LVV-H7在酒精诱导的奖励机制中的作用

IF 2.6 3区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Przemyslaw Mielczarek, Kinga Hartman, Eagle Yi-Kung Huang, Ewa Gibula-Tarlowska, Pawel Grochecki, Tymoteusz Slowik, Jolanta H. Kotlinska, Jerzy Silberring, Anna Drabik
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引用次数: 0

摘要

本研究旨在探讨左室-血红素-7 (LVV-H7)在酒精依赖中的作用。LVV-H7是一种由血红蛋白链裂解产生的短肽,与阿片受体结合,在各种生理和病理过程中发挥多种作用。此外,LVV-H7在酒精的存在下被更高浓度的劈裂。我们在动物模型中进行了行为实验,并对酒精成瘾大鼠的中枢神经系统组织进行了蛋白质组学分析,以确定LVV-H7的结合伙伴。利用荧光显微镜,我们证实了合成的LVV-H7及其释放酶抑制剂胃抑素的血脑屏障(BBB)通透性。我们的研究结果揭示了LVV-H7数量与酒精水平之间的剂量依赖性相关性。基于质谱的分析确定了LVV-H7在成瘾大鼠中枢神经系统组织中的蛋白结合靶点以及负责其降解的酶。这些发现强调了LVV-H7在酒精依赖机制中的重要作用,并表明了hemorphin作为治疗靶点的潜在作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The Role of LVV-H7 in Alcohol-Induced Reward Mechanisms

The Role of LVV-H7 in Alcohol-Induced Reward Mechanisms

This study aimed to investigate the role of LVV-hemorphin-7 (LVV-H7) in alcohol dependence. LVV-H7 is a short peptide derived from the cleavage of haemoglobin chains that binds to opioid receptors and plays diverse roles in various physiological and pathological processes. Additionally, LVV-H7 is cleaved at higher concentrations in the presence of alcohol. We conducted behavioural experiments in animal models and performed proteomic analyses of CNS tissues from alcohol-addicted rats to identify LVV-H7 binding partners. Using fluorescent microscopy, we confirmed the blood–brain barrier (BBB) permeability of synthesized LVV-H7 and its releasing enzyme inhibitor, pepstatin. Our results revealed a dose-dependent correlation between LVV-H7 quantities and alcohol levels. Mass spectrometry-based analyses identified LVV-H7's protein-binding targets in CNS tissues of addicted rats and the enzymes responsible for their degradation. These findings highlight the significant role of LVV-H7 in the mechanisms underlying alcohol dependence and indicate the potential role of hemorphin as a therapeutic target.

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来源期刊
Addiction Biology
Addiction Biology 生物-生化与分子生物学
CiteScore
8.10
自引率
2.90%
发文量
118
审稿时长
6-12 weeks
期刊介绍: Addiction Biology is focused on neuroscience contributions and it aims to advance our understanding of the action of drugs of abuse and addictive processes. Papers are accepted in both animal experimentation or clinical research. The content is geared towards behavioral, molecular, genetic, biochemical, neuro-biological and pharmacology aspects of these fields. Addiction Biology includes peer-reviewed original research reports and reviews. Addiction Biology is published on behalf of the Society for the Study of Addiction to Alcohol and other Drugs (SSA). Members of the Society for the Study of Addiction receive the Journal as part of their annual membership subscription.
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