S-（2-琥珀酰）半胱氨酸 (2SC) 的组织分布，肥胖和糖尿病线粒体应激的生物标志物。,Obesity

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S-（2-琥珀酰）半胱氨酸 (2SC) 的组织分布，肥胖和糖尿病线粒体应激的生物标志物。
Obesity ( IF 4.2 ) Pub Date : 2011-12-01 , DOI: 10.1038/oby.2011.340
Sonia A Thomas ₁ , Kenneth B Storey , John W Baynes , Norma Frizzell

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S-(2-succino)cysteine (2SC) 是一种蛋白质的化学修饰，通过富马酸盐与蛋白质中的硫醇基团反应产生，这一过程称为琥珀化。从现在开始，我们建议使用名称 S-(2-succinyl)cysteine（而不是 S-(2-succinyl)cysteine）。这是为了区分蛋白质琥珀化（其中富马酸盐与半胱氨酸残基形成硫醚键）与琥珀酰化（其中将形成酯、硫酯或酰胺键）。1 型糖尿病大鼠的肌肉和 2 型糖尿病小鼠的脂肪组织中蛋白质的琥珀化增加。2SC 的增加是富马酸盐组织积累的直接结果，以应对糖尿病中营养过剩和由此产生的线粒体应激。在这项研究中，我们检查了 db/db 2 型糖尿病模型中组织蛋白的琥珀化广度。我们还确定了 1 型（秋田、链脲佐菌素 (STZ)）和 2 型（ob/ob、db/db）糖尿病小鼠、饮食诱导肥胖 (DIO) 小鼠和脂肪细胞中的琥珀化程度。地松鼠在不同冬眠阶段的组织。虽然在 db/db 糖尿病模型中的大多数组织（脑、心脏、肾脏、肝脏、骨骼肌）中琥珀化没有增加，但与对照组相比，2 型糖尿病和 DIO 小鼠的所有脂肪层中都增加了。1 型糖尿病小鼠的脂肪细胞中的琥珀化没有增加。还研究了来自冬眠 (HIB) 13 内衬地松鼠的脂肪组织，以确定在没有高血糖的情况下肥胖是否会影响蛋白质的琥珀化。在整个麻木-觉醒周期中，棕色或白色脂肪组织中蛋白质的琥珀化没有差异。

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Tissue distribution of S-(2-succino)cysteine (2SC), a biomarker of mitochondrial stress in obesity and diabetes.

S-(2-succino)cysteine (2SC) is a chemical modification of proteins produced by reaction of fumarate with thiol groups in protein, a process known as succination. We propose to use the name S-(2-succino)cysteine (instead of S-(2-succinyl)cysteine) from this point on. This is to distinguish protein succination (in which fumarate forms a thioether linkage with cysteine residues) from succinylation (in which an ester, thioester or amide bond would be formed). Succination of proteins is increased in muscle of type 1 diabetic rats and in adipose tissue in type 2 diabetic mice. The increase in 2SC is a direct result of tissue accumulation of fumarate in response to nutrient excess and resultant mitochondrial stress in diabetes. In this study, we examine the breadth of succination of tissue proteins in the db/db type 2 model of diabetes. We also determined the extent of succination in epididymal adipocytes of type 1 (Akita, streptozotocin (STZ)) and type 2 (ob/ob, db/db) diabetic mice, in diet-induced obese (DIO) mice, and in the adipose tissue of ground squirrels in various stages of hibernation. While succination was not increased in most tissues (brain, heart, kidney, liver, skeletal muscle) in the db/db model of diabetes, it was increased in all adipose beds of type 2 diabetic and DIO mice in comparison to their controls. Succination was not increased in adipocytes of type 1 diabetic mice. Adipose tissue from hibernating (HIB) 13-lined ground squirrels was also studied to determine if obesity in the absence of hyperglycemia affected succination of proteins. There were no differences in succination of proteins in brown or white adipose tissue over the torpor-arousal cycle. We conclude that 2SC is a biomarker of nutrient excess and mitochondrial stress in adipose tissue, increasing under the hyperglycemic and insulin resistant conditions associated with type 2 diabetes and obesity.

更新日期：2019-11-01

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