Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.4.4 (kinesin)
 5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

2,5-Hexanedione (2,5-HD) exposure in rats causes a progressive Sertoli cell injury culminating in testicular atrophy. Morphological injury is preceded by alterations in the assembly characteristics of tubulin isolated from exposed rat testes. This is followed by decreased seminiferous tubule fluid (STF) secretion by Sertoli cells and an increase in the number and size of Sertoli cell vacuoles. The possible involvement of microtubules and microtubule motor-dependent transport processes in STF secretion by Sertoli cells prompted us to examine the immunodistribution of the microtubule motors cytoplasmic dynein and kinesin during and after 2,5-HD exposure in rats. Three weeks following the commencement of exposure (1% 2,5-HD in the drinking water), the intensity of apical Sertoli cell cytoplasmic dynein immunofluorescence declined. This staining deficit became statistically significant by 4 weeks of exposure. Accompanying this change, there was progressive disruption of the immunodistribution of cisternal Golgi elements and associated kinesin immunoreactivity. The decrease in apical Sertoli cell cytoplasmic dynein immunofluorescence and disruption of Golgi and kinesin immunoreactivity suggest that 2,5-HD-induced alterations in Sertoli cell-mediated transport and secretory events could involve deficits in microtubule-dependent motor function.
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PMID:2,5-Hexanedione exposure alters microtubule motor distribution in adult rat testis. 773 29

Microtubules treated with the gamma-diketone 2,5-hexanedione (2,5-HD) have altered assembly behavior characterized by precocious nucleation and rapid elongation. By measuring the rate of microtubule transport, we have examined the potential functional significance of this 2,5-HD-induced microtubule modification. 2,5-HD-treated microtubules were transported at only 70% of the rate of control microtubules in a simple kinesin-based motility assay on glass coverslips using video and computer enhanced differential interference contrast microscopy. Since 2,5-HD is capable of forming both pyrrole adducts and crosslinks with tubulin, the contributions of pyrrole formation and crosslinking to slowed microtubule transport were determined. 3-Acetyl-2,5-hexanedione (AcHD), a pyrrole forming, non-crosslinking congener of 2,5-HD which does not alter microtubule assembly, did not produce slowed microtubule transport as occurs with 2,5-HD. However, glutaraldehyde, a pyrrole-independent crosslinking agent which alters microtubule assembly in the same way as 2,5-HD, slowed microtubule transport. These results indicate that a 2,5-HD-induced microtubule modification, possibly a crosslink-related conformational change, produces both an alteration in the kinetics of assembly and an alteration in the microtubule-motor interaction.
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PMID:Microtubules with altered assembly kinetics have a decreased rate of kinesin-based transport. 819 12

Exposure to occupational and environmental toxicants can result in distal axonopathies through reaction with various components of the axonal cytoskeleton. The solvents n-hexane and methyl n-butyl ketone are metabolized to the beta-diketone, 2,5-hexanedione, which covalently cross-links neurofilaments, resulting in large paranodal axonal swellings filled with neurofilaments. Carbon disulfide exposure leads to an identical axonopathy, achieving neurofilament cross-linking through a parallel series of reactions. Acrylamide and ethylene oxide, on the other hand, adduct proteins but do not lead to cross-linking. These toxicants appear to affect the function of microtubule-associated proteins, such as kinesin, and result in the impaired transport of synaptic vesicles.
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PMID:Neurotoxicants and the cytoskeleton. 1067 57