Diabetic neuropathy: inhibitory G protein dysfunction involves PKC-dependent phosphorylation of Goα
Article first published online: 7 JUL 2003
Journal of Neurochemistry
Volume 86, Issue 4, pages 1006–1014, August 2003
How to Cite
Shangguan, Y., Hall, K. E., Neubig, R. R. and Wiley, J. W. (2003), Diabetic neuropathy: inhibitory G protein dysfunction involves PKC-dependent phosphorylation of Goα. Journal of Neurochemistry, 86: 1006–1014. doi: 10.1046/j.1471-4159.2003.01912.x
- Issue published online: 21 JUL 2003
- Article first published online: 7 JUL 2003
- Received February 21, 2003; revised manuscript received May 7, 2003; accepted May 13, 2003.
- diabetes mellitus;
- diabetic neuropathy;
- G protein;
We examined the hypothesis that decreased inhibitory G protein function in diabetic neuropathy is associated with increased protein kinase C (PKC)-dependent phosphorylation of the Goα subunit. Streptozotocin-induced diabetic rats were studied between 4 and 8 weeks after onset of diabetes and compared with aged-matched healthy animals as controls. Opioid-mediated inhibition of forskolin-stimulated cyclic AMP was significantly less in dorsal root ganglia (DRGs) from diabetic rats compared with controls. Activation of PKC in DRGs from control rats was associated with a significant decrease in opioid-mediated inhibition of forskolin-stimulated cyclic AMP that was similar to the decrease in inhibition observed in DRGs from diabetic rats. Both basal and PKC-mediated labeling of Goα with 32Pi was significantly less in DRGs from diabetic rats, supporting increased endogenous PKC-dependent phosphorylation of Goα. Probing of immunoprecipitated Goα with an anti-phospho-serine/threonine specific antibody revealed a significant increase in baseline phosphorylation in diabetic DRGs. Activation of PKC produced a significant increase in phosphorylation in control DRGs but no significant increase in Goα in diabetic DRGs. Phosphorylation of PKC-α was increased, PKC-βII was unchanged and PKC-δ decreased in diabetic DRGs. These results suggest that diminished inhibitory G protein function observed in DRGs neurons from diabetic rats involves an isoform-specific PKC-dependent pathway.