title: CART peptide is a potential endogenous antioxidant and preferentially localized in mitochondria.
abstract: The multifunctional neuropeptide Cocaine and Amphetamine Regulated Transcript (CART) is secreted from hypothalamus, pituitary, adrenal gland and pancreas. It also can be found in circulatory system. This feature suggests a general role for CART in different cells. In the present study, we demonstrate that CART protects mitochondrial DNA (mtDNA), cellular proteins and lipids against the oxidative action of hydrogen peroxide, a widely used oxidant. Using cis-parinaric acid as a sensitive reporting probe for peroxidation in membranes, and a lipid-soluble azo initiator of peroxyl radicals, 2,2'-azobis(2,4-dimethylvaleronitrile) we found that CART is an antioxidant. Furthermore, we found that CART localized to mitochondria in cultured cells and mouse brain neuronal cells. More importantly, pretreatment with CART by systemic injection protects against a mouse oxidative stress model, which mimics the main features of Parkinson's disease. Given the unique molecular structure and biological features of CART, we conclude that CART is an antioxidant peptide (or antioxidant hormone). We further propose that it may have strong therapeutic properties for human diseases in which oxidative stress is strongly involved such as Parkinson's disease.
authors.affiliation: The Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America. maop@ohsu.edu
authors.forename: Peizhong
authors.initials: P
authors.lastname: Mao
authors.forename: Charles K
authors.initials: CK
authors.lastname: Meshul
authors.forename: Philippe
authors.initials: P
authors.lastname: Thuillier
authors.forename: Natalie R S
authors.initials: NR
authors.lastname: Goldberg
authors.forename: P Hemachandra
authors.initials: PH
authors.lastname: Reddy
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology; D018384:Oxidative Stress; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D000975:Antioxidants; D004272:DNA, Mitochondrial; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein