The protective effect of Arginase inhibitor on retinal microvascular endothelial cells in high glucose cultures_Chinese Journal of Ocular Fundus Diseases

Authors：

Zhang Wei , Jiang Jianhong ,  Chen Song , He Guanghui , Yang Jing , Ma Yingxue , Chen Li , Song Jian

Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Clinical College of Ophthalmology Tianjin Medical University, Tianjin 300020, China;

Corresponding author：

Chen Song, Email: chensong20@hotmail.com

Keywords：

Arginase/antagonists & inhibitors; Retinal Vessels/cytology; Endothelial cells/physiology; Cells, cultured

DOI：

10.3760/cma.j.issn.1005-1015.2017.03.014

Video：

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Objective To investigate the effect of arginase (Arg) inhibitor N-ω-Hydroxy-L nor-Arginine (nor-NOHA) on high glucose cultured rhesus macaque retinal vascular endothelial cell line (RF/6A) in vitro. Methods The RF/6A cells were divided into the following 4 groups: normal control group (5.0 mmol/L of glucose, group A), high glucose group (25.0 mmol/L, group B), high glucose with 125 mg/L nor-NOHA group (group C), and high glucose with 1% DMSO group (group D). The proliferation, migration ability and angiogenic ability of RF/6A cells were measured by Methyl thiazolyl tetrazolium (MTT), transwell chamber and tube assay respectively. The express of Arg I, eNOS, iNOS mRNA of RF/6A cells were measured by real-time polymerase chain reaction (RT-PCR), Enzyme-linked immuno sorbent assay (ELISA) was used to detect the expression of NO and interleukine (IL)-1b of RF/6A cells. Results The proliferation, migration, and tube formation ability of group A (t=2.367, 5.633, 7.045;P＜0.05) and group C (t=5.260, 6.952, 8.875;P＜0.05) were significantly higher than group B. RT-PCR results showed the Arg I and iNOS expression in group B was higher than that in group A (t=6.836, 3.342;P＜0.05) and group C (t=4.904, 7.192;P＜0.05). The eNOS expression in group B was lower than that in group A and group C (t=4.165, 6.594;P＜0.05). ELISA results showed NO expression in group B was lower than that in group A and group C (t=4.925, 5.368;P＜0.05). IL-1b expression in group B was higher than that in group A and group C (t=5.032, 7.792;P＜0.05). Conclusions Nor-NOHA has a protective effect on cultured RF/6A cells in vitro and can enhance its proliferation, migration and tube formation. The mechanism may be inhibiting the oxidative stress by balancing the expression of Arg/NOS.

Citation： Zhang Wei, Jiang Jianhong, Chen Song, He Guanghui, Yang Jing, Ma Yingxue, Chen Li, Song Jian. The protective effect of Arginase inhibitor on retinal microvascular endothelial cells in high glucose cultures. Chinese Journal of Ocular Fundus Diseases, 2017, 33(3): 281-285. doi: 10.3760/cma.j.issn.1005-1015.2017.03.014 Copy

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1. 郑志. 糖尿病视网膜病变临床防治: 进展、挑战与展望[J]. 中华眼底病杂志, 2012, 28(3): 209-214. DOI: 10.3760/cma.j.issn.1005-1015.2012.03.001.Zheng Z. Prevention and treatment of diabetic retinopathy: progress, challenges and future prospects[J]. Chin J Ocul Fundus Dis, 2012, 28(3): 209-214. DOI: 10.3760/cma.j.issn.1005-1015.2012.03.001.
2. Morris SM Jr. ArgⅠnases and ArgⅠnine deficiency syndromes[J]. Curr Opin Clin Nutr Metab Care, 2012, 15(1): 64-70. DOI: 10.1097/MCO.0b013e32834d1a08.
3. Zhou L, Sun CB, Liu C, et al. Upregulation of ArgⅠnase activity contributes to intracellular ROS production induced by high glucose in H9c2 cells[J]. Int J Clin Exp Pathol, 2015, 8(3): 2728-2736.
4. Shemyakin A, Kövamees O, Rafnsson A, et al. Arginase inhibition improves endothelial function in patients with coronary artery disease and type 2 diabetes mellitus[J]. Circulation, 2012, 126(25): 2943-2950. DOI: 10.1161/CIRCULATIONAHA.112.140335.
5. Nakano M, Nagaishi K, Konari N, et al. Bone marrow-derived mesenchymal stem cells improve diabetes-induced cognitive impairment by exosome transfer into damaged neurons and astrocytes[J]. Sci Rep, 2016, 22(6): 24805. DOI: 10.1038/srep24805.
6. Yamagishi S, Matsui T. Advanced glycation end products (AGEs), oxidative stress and diabetic retinopathy[J]. Curr Pharm Biotechnol, 2011, 12(3): 362-368.
7. Henno P, Maurey C, Le Pimpec-Barthes F, et al. Is ArgⅠnase a potential drug target in tobacco-induced pulmonary endothelial dysfunction?[J]. Respir Res, 2015, 16: 46. DOI: 10.1186/s12931-015-0196-4.
8. Delage B, Fennell DA, Nicholson L, et al. ArgⅠnine deprivation and ArgⅠninosuccinate synthetase expression in the treatment of cancer[J]. Int J Cancer, 2010, 126(12): 2762-2772. DOI: 10.1002/ijc.25202.
9. Tekmen-Clark M, Gleason E. Nitric oxide production and the expression of two nitric oxide synthases in the avian retina[J]. Vis Neurosci, 2013, 30(3): 91-103. DOI: 10.1017/S0952523813000126.
10. Elms SC, Toque HA, Rojas M, et al. The role of ArgⅠnase Ⅰ in diabetes-induced retinal vascular dysfunction in mouse and rat models of diabetes[J]. Diabetologia, 2013, 56(3): 654-662. DOI: 10.1007/s00125-012-2789-5.
11. Romero MJ, Iddings JA, Platt DH, et al. Diabetes-induced vascular dysfunction involves ArgⅠnaseⅠ[J]. Am J Physiol Heart Circ Physiol, 2012, 302(1): 159-166. DOI: 10.1152/ajpheart.00774.2011.
12. Patel C, Rojas M, Narayanan SP, et al. ArgⅠnase as a mediator of diabetic retinopathy[J]. Front Immunol, 2013, 4: 173. DOI: 10.3389/fimmu.2013.00173.
13. Kuo L, Hein TW. Vasomotor regulation of coronary microcirculation by oxidative stress: role of ArgⅠnase[J]. Front Immunol, 2013, 4: 237. DOI: 10.3389/fimmu.2013.00237.
14. Kövamees O, Shemyakin A, Pernow J. Effect of ArgⅠnase inhibition on ischemia-reperfusion injury in patients with coronary artery disease with and without diabetes mellitus[J/OL]. PLoS One, 2014, 9(7): 103260[2014-07-29]. . DOI: 10.1371/journal.pone.0103260.
15. Xiong Y, Yepuri G, Forbiteh M, et al. ARG2 impairs endothelial autophagy through regulation of MTOR and PRKAA/AMPK signaling in advanced atherosclerosis[J]. Autophagy, 2014, 10(12): 2223-2238. DOI: 10.4161/15548627.2014.981789.
16. Moon J, Do HJ, Cho Y, et al. ArgⅠnase inhibition ameliorates hepatic metabolic abnormalities in obese mice[J/OL]. PLoS One, 2014, 9(7): 103048[2014-07-24]. . DOI: 10.1371/journal.pone.0103048.

Chinese Journal of Ocular Fundus Diseases

The protective effect of Arginase inhibitor on retinal microvascular endothelial cells in high glucose cultures

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