Influence of trimethyl lead and inorganic lead on the in vitro assembly of microtubules from mammalian brain.
The influence of trimethyl lead (TriML) and inorganic lead (Pb) on the in vitro assembly of microtubules (MTs) from tubulin of porcine brain was studied using turbidity measurements and electron microscopy. At concentrations of 150 to 650 microM Pb, no significant effects on the in vitro assembly of MTs could be detected by both methods. On the other hand, TriML increasingly blocked MT assembly at 100 to 200 microM and completely inhibited assembly at 300 microM TriML and higher concentrations. Application of 400 microM TriML to preassembled MTs caused an immediate drop of the optical density. Electron microscopy showed that one minute after addition of TriML to assembled MTs only very few intact MTs could be detected whereas ten minutes later MTs were completely absent. The observed increase of optical density following the TriML-induced drop was found to be due to the formation of clusters of aggregates but not to assembly of MTs. The results demonstrate that inorganic lead and trimethyl lead have different effects on the in vitro assembly of MTs. It is assumed that the selective neurotoxic effects of organic lead might be due, at least in part, to impairments of neurotubular structures and functions.
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000648:ultrastructure; D007854:Lead / Q000633:toxicity*; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects*; D009391:Nephelometry and Turbidimetry; D009942:Organometallic Compounds / Q000633:toxicity*; D013552:Swine; D013756:Tetraethyl Lead / Q000031:analogs & derivatives / Q000633:toxicity*
D009942:Organometallic Compounds; D013756:Tetraethyl Lead; D007854:Lead; C039474:trimethyllead