Protein kinase Calpha and beta1 isoforms are regulators of alpha-secretory proteolytic processing of amyloid precursor protein in vivo

The European Journal of Neuroscience
S RossnerV Bigl

Abstract

We have recently shown that in utero treatment of guinea pigs with the DNA methylating substance methylazoxymethanol acetate (MAM) results in neocortical microencephalopathy, increased protein kinase C (PKC) activity and altered processing of the amyloid precursor protein (APP) in neocortex of offspring. Here we show that PKCalpha and PKCbeta1 are the key regulators of alpha-secretory APP processing in guinea pig neocortex under these experimental conditions in vivo. This conclusion is based on the selective translocation of PKCalpha and PKCbeta1 isoforms to the cell membrane in MAM-treated guinea pigs, as revealed by Western blot analysis and by immunocytochemistry. Additionally, we observed that [3H]phorbol ester binding to protein kinase C increased by 38% and enhanced basal PKC activity by 58% in the neocortex of microencephalic guinea pigs. Inhibition of PKCalpha/PKCbeta1 by Gö6976 abolished this difference, suggesting that constitutive overactivation of these PKC isoforms accounts for the increase in total PKC activity. We also observed a strong positive correlation between levels of alpha-secretase-processed APP and PKC activity in the neocortex of individual animals, providing further evidence for a significant role of ...Continue Reading

References

Mar 15, 1989·Biochemical and Biophysical Research Communications·E KobayashiT Tamaoki
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·S LammichF Fahrenholz

❮ Previous
Next ❯

Citations

May 5, 2001·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·S RossnerV Bigl
Feb 9, 2010·Antioxidants & Redox Signaling·Carlotta GiorgiPaolo Pinton
Apr 20, 2004·Neuroreport·Hyeon-Jin KimSeong-Tshool Hong
Jul 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·René EtcheberrigarayDaniel L Alkon
Jun 17, 2003·Journal of Neurochemistry·Faina Kuperstein, Ephraim Yavin
Oct 6, 2012·Biochimica Et Biophysica Acta·Jing ShiXuemin Xu
Sep 17, 2011·Journal of Proteomics·Elena Bonzon-KulichenkoJesús Vázquez
Jan 19, 2005·Journal of Pharmacological Sciences·Ana OlariuToshitaka Nabeshima
Jun 24, 2018·International Journal of Molecular Sciences·Sindhu RameshMuralikrishnan Dhanasekaran
Jun 8, 2018·Frontiers in Neuroinformatics·Javaria AshrafZaheer Ul-Haq
Nov 14, 2019·International Journal of Molecular Sciences·Thomas Ho-Yin LeeSuk-Yu Yau
Jan 2, 2008·Journal of Proteome Research·Jon M JacobsBrian D Thrall

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.