title: cAMP stimulates the ubiquitin/proteasome pathway in rat spinal cord neurons.
abstract: Proteasome impairment and accumulation of ubiquitinated proteins are implicated in neurodegeneration associated with different forms of spinal cord injury. We show herein that elevating cAMP in rat spinal cord neurons increases 26S proteasome activity in a protein kinase A-dependent manner. Treating spinal cord neurons with dibutyryl-cAMP (db-cAMP) also raised the levels of various components of the UPP including proteasome subunits Rpt6 and β5, polyubiquitin shuttling factor p62/sequestosome1, E3 ligase CHIP, AAA-ATPase p97 and the ubiquitin gene ubB. Finally, db-cAMP reduced the accumulation of ubiquitinated proteins, proteasome inhibition, and neurotoxicity triggered by the endogenous product of inflammation prostaglandin J2. We propose that optimizing the effects of cAMP/PKA-signaling on the UPP could offer an effective therapeutic approach to prevent UPP-related proteotoxicity in spinal cord neurons.
authors.affiliation: Department of Biological Sciences, Hunter College and Graduate Center, CUNY, New York, NY 10065, USA.
authors.forename: Natura
authors.initials: N
authors.lastname: Myeku
authors.forename: Hu
authors.initials: H
authors.lastname: Wang
authors.forename: Maria E
authors.initials: ME
authors.lastname: Figueiredo-Pereira
mesh_terms: D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D025801:Ubiquitin / Q000502:physiology*
chemical_list: D025801:Ubiquitin; C037112:9-deoxy-delta-9-prostaglandin D2; D003994:Bucladesine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D015230:Prostaglandin D2