Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.4.4 (
kinesin
)
5,033
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Acrylamide (ACR) is an environmental toxicant and prototypic tool for studying mechanisms of peripheral neuropathies. Reductions in fast anterograde axonal transport (faAXT) are thought to be a critical step leading to axonal degeneration. Kinesin and microtubules (MT) were evaluated as molecular sites of action using an in vitro MT motility assay. The number of locomoting MT which lifted from a bed of
kinesin
(MT detachments or
MTD
), increased from 7% in controls to 80, 89, and 100% following preincubation of
kinesin
(37 degrees C, 20 min) with 0.1, 0.5, or 1.0 mM ACR, respectively; rates were variably reduced by as much as 20%. Similar alterations were observed with N-ethylmaleimide. A non-neurotoxic analogue, propionamide (1mM), had no effect on either parameter. Preincubation of taxol-stabilized MT with ACR produced a dose-dependent increase in
MTD
but no changes in rate. We conclude that
kinesin
and MT are covalently modified by ACR resulting in reduced affinity for each other. The greater sensitivity of
kinesin
indicates that a primary cause of transient, ACR-induced reductions in faAXT is covalent modification of
kinesin
. Such reductions in faAXT may be sufficient to produce axonal degeneration. Further, ACR may prove useful as a pharmacological tool to decipher the complex mechanics of
kinesin
-MT interactions.
...
PMID:Direct effect of the neurotoxicant acrylamide on kinesin-based microtubule motility. 889
