Time-dependent alteration of cytoskeletal proteins in cerebral cortex of rat during 2,5-hexanedione-induced neuropathy.
To investigate the mechanisms of the axonopathy induced by 2,5-hexanedione (2,5-HD), male Wistar rats were administered at a dosage of 400 mg/kg/day 2,5-HD (five times per week). The rats produced a slightly, moderately, or severely abnormal neurological changes, respectively, after 2, 4, or 8 weeks of treatment. The cerebrums were Triton-extracted and ultracentrifuged to yield a pellet fraction and a corresponding supernatant fraction. The relative levels of six cytoskeletal proteins (NF-L, NF-M, NF-H, alpha-tubulin, beta-tubulin, and beta-actin) in both fractions were determined by immunoblotting. The results showed that NFs content in HD-treated rats demonstrated a progressive decline as the intoxication of HD continued. As for microtubule proteins, the levels of alpha-tubulin and beta-tubulin demonstrated some inconsistent changes. The content of alpha-tubulin kept unchangeable, while the content of beta-tubulin increased significantly at the late stage of HD exposure. Furthermore, the content of beta-actin in both fractions remained unaffected throughout the study. These findings suggest that HD intoxication resulted in a progressive decline of NFs, which was highly correlated with the development of HD-induced neuropathy.
Song
Fuyong
F
Institute of Toxicology, Shandong University, 44 West Wenhua Road, Jinan, Shandong, People's Republic of China.
Zhang
Cuili
C
Yu
Sufang
S
Zhao
Xiulan
X
Yu
Lihua
L
Xie
Keqin
K
D000818:Animals; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006588:Hexanones / Q000494:pharmacology / Q000633:toxicity*; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced / Q000473:pathology; D009498:Neurotoxins / Q000494:pharmacology / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D003598:Cytoskeletal Proteins; D006588:Hexanones; D009498:Neurotoxins; C011269:2,5-hexanedione