Increased synthesis of membrane macromolecules is an early response of retinal neurons to trimethyltin intoxication.
We studied the synthesis and axonal transport of proteins and glycoproteins in the visual system of adult Long-Evans rats that had received 4 weekly doses of trimethyltin hydroxide (TMT, 4 mg/kg b. wt.) by gastric intubation. One week following the last dose, an in vitro assay was used to study the rate of incorporation of radioactive precursors into various macromolecules of isolated retinas. Retinas from TMT-treated rats showed increased apparent rates of synthesis, relative to retinas from control rats, for proteins [( 35S]methionine precursor) and glycoproteins [( 3H]fucose precursor). Gel electrophoretic analysis of newly synthesized proteins indicated that the increased synthesis was a generalized effect, i.e. it was not restricted to a select subset of proteins. The axonal transport of these macromolecules by retinal ganglion cells to axons (optic tract) and nerve endings (superior colliculus) was examined in vivo following intraocular precursor injection. The amount of material transported, relative to that synthesized in the retina, was not appreciably altered in TMT-treated rats, indicating that TMT did not selectively impair axonal transport. The biochemical changes were accompanied by minimal ultrastructural alterations and little neuronal necrosis in the retina. We suggest that TMT induces increased synthesis of membrane macromolecules in retinal neurons; this may reflect an early reactive (compensatory) response rather than a regressive (degenerative) response of retinal neurons to TMT. Our data do not support the hypothesis that TMT induces a functional impairment of neuronal endoplasmic reticulum or Golgi apparatus.
D000818:Animals; D001370:Axonal Transport; D005136:Eye Proteins / Q000096:biosynthesis*; D005260:Female; D005643:Fucose / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis*; D008297:Male; D008715:Methionine / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051381:Rats; D012160:Retina / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism; D013477:Superior Colliculi / Q000378:metabolism; D014220:Trialkyltin Compounds / Q000633:toxicity*; D014298:Trimethyltin Compounds / Q000633:toxicity*
D005136:Eye Proteins; D006023:Glycoproteins; D014220:Trialkyltin Compounds; D014298:Trimethyltin Compounds; C037718:trimethyltin hydroxide; D005643:Fucose; D008715:Methionine