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.

Role of Mitochondria on the Neurological Effects of Cocaine

“…The peptide encoded by the cocaine and amphetamine regulated transcript (CART) is upregulated by psychostimulants, and was shown to localize in mitochondria and to have antioxidant effects (Mao, Meshul, Thuillier, Goldberg, & Reddy, 2012). Thus, cocaine may also have some indirect effects on mitochondria through upregulation of CART, which was shown to interact with succinate dehydrogenase subunit B, stimulating its activity and increasing ATP production (Mao et al, 2007).…”

Nanotoxicity-Induced Alzheimer Disease and Parkinsonism: Not Further than Diagnosis

“…The nanoparticle exposure leads to impairments in normal neurons [20,21], microglia [22] and even aggravate the process of brain pathology was reported earlier [5]. Ion channels serve a subtle indicator of the condition and viability of the cells.…”

“…by modulation of the current reading to alterations in functionality [23]. Previous studies revealed that the nanoparticles can impair cell function and even induce certain cell death [20]. Exposure of metallic nanoparticles such as Ag in a neuroendocrine cell line (PC-12 cells) induces neurotoxicity, characterized by the reduction in the level of DA.…”

Recent progress and concerns in dementia: Distinguishing Alzheimer's disease and dementia with Lewy bodies via biochemical markers in the cerebrospinal fluid

“…Recently, we reported that CART has a general cytoprotection in mammalian and human cells [12]. Using cis-parinaric acid as a sensitive reporting probe for peroxidation in membranes, and a lipid-soluble azo initiator of peroxyl radicals, we found that CART has an antioxidant property.…”

“…CART is one of the latest hormones, expressed in the nervous system and circulatory system with multiple functions. We recently found that CART is a mitochondrial booster and a novel endogenous antioxidant [11,12], suggesting its potential relationship with neurodegenerative diseases.…”