Okadaic acid reversibly inhibits neurite outgrowth in embryonic dorsal root ganglion neurons.
The aim of this study was to assess the effects of low concentrations of okadaic acid (OA) on neurite outgrowth and cellular integrity in cultures of dissociated dorsal root ganglion (DRG) neurons. The complete and fully reversible arrest of neurite outgrowth was achieved at 1 nM OA, thus ruling out the involvement of protein phosphatase 1 in the observed inhibitory effect. OA at 0.5 nM did not completely block neurite outgrowth, although it reduced the rate of growth by about one third. Protein phosphorylation and the integrity of microtubules and neurofilaments in neuron-enriched cultures were unaffected by 1 nM OA. The rate of synthesis of the low-molecular-weight neurofilament subunit (NFL) was also unchanged by OA treatment. Antimitotic agents used to eliminate proliferating cells did not alter the rate of neurite elongation. Since 1 nM OA does not suffice to inhibit neuronal protein phosphatase 2A fully, owing to the high concentration of this enzyme in neurons, we propose that the inhibitor is affecting a neuronal compartment that contains low levels of the phosphatase. This putative compartment is likely to be located in neurites, which were shown to contain levels of protein phosphatase 2A that were two- to threefold lower than in neuronal perikarya.
Giasson
B I
BI
McGill University, Department of Biochemistry, Montreal, Quebec, Canada.
Mushynski
W E
WE
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured / Q000187:drug effects; D005727:Ganglia, Spinal / Q000187:drug effects*; D019319:Okadaic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019319:Okadaic Acid