Neuroprotection via pro-survival protein kinase C isoforms associated with Bcl-2 family members

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Orly WeinrebMoussa B H Youdim

Abstract

This study provides new insights into neuroprotection involving interaction of protein kinase C (PKC) pathway with Bcl-2 family proteins. Using a model of serum deprivation, we investigated the mechanism by which the anti-Parkinson/monoamine oxidase (MAO)-B inhibitor drug, rasagiline, exerts its neuroprotective effect in rat pheochromocytoma PC12 cells. Here, we report that rasagiline (0.1-10 microM) decreased apoptosis via multiple protection mechanisms, including the stimulation of PKC phosphorylation; up-regulation of PKCalpha and PKC mRNAs, induction of Bcl-xL, Bcl-w, and brain-derived neurotrophic factor (BDNF) mRNAs; and down-regulation of Bad and Bax mRNAs. Moreover, rasagiline inhibited the cleavage and activation of procaspase-3 and poly (ADP-ribose) polymerase (PARP), whereas the PKC inhibitor, GF109203X, reversed these actions. Similarly, rasagiline decreased serum-free-induced levels of the important regulator of cell death, Bad, which was also blocked by GF109203X, indicating the involvement of PKC in rasagiline-induced cell survival. Furthermore, these studies have established that PKC- and Bcl-2-dependent neuroprotective activity of rasagiline is dependent on its propargyl moiety, because propargylamine had simil...Continue Reading

References

Oct 1, 1993·The American Journal of Physiology·A KribbenR A Nemenoff
Jan 22, 1998·Biochemical and Biophysical Research Communications·W C KuT C Wang
Aug 28, 1998·Science·G Evan, T Littlewood
Sep 12, 1998·Science·J M Adams, S Cory
Nov 27, 1999·The Journal of Biological Chemistry·Y TanM J Comb
Jan 29, 2000·FEBS Letters·Y Tsujimoto, S Shimizu
May 16, 2000·Journal of Neural Transmission·K A Jellinger
Oct 26, 2000·Nature·J Yuan, B A Yankner
Nov 21, 2000·American Journal of Surgery·R MaruyamaH Anai
Nov 22, 2000·Journal of Biochemical and Biophysical Methods·T D Schmittgen, B A Zakrajsek
Jul 21, 2001·Annals of the New York Academy of Sciences·W MaruyamaM Naoi
Sep 19, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Merav Yogev-FalachMoussa B H Youdim
Sep 5, 2002·Nature Reviews. Cancer·Suzanne Cory, Jerry M Adams
Dec 21, 2002·Archives of Neurology·UNKNOWN Parkinson Study Group
Mar 11, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Orly WeinrebMoussa B H Youdim
Apr 19, 2003·British Journal of Clinical Pharmacology·A K Mantel-TeeuwisseA de Boer
Oct 4, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Merav Yogev-FalachMoussa B H Youdim
Nov 1, 2003·Expert Review of Neurotherapeutics·Moussa Bh Youdim

❮ Previous
Next ❯

Citations

Nov 11, 2010·Naunyn-Schmiedeberg's Archives of Pharmacology·Ying PengXiaoliang Wang
Mar 2, 2011·Journal of Neural Transmission·Jean C ShihKevin Chen
Dec 27, 2008·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Orly WeinrebMoussa B H Youdim
Jan 24, 2013·Translational Psychiatry·L ManterolaJ L Zugaza
Apr 1, 2008·The Journal of Biological Chemistry·Rayudu GopalakrishnaThomas H McNeill
Jun 15, 2011·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Katherine FormanJ A F Tresguerres
Jul 18, 2012·Neuropsychiatric Disease and Treatment·Kathryn D Gaines, Vanessa K Hinson
Feb 15, 2011·Pharmacology, Biochemistry, and Behavior·Alvin V TerryScott J Webster
Jul 6, 2010·Progress in Neurobiology·Orly WeinrebMoussa B H Youdim
Mar 6, 2016·Progress in Neuro-psychopharmacology & Biological Psychiatry·Zdeněk Fišar
Dec 24, 2008·Brain Research·Sarah EliashMoshe Rehavi
Jun 24, 2008·Experimental Neurology·Anthony H V Schapira
Jun 28, 2008·Progress in Neurobiology·André Toulouse, Aideen M Sullivan
Jan 29, 2008·Experimental Neurology·Nadia StefanovaGregor K Wenning
Feb 14, 2007·The American Journal of Geriatric Pharmacotherapy·David R P Guay
May 5, 2010·CNS Neuroscience & Therapeutics·Zsigmond Tamas Kincses, Laszlo Vecsei
Feb 18, 2011·British Journal of Pharmacology·Offir ErtrachtOfer Binah
Sep 29, 2011·Movement Disorders : Official Journal of the Movement Disorder Society·Peter Jenner, J William Langston
Jun 29, 2011·Psychogeriatrics : the Official Journal of the Japanese Psychogeriatric Society·Kiyoko KatoMasatoshi Takeda
Jul 5, 2008·Chemico-biological Interactions·Orly WeinrebMoussa B H Youdim
Jan 5, 2005·Trends in Pharmacological Sciences·Moussa B H Youdim, Jerry J Buccafusco

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis