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中华老年骨科与康复电子杂志 ›› 2022, Vol. 08 ›› Issue (02) : 123 -128. doi: 10.3877/cma.j.issn.2096-0263.2022.02.009

综述

γ-谷氨酰转肽酶在骨质破坏相关疾病中的研究进展
毛燕, 师绍敏, 王旭, 胡焕荣, 刘亚玲()   
  1. 050051 石家庄,河北医科大学第三医院皮肤整形科
  • 收稿日期:2022-04-07 出版日期:2022-04-05
  • 通信作者: 刘亚玲

Advances in research of Gamma-glutamyl transpeptidase and bone destruction related diseases

Yan Mao, Shaomin Shi, Xu Wang, Huanrong Hu, Yaling Liu()   

  1. The Third Hospital of Hebei Medical University, Shijia Zhuang 050000, China
  • Received:2022-04-07 Published:2022-04-05
  • Corresponding author: Yaling Liu
引用本文:

毛燕, 师绍敏, 王旭, 胡焕荣, 刘亚玲. γ-谷氨酰转肽酶在骨质破坏相关疾病中的研究进展[J]. 中华老年骨科与康复电子杂志, 2022, 08(02): 123-128.

Yan Mao, Shaomin Shi, Xu Wang, Huanrong Hu, Yaling Liu. Advances in research of Gamma-glutamyl transpeptidase and bone destruction related diseases[J]. Chinese Journal of Geriatric Orthopaedics and Rehabilitation(Electronic Edition), 2022, 08(02): 123-128.

γ-谷氨酰转肽酶(GGT)是谷胱甘肽代谢过程中的重要酶类。多年来,GGT最常用于肝胆疾病的诊断或治疗评价。研究表明,GGT的酶活性是调节细胞及其周围环境氧化还原平衡的关键因素。GGT催化GSH分解反应过程产生的大量氧自由基增加了内源性活性氧含量,从而参与氧化应激与炎症反应过程。因此,近年来对GGT的关注重点逐渐拓展到骨质破坏,包括骨质疏松、骨营养不良、骨性关节炎等方面。被认为是患病风险评估、病情活动度判断及预后评价的重要参考。本文综述了GGT的自身特性及其在骨破坏相关疾病发生发展中的意义,为临床诊实践提供借鉴。

Gamma-glutamyltranspeptidase (GGT) is an essential enzyme in glutathione metabolism, which is mainly produced by the liver, excreted through the biliary tract and widely distributed in many tissues and organs throughout the body. For many years, GGT has been used as diagnosis and treatment evaluation in extensive diseases. Studies have shown that GGT is a key factor in regulating the oxidation-reduction balance of cells and their surrounding environment. The large amount of oxygen free radicals generated in the GSH decomposition reaction catalyzed by GGT increased the content of endogenous reactive oxygen species, thus participated in the process of oxidative stress and inflammation. In recent years, research about GGT has gradually expanded to bone destruction related diseases, including osteoporosis, bone malnutrition, osteoarthritis and other aspects. Also included cardiovascular, respiratory, metabolic, tumor, immune and other diseases, which is considered as an important reference for risk assessment, disease activity judgment and prognosis evaluation. The role of GGT in the body is more complex than our current cognition, and the pathways involved in different diseases may not be limited to oxidative stress or metabolic abnormalities, which still need more in-depth research. GGT is easy detect clinically and can be used as a reference for evaluation and prognosis of specific diseases. GGT inhibitors significantly reduced the number of osteoclasts in vitro and the degree of bone erosion in arthritic mice. These results suggest that GGT inhibitors or antagonists may be a novel therapeutic agent for alleviating PsA joint symptoms. This paper reviews the characteristics of GGT and its significance in the occurrence and development of various diseases, providing reference for clinical practice.

图1 GGT最经典的反应是GSH循环,借此参与氧化应激与炎症反应,还可单独通过激活RaS系统激发氧化应激的过程
图2 GGT与骨质破坏相关疾病关系简图,GGT可通过直接作用于破骨细胞前体、上调骨吸收因子表达、激活氧化应激反应物等途径,参与骨质破坏相关的疾病。其中:RANKL :核因子kappaB受体激活物配体(receptor activator of nuclear factor kappa B ligand);MCP-1:单核细胞趋化蛋白-1(monocyte chemotactic protein 1);VEGF-A:血管内皮生长因子A(vascular endothelial growth factor A);TNF-C:肿瘤坏死因子C(tumor necrosis factor C,TNF-C);IL-1β:白细胞介素1β(interleukin-1 β);TLR4:Toll样受体4(Toll-like receptors 4);PTHrP:甲状旁腺激素相关蛋白(parathyroid hormone-related protein);IL-11:白细胞介素11(interleukin-11);ROS:内源性活性氧(reactive oxygen species);NO:一氧化氮(nitric oxide)
47
Cantin AM, North SL, Hubbard RC, et al. Normal alveolar epithelial lining fluid contains high levels of glutathione [J]. J Appl Physiol (1985), 1987, 63(1): 152-157.
48
Carr AC, Winterbourn CC. Oxidation of neutrophil glutathione and protein thiols by myeloperoxidase-derived hypochlorous acid [J]. Biochem J, 1997, 327 (Pt 1)(Pt 1): 275-281.
49
Lowry MH, Mcallister BP, Jean JC, et al. Lung lining fluid glutathione attenuates IL-13-induced asthma [J]. Am J Respir Cell Mol Biol, 2008, 38(5): 509-516.
50
Corti A, Franzini M, Cianchetti S, et al. Contribution by polymorphonucleate granulocytes to elevated gamma-glutamyltransferase in cystic fibrosis sputum [J]. PLoS One, 2012, 7(4): e34772.
51
Shao T, Tong Y, Lu S, et al. γ-Glutamyltransferase elevations are frequent in patients with COVID-19: A clinical epidemiologic study [J]. Hepatol Commun, 2020, 4(12): 1744-1750.
52
Maguin GK, Lartaud I, Giummelly P, et al. Accurate measurement of reduced glutathione in gamma-glutamyltransferase-rich brain microvessel fractions [J]. Brain Res, 2011, 1369: 95-102.
53
Hogg N, Singh RJ, Konorev E, et al. S-Nitrosoglutathione as a substrate for gamma-glutamyl transpeptidase [J]. Biochem J, 1997, 323(Pt 2)(Pt 2): 477-481.
54
Dahboul F, Leroy P, Maguin GK, et al. Endothelial gamma-glutamyltransferase contributes to the vasorelaxant effect of S-nitrosoglutathione in rat aorta [J]. PLoS One, 2012, 7(9): e43190.
55
Zheng MQ, Tang K, Zimmerman MC, et al. Role of gamma-glutamyl transpeptidase in redox regulation of K+ Channel remodeling in postmyocardial infarction rat hearts [J]. Am J Physiol Cell Physiol, 2009, 297(2): C253-C262.
56
Mendiola AS, Ryu JK, Bardehle S, et al. Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation [J]. Nat Immunol, 2020, 21(5): 513-524.
57
Kivimäki M, Luukkonen R, Batty GD, et al. Body mass index and risk of dementia: Analysis of individual-level data from 1.3 million individuals [J]. Alzheimers Dement, 2018, 14(5): 601-609.
58
Wei X, Fan X, Feng Z, et al. Ethyl acetate extract of herpetospermum pedunculosum alleviates α-naphthylisothiocyanate-induced cholestasis by activating the farnesoid x receptor and suppressing oxidative stress and inflammation in rats [J]. Phytomedicine, 2020, 76: 153257.
1
Grillo MP. Drug-S-acyl-glutathione thioesters: synthesis, bioanalytical properties, chemical reactivity, biological formation and degradation [J]. Curr Drug Metab, 2011, 12(3): 229-244.
2
Mayatepek E, Okun JG, Meissner T, et al. Synthesis and metabolism of leukotrienes in gamma-glutamyl transpeptidase deficiency [J]. J Lipid Res, 2004, 45(5): 900-904.
3
Bulusu S, Sharma M. What does serum γ-glutamyltransferase tell us as a cardiometabolic risk marker? [J]. Ann Clin Biochem, 2016, 53(Pt 3): 312-332.
4
Heisterkamp N, Groffen J, Warburton D, et al. The human gamma-glutamyltransferase gene family [J]. Hum Genet, 2008, 123(4): 321-332.
5
Vergneault H, Vandebeuque E, Codullo V, et al. Disease activity score in 28 joints using GGT permits a dual evaluation of joint activity and cardiovascular risk [J]. J Rheumatol, 2020, 47(12): 1738-1745.
6
Kunutsor SK. Gamma-glutamyltransferase-friend or foe within? [J]. Liver International, 2016, 36(12): 1723-1734.
7
Aoyama K. Glutathione in the Brain [J]. Int J Mol Sci, 2021, 22(9).
8
Oestreicher J,Morgan B.Glutathione: subcellular distribution and membrane transport (1)[J].Biochem Cell Biol,2019,97(3):270-289.
9
Corti A, Belcastro E, Dominici S, et al. The dark side of gamma-glutamyltransferase (GGT): Pathogenic effects of an 'antioxidant' enzyme [J]. Free Radic Biol Med, 2020, 160: 807-819.
10
Anderson ME, Meister A. Inhibition of gamma-glutamyl transpeptidase and induction of glutathionuria by gamma-glutamyl amino acids [J]. Proc Natl Acad Sci U S A, 1986, 83(14): 5029-5032.
11
Lieberman MW, Wiseman AL, Shi ZZ, et al. Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice [J]. Proc Natl Acad Sci U S A, 1996, 93(15): 7923-7926.
12
Harding CO, Williams P, Wagner E, et al. Mice with genetic gamma-glutamyl transpeptidase deficiency exhibit glutathionuria, severe growth failure, reduced Life spans, and infertility [J]. J Biol Chem, 1997, 272(19): 12560-12567.
13
Cho AR, Kwon YJ, Lim HJ, et al. Oxidative balance score and serum γ-glutamyltransferase level among Korean adults: a nationwide population-based study [J]. Eur J Nutr, 2018, 57(3): 1237-1244.
14
Uçar H, Gür M, Gözükara MY, et al. Gamma glutamyl transferase activity is independently associated with oxidative stress rather than SYNTAX score [J]. Scand J Clin Lab Invest, 2015, 75(1): 7-12.
15
Pandur S, Pankiv S, Johannessen M, et al. Gamma-glutamyltransferase is upregulated after oxidative stress through the Ras signal transduction pathway in rat colon carcinoma cells [J]. Free Radic Res, 2007, 41(12): 1376-1384.
16
Spear N, Aust SD. Thiol-mediated NTA-Fe(III) reduction and lipid peroxidation [J]. Arch Biochem Biophys, 1994, 312(1): 198-202.
17
Whitfield JB. Gamma glutamyl transferase [J]. Crit Rev Clin Lab Sci, 2001, 38(4): 263-355.
18
Jaganjac M,Cindri,M,Jakov evi A, et al.Lipid peroxidation in brain tumors[J].Neurochem Int,2021,149:105118.
19
Su LJ, Zhang JH, Gomez H, et al. Reactive Oxygen Species-Induced lipid peroxidation in apoptosis, autophagy, and ferroptosis [J]. Oxid Med Cell Longev, 2019: 5080843.
20
Minotti G. Sources and role of Iron in lipid peroxidation [J]. Chem Res Toxicol, 1993, 6(2): 134-146.
21
Abdulkhaleq L. A.1,2, Assi M. A.3,4, Abdullah Rasedee.The crucial roles of inflammatory mediators in inflammation: A review.Veterinary World [J].2018,11(5): 627-635.
22
Spoto B, D'arrigo G, Tripepi G, et al. Serum gamma-glutamyltransferase, oxidized LDL and mortality in the elderly [J]. Aging Clin Exp Res, 2021, 33(5): 1393-1397.
23
张书勤,张群,谢登辉.柠檬酸在骨质疏松疾病中作用的研究进展[J].中华老年骨科与康复电子杂志, 2021, 7(4): 245-251.
24
文学,孙红,王洪,等. PTHrP类似物阿巴洛肽在骨质疏松症中的研究进展[J].中华老年骨科与康复电子杂志, 2021, 7(2): 117-121.
25
Miller PD. Management of severe osteoporosis [J]. Expert Opin Pharmacother, 2016, 17(4): 473-488.
26
Niida S, Kawahara M, Ishizuka Y, et al. Gamma-glutamyltranspeptidase stimulates receptor activator of nuclear factor-kappaB ligand expression Independent of its enzymatic activity and serves as a pathological bone-resorbing factor [J]. J Biol Chem, 2004, 279(7): 5752-5756.
27
Lu Ke, Shi Tian-Shu, Shen Si-Yu, et al. Defects in a liver-bone axis contribute to hepatic osteodystrophy disease progression [J]. Cell Metab, 2022, 34(3): 441-577.
28
Kawazoe Y, Miyauchi M, Nagasaki A, et al. Osteodystrophy in cholestatic liver diseases is attenuated by Anti-γ-Glutamyl transpeptidase antibody [J]. PLoS One, 2015, 10(9): e0139620.
29
郑义,康凯,王智杰,等.中枢敏化及其对膝关节骨关节炎临床治疗的影响[J].中华老年骨科与康复电子杂志, 2020, 6(4): 243-247.
30
Ishizuka Y, Moriwaki S, Kawahara-Hanaoka M, et al. Treatment with anti-gamma-glutamyl transpeptidase antibody attenuates osteolysis in collagen-induced arthritis mice [J]. J Bone Miner Res, 2007, 22(12): 1933-1942.
31
杨利,李强,阚志芸,等.阿仑磷酸钠对糖尿病骨质疏松症患者骨代谢的影响[J].中华老年骨科与康复电子杂志, 2020, 6(6): 351-356.
32
Chen Y, Ma B, Wang X, et al. Potential functions of the BMP family in bone, obesity, and glucose metabolism [J]. J Diabetes Res, 2021: 6707464.
33
Lu GH, Gong SG, Li C, et al. Prognostic value of Gamma-Glutamyltransferase in male patients with idiopathic pulmonary arterial hypertension [J]. Front Cardiovasc Med, 2020, 7: 580908.
34
Fraser A, Harris R, Sattar N, et al. Alanine aminotransferase, gamma-glutamyltransferase, and incident diabetes: the British Women's Heart and Health Study and meta-analysis [J]. Diabetes Care, 2009, 32(4): 741-750.
35
Kunutsor SK, Abbasi A, Adler AI. Gamma-glutamyl transferase and risk of type II diabetes: an updated systematic review and dose-response meta-analysis [J]. Ann Epidemiol, 2014, 24(11): 809-816.
36
Khukhlina OS, Liakhovych OD, Kaniovska LV, et al. Features of some anthropometric indices and indices of insulin resistance in patients with non-alcoholic steatohepatitis on the background of obesity and osteoarthritis [J]. Wiad Lek, 2020, 73(4): 746-750.
37
Hanigan MH, Frierson HF Jr, Swanson PE, et al. Altered expression of gamma-glutamyl transpeptidase in human tumors [J]. Hum Pathol, 1999, 30(3): 300-305.
38
Lipsky MM, Hinton D, Klaunig JE, et al. Gamma glutamyl transpeptidase in safrole-induced, presumptive premalignant mouse hepatocytes [J]. Carcinogenesis, 1980, 1(2): 151-156.
39
Hanigan MH, Gallagher BC, Townsend DM, et al. Gamma-glutamyl transpeptidase accelerates tumor growth and increases the resistance of tumors to cisplatin in vivo [J]. Carcinogenesis, 1999, 20(4): 553-559.
40
Hanigan MH. Gamma-glutamyl transpeptidase: redox regulation and drug resistance [J]. Adv Cancer Res, 2014, 122: 103-141.
41
Del Bello B, Paolicchi A, Comporti M, et al. Hydrogen peroxide produced during gamma-glutamyl transpeptidase activity is involved in prevention of apoptosis and maintainance of proliferation in U937 cells [J]. FASEB J, 1999, 13(1): 69-79.
42
Corti A, Duarte TL, Giommarelli C, et al. Membrane gamma-glutamyl transferase activity promotes iron-dependent oxidative DNA damage in melanoma cells [J]. Mutat Res, 2009, 669(1/2): 112-121.
43
Kawakami K, Fujita Y, Matsuda Y, et al. Gamma-glutamyltransferase activity in exosomes as a potential marker for prostate cancer [J]. BMC Cancer, 2017, 17(1): 316.
44
Moriwaki S, Into T, Suzuki K, et al. γ-Glutamyltranspeptidase is an endogenous activator of toll-like receptor 4-mediated osteoclastogenesis [J]. Sci Rep, 2016, 6: 35930.
45
Wang A, Bai Y. Dendritic cells: The driver of psoriasis [J]. J Dermatol, 2020, 47(2): 104-113.
46
Elhosseiny NM, Elhezawy NB, Sayed RM, et al. γ-Glutamyltransferase as a novel virulence factor of acinetobacter baumannii inducing alveolar wall destruction and renal damage in systemic disease [J]. J Infect Dis, 2020, 222(5): 871-879.
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