Generation of a GLO-2 deficient mouse reveals its effects on liver carbonyl and glutathione levels.
Generation of a GLO-2 deficient mouse reveals its effects on liver carbonyl and glutathione levels.
复制标题
DOI：
10.1016/j.bbrep.2021.101138
复制
发表时间：
2021-12
影响因子：
2.7
通讯作者：
Wood KD
中科院分区：
文献类型：
--
作者：
Li X;Fargue S;Challa AK;Poore W;Knight J;Wood KD
羟酰基谷胱甘肽水解酶(又名GLO-2)是乙醛酶途径的一个组成部分，参与了乙二醛、乙二醛和甲基乙二醛的解毒过程。这些反应性代谢产物与多种病理情况有关，包括糖尿病、癌症和心脏病，并可能参与衰老过程。这项研究的目的是建立GLO-2缺陷的小鼠模型，以深入了解GLO-2的功能，并确定它是否可能与内源性草酸合成有关，从而影响尿中草酸的排泄。用CRISPR/CAS9技术建立了GLO-2基因敲除小鼠。在基线条件下采集成年雄性和雌性动物的组织和24小时尿样进行生化分析，包括测定乙醇酸、草酸、乙二醛、甲基乙二醛、D-乳酸、抗坏血酸和谷胱甘肽水平。GLO-2KO动物发育正常，24 h尿草酸排泄量、肝脏甲基乙二醛、乙二醛、抗坏血酸和谷胱甘肽水平及血浆d-乳酸水平均无明显变化。Glo-2缺乏的雄性比野生型雄性的血浆乙醇酸水平更低，而这种关系在雌性中没有观察到。在基线条件下，GLO-2 KO小鼠模型中缺乏独特的表型与最近的证据一致，这表明功能乙醛酶途径不是最佳健康所必需的。在雄性GLO-2 KO动物中，较低的血浆乙醇酸表明乙二醛的产生可能是循环中乙醇酸水平的重要因素，但不是内源性草酸合成的重要因素。
Hydroxyacylglutathione hydrolase (aka as GLO-2) is a component of the glyoxalase pathway involved in the detoxification of the reactive oxoaldehydes, glyoxal and methylglyoxal. These reactive metabolites have been linked to a variety of pathological conditions, including diabetes, cancer and heart disease and may be involved in the aging process. The objective of this study was to generate a mouse model deficient in GLO-2 to provide insight into the function of GLO-2 and to determine if it is potentially linked to endogenous oxalate synthesis which could influence urinary oxalate excretion. A GLO-2 knock out mouse was generated using CRISPR/Cas 9 techniques. Tissue and 24-h urine samples were collected under baseline conditions from adult male and female animals for biochemical analyses, including chromatographic measurement of glycolate, oxalate, glyoxal, methylglyoxal, D-lactate, ascorbic acid and glutathione levels. The GLO-2 KO animals developed normally and there were no changes in 24-h urinary oxalate excretion, liver levels of methylglyoxal, glyoxal, ascorbic acid and glutathione, or plasma d-lactate levels. GLO-2 deficient males had lower plasma glycolate levels than wild type males while this relationship was not observed in females. The lack of a unique phenotype in a GLO-2 KO mouse model under baseline conditions is consistent with recent evidence, suggesting a functional glyoxalase pathway is not required for optimal health. A lower plasma glycolate in male GLO-2 KO animals suggests glyoxal production may be a significant contributor to circulating glycolate levels, but not to endogenous oxalate synthesis.
登录
查看更多内容
影响因子：
6.6
作者：
Li, X;Qu, ZC;May, JM
通讯作者：
May, JM
影响因子：
5.3
作者：
Kander MC;Cui Y;Liu Z
通讯作者：
Liu Z
DOI：
10.1055/s-0030-1265145
发表时间：
2010-11
期刊：
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
影响因子：
--
作者：
Knight J;Assimos DG;Easter L;Holmes RP
通讯作者：
Holmes RP
DOI：
10.1016/j.bbadis.2019.165633
发表时间：
2020-03-01
影响因子：
6.2
作者：
Buchalski, Brianna;Wood, Kyle D.;Knight, John
通讯作者：
Knight, John
DOI：
10.1590/s0100-879x2002000900008
发表时间：
2002-09-01
影响因子：
2.3
作者：
Barp, J.;Araújo, A.S.R.;Singal, P.
通讯作者：
Singal, P.