Effect of 5,6-dihydrocyclopenta-1, 2-dithiole-3-thione on Müller cells under the high glucose_Chinese Journal of Ocular Fundus Diseases

Authors：

Huang Qi , Tian Min , Zhou Qi ,  Lyu Hongbin

Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Lu Zhou 646000, China;

Corresponding author：

Lyu Hongbin, Email: coulistlvhongbin@163.com

Keywords：

Diabetic retinopathy/pathophysiology; Microglia; NF-E2-related factor 2; Heme oxygenase (decyclizing); bcl-2-Associated X Protein

DOI：

10.3760/cma.j.issn.1005-1015.2017.03.016

Video：

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Objective To investigate the cellular viability and mitochondrial reactive oxygen species (ROS) production of the Müller cells under high glucose condition, and explore the protection role of the 5,6-dihydrocyclopenta-1, 2-dithiole-3-thione (CPDT) on Müller cells. Methods Müller cells from Sprague Dawley rats were divided into 5 groups randomly, including 25 mmol/L normal glucose group (group A) and 65 mmol/L high glucose group (group B). High glucose group with 45, 60, 70 μmol/L CPDT and cultured them 72 hour was set as group C, D and E. Water soluble tetrazolium salt (WST)-8 was used to measure the cellular viability. Flow cytometry was used to measure the active oxygen and apoptosis index. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), Bcl-2 and Bax protein were measured by Western blot. Results Compared with group A, the WST-8 showed that the viability of Müller cells apparently decreased in group B (t=39.59,P＜0.05). Compared with the group B, the viability of Müller cells had changes in group C (t=0.97,P＞0.05), but recovered in group D and E (t=−4.17, −7.52;P＜0.05). Compared with group A, the FCM showed that the mitochondrial ROS levels was higher in group B (t=−30.99,P＜0.05). Compared with group B, the mitochondrial ROS levels were decreased in group D (t=27.68,P＜0.05). Compared with group A, Bax, Nrf2 and HO-1 increased (t=–11.03, –63.17, –11.44;P＜0.05), while the bcl-2 decreased in group B (t=7.861,P＜0.05). Compared with the group B, Nrf2, HO-1 and Bax decreased (t=15.11, 26.59, 6.27;P＜0.05), while the bcl-2 increased in group D (t=−6.53,P＜0.05). Conclusions Under the high glucose, CPDT may reduce the mitochondrial ROS levels and the expression of Nrf2, HO-1 and Bax protein of Müller cells. It may inhibit apoptosis through activating the Nrf2/HO-1 pathway and balancing of level of Bcl-2 protein and mitochondrial ROS.

Citation： Huang Qi, Tian Min, Zhou Qi, Lyu Hongbin. Effect of 5,6-dihydrocyclopenta-1, 2-dithiole-3-thione on Müller cells under the high glucose. Chinese Journal of Ocular Fundus Diseases, 2017, 33(3): 290-294. doi: 10.3760/cma.j.issn.1005-1015.2017.03.016 Copy

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12.	Hara H, Ohta M, Ohta K, et al. Increase of antioxidative potential by tert-butylhydroquinone protects against cell death associated with 6-hydroxydopamine-induced oxidative stress in neuroblastoma SH-SY5Y cells [J]. Brain Res Mol Brain Res, 2003, 119(2): 125-131.
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14.	Yang X, Yao W, Shi H, et al. Paeoniflorin protects Schwann cells against high glucose induced oxidative injury by activating Nrf2/ARE pathway and inhibiting apoptosis [J]. J Ethnopharmacol, 2016, 185: 361-369. DOI: 10.1016/j.jep.2016.03.031.
15.	李晶艳, 田敏, 张思远, 等.叔丁基对二酚对二型糖尿病大鼠视神经核因子E2相关因子、血红素氧合酶1表达的影响[J]. 中华眼底病杂志, 2015, 31(6): 581-585. DOI: 10.3760/cma.j.issn.1005-1015.2015.06.017.Li JY, Tian M, Zhang SY, et al. The influence of tert-butyl hydroquinone on retinal nuclear factor E2-related factor 2 and heme oxygenase-1 in type 2 diabetic rats [J]. Chin J Ocul Fundus Dis, 2015, 31(6): 581-585. DOI: 10.3760/cma.j.issn.1005-1015.2015.06.017.

1. Zhu T, Ma J, Li Y, et al. Association between retinal neuronal degeneration and visual function impairment in type 2 diabetic patients without diabetic retinopathy [J]. Sci China Life Sci, 2015, 58(6): 550-555. DOI: 10.1007/s11427-015-4858-8.
2. Atkin M, Laight D, Cummings MH. The effects of garlic extract upon endothelial function, vascular inflammation, oxidative stress and insulin resistance in adults with type 2 diabetes at high cardiovascular risk: a pilot double blind randomized placebo controlled trial [J]. J Diabetes Complications, 2016, 30(4): 723-727. DOI: 10.1016/j.jdiacomp.2016.01.003.
3. Long L, Wang J, Lu X, et al. Protective effects of scutellarin on type Ⅱdiabetes mellitus-induced testicular damages related to reactive oxygen species/Bcl-2/Bax and reactive oxygen species/micro-circulation/staving pathway in diabetic rat [J/OL]. J Diabetes Res, 2015, 2015: 252530[2015-0312]. . DOI: 10.1155/2015/252530.
4. Deliyanti D, Lee JY, Petratos S, et al. A potent Nrf2 activator, dh404, bolsters antioxidant capacity in glial cells and attenuates ischaemic retinopathy [J]. Clin Sci (Lond), 2016, 130 (15): 1375-1387. DOI: 10.1042/CS20160068.
5. Jin W, Wang H, Yan W, et al. Role of Nrf2 in protection against traumatic brain injury in mice [J]. J Neurotrauma, 2009, 26(1): 131-139. DOI: 10.1089/neu.2008.0655.
6. Miano JM, Berk BC.Retinoids: versatile biological response modifiers of vascular smooth muscle phenotype [J]. Circ Res, 2000, 87(5): 355-362.
7. Li Y, Paonessa JD, Zhang Y. Mechanism of chemical activation of Nrf2 [J/OL]. PLoS One, 2012, 7(4): 35122[2012-04-25]. . DOI: 10.1371/journal.pone.0035122.
8. Han N, Yu L, Song Z, et al. Agmatine protects Müller cells from high-concentration glucose-induced cell damage via N-methyl-D-aspartic acid receptor inhibition [J]. Mol Med Rep, 2015, 12(1): 1098-1106. DOI: 10.3892/mmr.2015.3540.
9. 李文君, 霍晶, 于文畅. Müller细胞与糖尿病性视网膜病变发生及早期诊断的研究进展[J]. 中国实验诊断学, 2014, 18(2): 332-333.Li WJ, Huo J, Yu WC, et al. The advances in the occurrence and early diagnosis of müller cells and diabetic retinopathy [J]. Chin J Lab Diagn, 2014, 18(2): 332-333.
10. Nabavi SF, Barber AJ, Spagnuolo C, et al. Nrf2 as molecular target for polyphenols: a novel therapeutic strategy in diabetic retinopathy [J]. Crit Rev Clin Lab Sci, 2016, 53(5): 293-312. DOI: 10.3109/10408363.2015.1129530.
11. Jais A, Einwallner E, Sharif O, et al. Heme oxygenase-1 drives metaflammation and insulin resistance in mouse and man [J]. Cell, 2014, 158(1): 25-40. DOI: 10.1016/j.cell.2014.04.043.
12. Hara H, Ohta M, Ohta K, et al. Increase of antioxidative potential by tert-butylhydroquinone protects against cell death associated with 6-hydroxydopamine-induced oxidative stress in neuroblastoma SH-SY5Y cells [J]. Brain Res Mol Brain Res, 2003, 119(2): 125-131.
13. Gozzelino R, Jeney V, Soares MP. Mechanisms of cell protection by heme oxygenase-1 [J]. Annu Rev Pharmacol Toxicol, 2010, 50: 323-354. DOI: 10.1146/annurev.pharmtox.010909.105600.
14. Yang X, Yao W, Shi H, et al. Paeoniflorin protects Schwann cells against high glucose induced oxidative injury by activating Nrf2/ARE pathway and inhibiting apoptosis [J]. J Ethnopharmacol, 2016, 185: 361-369. DOI: 10.1016/j.jep.2016.03.031.
15. 李晶艳, 田敏, 张思远, 等.叔丁基对二酚对二型糖尿病大鼠视神经核因子E2相关因子、血红素氧合酶1表达的影响[J]. 中华眼底病杂志, 2015, 31(6): 581-585. DOI: 10.3760/cma.j.issn.1005-1015.2015.06.017.Li JY, Tian M, Zhang SY, et al. The influence of tert-butyl hydroquinone on retinal nuclear factor E2-related factor 2 and heme oxygenase-1 in type 2 diabetic rats [J]. Chin J Ocul Fundus Dis, 2015, 31(6): 581-585. DOI: 10.3760/cma.j.issn.1005-1015.2015.06.017.

Chinese Journal of Ocular Fundus Diseases

Effect of 5,6-dihydrocyclopenta-1, 2-dithiole-3-thione on Müller cells under the high glucose

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