Changes of cytoskeletal proteins in nerve tissues and serum of rats treated with 2,5-hexanedione.
To investigate the mechanisms and biomarker of the neuropathy induced by 2,5-hexanedione (HD), male Wistar rats were administrated HD at dosage of 200 or 400mg/kg for 8 weeks (five-times per week). All rats were sacrificed after 8 weeks of treatment and the cerebrum cortex (CC), spinal cord (SC) and sciatic nerves (SN) were dissected, homogenized and used for the determination of cytoskeletal proteins by western blotting. The levels of neurofilaments (NFs) subunits (NF-L, NF-M and NF-H) in nerve tissues of 200 and 400mg/kg HD rats significantly decreased in both the supernatant and pellet fractions. Furthermore, significant negative correlations between NFs levels and gait abnormality were observed. As for microtubule (MT) and microfilament (MF) proteins, the levels of alpha-tubulin, beta-tubulin and beta-actin in the supernatant and pellet fraction of SN significantly decreased in 200 and 400mg/kg HD rats and correlated negatively with gait abnormality. However, the contents of MT and MF proteins in CC and SC were inconsistently affected and had no significant correlation with gait abnormality. The levels of NF-L and NF-H in serum significantly increased, while NF-M, alpha-tubulin, beta-tubulin and beta-actin contents remain unchanged. A significant positive correlation (R=0.9427, P<0.01) was observed between gait abnormality and NF-H level in serum as the intoxication went on. These findings suggested that HD intoxication resulted in a progressive decline of cytoskeletal protein contents, which might be relevant to the mechanisms of HD-induced neuropathy. NF-H was the most sensitive index, which may serve as a good indicator for neurotoxicity of n-hexane or HD.
Wang
Qing-Shan
QS
Institute of Toxicology, Shandong University, 44 West Wenhua Road, Jinan 250012, PR China.
Hou
Li-Yan
LY
Zhang
Cui-Li
CL
Song
Fu-Yong
FY
Xie
Ke-Qin
KQ
D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006588:Hexanones / Q000633:toxicity*; D007794:Lameness, Animal / Q000139:chemically induced / Q000523:psychology; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008868:Microtubule Proteins / Q000378:metabolism; D009417:Nerve Tissue / Q000737:chemistry / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000737:chemistry / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000523:psychology; D009498:Neurotoxins / Q000633:toxicity*; D011092:Polyethylene Glycols; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism; D012997:Solvents; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
D000199:Actins; D015415:Biomarkers; D003598:Cytoskeletal Proteins; D006588:Hexanones; D008840:Microfilament Proteins; D008868:Microtubule Proteins; D016900:Neurofilament Proteins; D009498:Neurotoxins; D012997:Solvents; D014404:Tubulin; D011092:Polyethylene Glycols; C011269:2,5-hexanedione