significantly increased, which indicated elevation of Ca2+ concentrations in nerve tissues. CaMKII contents and activities were also increased in CC and were positively correlated with all abnormality. but it Could not be found in SC and SN. The increases of PKC contents and were also observed in SN and were positively correlated With gait abnormality. Except for that of act NF-M in CC, the I1Rs of NF-L, NFM and NF-H were also elevated in nerve (issues, which was consistent with the activation of protein kinases. The results Suggested that CaMKII ought be partly (in CC but not in SC and SN) involved in HD-induced neuropathy. CaMKII and PKC might mediate the HD neurotoxicity by altering the NF phosphorylation Status and PRs.

• 出版日期2008-10-1
• 单位山东大学; 中国医学科学院北京协和医院; 国家卫生计生委科学技术研究所