CART peptide is a potential endogenous antioxidant and preferentially localized in mitochondria.

CART peptide is a potential endogenous antioxidant and preferentially localized in mitochondria.
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DOI:
10.1371/journal.pone.0029343
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Reddy PH
Reddy PH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Mao P;Meshul CK;Thuillier P;Goldberg NR;Reddy PH

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多功能神经肽可卡因和安非他命调节转录本(CART)由下丘脑、垂体、肾上腺和胰腺分泌。它也可以在循环系统中发现。这一特征表明CART在不同细胞中的一般作用。在本研究中,我们证明了CART可以保护线粒体DNA (mtDNA)、细胞蛋白和脂质免受过氧化氢(一种广泛使用的氧化剂)的氧化作用。利用顺式parinaric酸作为敏感的膜过氧化反应探针,以及脂溶性偶氮引发过氧自由基2,2 ' -偶氮(2,4-二甲基戊腈),我们发现CART是一种抗氧化剂。此外,我们在培养细胞和小鼠脑神经细胞中发现CART定位于线粒体。更重要的是,通过全身注射CART预处理可以防止小鼠氧化应激模型,该模型模拟了帕金森病的主要特征。鉴于CART独特的分子结构和生物学特性,我们认为CART是一种抗氧化肽(或抗氧化激素)。我们进一步提出,它可能对人类疾病有很强的治疗特性,其中氧化应激强烈参与,如帕金森病。
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.
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