cPKCβ-mediated phosphorylation inhibits CRMP2 proteolysis and alleviates ischemic injury in cultured cortical neurons and ischemic stroke-induced mice

Journal of Neurochemistry
Xuan YangJunfa Li

Abstract

We previously reported that conventional protein kinase C (cPKC)β participated in hypoxic preconditioning (HPC)-induced neuroprotection against cerebral ischemic injury, and collapsin response-mediated protein 2 (CRMP2) was identified as a cPKCβ-interacting protein. In this study, we explored the regulation of CRMP2 phosphorylation and proteolysis by cPKCβ, and their role in ischemic injury of oxygen-glucose deprivation (OGD)-treated cortical neurons and brains of mice with middle cerebral artery occlusion (MCAO)-induced ischemic stroke. The results demonstrated that cPKCβ-mediated CRMP2 phosphorylation via the cPKCβ-selective activator DOPPA and inhibition of calpain-mediated CRMP2 proteolysis by calpeptin and TAT-CRMP2 protected neurons against OGD induced cell death through inhibiting CRMP2 proteolysis in cultured cortical neurons. The OGD-induced nuclear translocation of the CRMP2 breakdown product (BDP) was inhibited by DOPPA, calpeptin and TAT-CRMP2 in cortical neurons. In addition, both cPKCβ activation and CRMP2 proteolysis inhibition by HPC and intracerebroventricular injections of DOPPA, calpeptin and TAT-CRMP2 improved the neurological deficit in addition to reducing the infarct volume and proportions of cells with p...Continue Reading

References

Jan 1, 1989·Stroke; a Journal of Cerebral Circulation·E Z LongaR Cummins
May 22, 1998·Stroke; a Journal of Cerebral Circulation·S AshwalW J Pearce
Mar 29, 2001·Neuroscience Research·V V Zakharov, M I Mosevitsky
Jul 31, 2001·Nature Neuroscience·N InagakiK Kaibuchi
Aug 18, 2001·Journal of Applied Physiology·G W Lu, H Y Liu
Aug 17, 2002·The Journal of Pharmacology and Experimental Therapeutics·Rodney P GuttmannDavid R Lynch
Nov 5, 2003·Journal of Neurobiology·Nariko ArimuraKozo Kaibuchi
Jun 3, 2004·The Journal of Clinical Investigation·Tomoyuki FujitaShi-Fang Yan
Nov 2, 2005·Molecular and Cellular Biology·Nariko ArimuraKozo Kaibuchi
Jan 18, 2006·Biochemical and Biophysical Research Communications·Candice Ginn T TahimicAkihiro Kurimasa
May 23, 2006·Nature Reviews. Neuroscience·Jeffrey M Gidday
Jun 22, 2006·Journal of Neurochemistry·Sylvie BretinChristian Gauchy
Aug 4, 2007·The European Journal of Neuroscience·Susan X JiangSheng T Hou
Feb 5, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Linghua KongShi-Fang Yan
Mar 12, 2008·The Journal of Biological Chemistry·Véronique RogemondMahnaz Moradi-Améli
Aug 8, 2008·Molecular Neurobiology·P S VoslerJ Chen
Jun 28, 2011·Mitochondrion·Joanna E KowalczykBarbara Zabłocka
Feb 3, 2012·Neurobiology of Disease·Shadia E Nada, Zahoor A Shah
Feb 4, 2012·Journal of Neuroscience Research·Kazuo Kitagawa

❮ Previous
Next ❯

Citations

Sep 7, 2016·International Journal of Molecular Sciences·Nan ZhangJunfa Li
Apr 27, 2019·Frontiers in Pharmacology·Fawad Ali ShahPhil-Ok Koh
Sep 23, 2021·Molecular Neurobiology·Sandeep AppunniVishnu Swarup

❮ Previous
Next ❯

Related Concepts

Related Feeds

Acute Stroke

A stroke occurs when blood supply to the brain is interrupted depriving the brain of oxygen and nutrients. This feed focuses cerebrovascular accidents including ischemic and paralytic stroke.

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.