N-acylethanolamide metabolizing enzymes are upregulated in human neural progenitor-derived neurons exposed to sub-lethal oxidative stress.
N-acylethanolamide metabolizing enzymes are upregulated in human neural progenitor-derived neurons exposed to sub-lethal oxidative stress.
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DOI：
10.3389/fncel.2022.902278
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发表时间：
2022
影响因子：
5.3
通讯作者：
Koulen, Peter
中科院分区：
文献类型：
--
作者：
Duncan, R. Scott;Riordan, Sean M.;Hall, Conner W.;Payne, Andrew J.;Chapman, Kent D.;Koulen, Peter
n -酰基酰胺（NAAs）是一类脂质，由与氨基酸、神经递质、牛磺酸或乙醇酰胺基团（n -酰基乙醇胺或NAEs）相连的酰基组成，包括一些内源性大麻素（eCB），如anandamide。这些脂质在多种生物体和多种细胞类型中合成，包括神经元。NAEs参与许多细胞和生理过程，其浓度在缺血和物理创伤反应中升高，发挥神经保护作用。eCB NAEs的神经保护特性使这些化合物的蛋白质靶点成为各种疾病临床干预的有吸引力的靶点。其中最有希望的靶点包括大麻素受体1型（CB1）、大麻素受体2型（CB2）、脂肪酸酰胺水解酶（FAAH）、n -酰基乙醇胺酸酰胺酶（NAAA）和n -酰基磷脂酰乙醇胺磷脂酶D （NAPE-PLD）。在更现代的神经变性和神经保护模型系统中进一步表征这些靶点，将使我们能够充分描述它们在抗氧化应激神经保护中的作用和作用机制，从而在临床环境中更好地利用它们。人类干细胞衍生或人类神经祖细胞衍生的细胞，如ReN细胞，已越来越多地用于人类神经元发育和神经退行性疾病的研究。ReN细胞可以很容易地分化，从而避免了使用转化细胞系和原代神经元作为细胞模型系统的需要。在这项研究中，我们确定了ReN细胞（一种用于研究神经发育、分化和神经保护的优越细胞模型系统）是否表达与典型eCB NAE信号相关的蛋白质，以及氧化应激是否可以诱导它们的表达。我们确定亚致死氧化应激上调所有eCB蛋白的表达。此外，我们确定氧化应激增加了FAAH的核定位，并在较小程度上增加了NAAA和NAPE-PLD。这项研究是确定氧化应激如何影响CB1， CB2， FAAH， NAAA和NAPE-PLD表达及其对氧化应激的潜在防御的第一步。因此，我们的数据对于进一步确定eCB代谢蛋白和eCB受体抗氧化应激的作用很重要。
N-acyl amides (NAAs) are a class of lipids that consist of an acyl group N-linked to an amino acid, neurotransmitter, taurine or ethanolamide group (N-acylethanolamines or NAEs) and include some endocannabinoids (eCB) such as anandamide. These lipids are synthesized in a wide variety of organisms and in multiple cell types, including neurons. NAEs are involved in numerous cellular and physiological processes and their concentrations are elevated in response to ischemia and physical trauma to play a role in neuroprotection. The neuroprotective properties of eCB NAEs make the protein targets of these compounds attractive targets for clinical intervention for a variety of conditions. The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection will allow us to fully describe their role and mechanism of action in neuroprotection against oxidative stress leading to better utilization in the clinical setting. Human stem cell-derived or human neural progenitor cell-derived cells, such as ReN cells, have become more utilized for the study of human neuronal development and neurodegenerative diseases. ReN cells can be easily differentiated thereby circumventing the need for using transformed cell lines and primary neurons as cell model systems. In this study, we determined whether ReN cells, a superior cell model system for studying neurodevelopment, differentiation, and neuroprotection, express proteins involved in canonical eCB NAE signaling and whether oxidative stress can induce their expression. We determined that sublethal oxidative stress upregulates the expression of all eCB proteins tested. In addition, we determined that oxidative stress increases the nuclear localization of FAAH, and to a lesser extent, NAAA and NAPE-PLD. This study is a first step toward determining how oxidative stress affects CB1, CB2, FAAH, NAAA, and NAPE-PLD expression and their potential defense against oxidative stress. As such, our data is important for further determining the role of eCB metabolizing proteins and eCB receptors against oxidative stress.
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影响因子：
4.2
作者：
Elmazoglu Z;Rangel-López E;Medina-Campos ON;Pedraza-Chaverri J;Túnez I;Aschner M;Santamaría A;Karasu Ç
通讯作者：
Karasu Ç
影响因子：
29
作者：
Jeong, Won-il;Osei-Hyiaman, Douglas;Kunos, George
通讯作者：
Kunos, George
影响因子：
3.8
作者：
Chamley, L. W.;Bhalla, A.;Glass, M.
通讯作者：
Glass, M.
影响因子：
5.6
作者：
Aso E;Ferrer I
通讯作者：
Ferrer I
影响因子：
29.4
作者：
Julien, B;Grenard, P;Lotersztajn, S
通讯作者：
Lotersztajn, S