2,5-hexanedione (HD) treatment alters calmodulin, Ca2+/calmodulin-dependent protein kinase II, and protein kinase C in rats' nerve tissues.
Calcium-dependent mechanisms, particularly those mediated by Ca(2+)/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 in 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 Ca(2+) concentrations in nerve tissues. CaMKII contents and activities were also increased in CC and were positively correlated with gait abnormality, but it could not be found in SC and SN. The increases of PKC contents and activities were also observed in SN and were positively correlated with gait abnormality. Except for that of NF-M in CC, the PRs of NF-L, NF-M and NF-H were also elevated in nerve tissues, which was consistent with the activation of protein kinases. The results suggested that CaMKII might 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.
Wang
Qing-Shan
QS
Institute of Toxicology, Shandong University, 44 West Wenhua Road, Jinan 250012, PR China. wangqs1222@mail.sdu.edu.cn
Hou
Li-Yan
LY
Zhang
Cui-Li
CL
Zhao
Xiu-Lan
XL
Yu
Su-Fang
SF
Xie
Ke-Qin
KQ
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D005684:Gait / Q000187:drug effects; D020233:Gait Disorders, Neurologic / Q000139:chemically induced / Q000201:enzymology; D006588:Hexanones / Q000633:toxicity*; D007794:Lameness, Animal / Q000139:chemically induced / Q000201:enzymology; D008297:Male; D009420:Nervous System / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D016900:Neurofilament Proteins / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects / Q000201:enzymology; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology; D013997:Time Factors; D015854:Up-Regulation
D002147:Calmodulin; D006588:Hexanones; D016900:Neurofilament Proteins; C011269:2,5-hexanedione; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2