Screen of compounds affecting the hypoxia induced-gene expression of retinal endothelial cells_Chinese Journal of Ocular Fundus Diseases

Authors：

Neonate Department, Guangdong Maternal and Child Health Hospital, Guangzhou 511442, China;

Corresponding author：

Keywords：

Retinopathy of prematurity/prevention & control; Gene expression; Forecasting; Computational biology

DOI：

10.3760/cma.j.issn.1005-1015.2016.06.007

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Objective To screen compounds or drugs can affect the hypoxia induced-gene expression of retinal vascular endothelial cell based on gene expression microarrays and connectivity map (CMAP) technology. Methods Totally 326 up-regulated and down-regulated genes of hypoxic human embryonic retinal microvascular endothelial cells minduced by cobalt chloride in the previous study were converted into query signature format documents. Gene profile of the disease characteristics was then compared with that of control in CMAP website database, positive and negative compounds related to retinopathy of prematurity (ROP) were finally screened out. Results 44 and 18 compounds or drugs have positive and negative relationship with ROP respectively by searching CMAP database with differentially expressed genes. Ciclopirox, cobalt chloride, gossypol and withaferin A have positive relationship with ROP. Cyclic adenosine monophosphate, harmalol, naringin and probenecid have a negative effect on ROP. Conclusions Ciclopirox, cobalt chloride, gossypol and withaferin A have a positive effect on ROP. However, cyclic adenosine monophosphate, harmalol, naringin and probenecid have a negative effect.

Citation： NieChuan, ZhangLiang, WangJunping, WangYue, ZhangChunyi, LuoXianqiong. Screen of compounds affecting the hypoxia induced-gene expression of retinal endothelial cells. Chinese Journal of Ocular Fundus Diseases, 2016, 32(6): 591-595. doi: 10.3760/cma.j.issn.1005-1015.2016.06.007 Copy

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11.	Yanni SE, Barnett JM, Clark ML, et al.The role of PGE2 receptor EP4 in pathologic ocular angiogenesis[J].Invest Ophthalmol Vis Sci, 2009, 50(11):5479-5486. DOI:10.1167/iovs.09-3652.
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13.	Ushio-Fukai M, Alexander RW.Reactive oxygen species as mediators of angiogenesis signaling:role of NAD (P) H oxidase[J].Mol Cell Biochem, 2004, 264(1-2):85-97.
14.	Quimson SK.Retinopathy of prematurity:pathogenesis and current treatment options[J].Neonatal Netw, 2015, 34(5):284-287. DOI:10.1891/0730-0832.34.5.284.
15.	石文静, 陈超, 胡宝洋, 等.新生小鼠视网膜病变的基因表达谱变化[J].中华围产医学杂志, 2006, 9(6):385-388.Shi WJ, Chen C, Hu BY, et al.Change of gene expression profile and its significance in mouse with oxygen induced retinopathy[J].Chin J Perinat Med, 2006, 9(6):385-388.
16.	Tea M, Fogarty R, Brereton HM, et al.Gene expression microarray analysis of early oxygen-induced retinopathy in the rat[J].J Ocul Biol Dis Infor, 2009, 2(4):190-201.
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19.	Hahm ER, Moura MB, Kelley EE, et al.Withaferin A-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species[J/OL].PLoS One, 2011, 6(8):23354[2011-08-10].http://dx.doi.org/10.1371/journal.pone.0023354.DOI:10.1371/journal.pone.0023354.
20.	Matsumiya W, Kusuhara S, Hayashibe K, et al.Forskolin modifies retinal vascular development in Mrp4-knockout mice[J].Invest Ophthalmol Vis Sci, 2012, 53(13):8029-8035. DOI:10.1167/iovs.12-10781.
21.	Moura DJ, Richter MF, Boeira JM, et al.Antioxidant properties of beta-carboline alkaloids are related to their antimutagenic and antigenotoxic activities[J]. Mutagenesis, 2007, 22(4):293-302.
22.	Schindler R, Mentlein R.Flavonoids and vitamin E reduce the release of the angiogenic peptide vascular endothelial growth factor from human tumor cells[J].J Nutr, 2006, 136(6):1477-1482.
23.	Keith TA, Radhakrishnan V, Moredock S, et al. Uptake of 3H-cAMP by retinal pigment epithelium isolated from bluegill sunfish (Lepomis macrochirus)[J].BMC Neurosci, 2006, 7:82.

1. Uddin MI, Evans SM, Craft JR, et al.In vivo imaging of retinal hypoxia in a model of oxygen-induced retinopathy[J/OL].Sci Rep, 2016, 6:31011[2016-08-05]. http://www.nature.com/articles/srep31011.DOI:10.1038/srep31011.
2. Beharry KD, Valencia GB, Lazzaro DR, et al.Pharmacologic interventions for the prevention and treatment of retinopathy of prematurity[J].Semin Perinatol, 2016, 40(3):189-202. DOI:10.1053/j.semperi.2015.12.006.
3. Lamb J, Crawford ED, Peck D, et al.The Connectivity Map:using gene-expression signatures to connect small molecules, genes, and disease[J]. Science, 2006, 313(5795):1929-1935.
4. Belizário JE, Sangiuliano BA, Perez-Sosa M, et al.Using pharmacogenomic databases for discovering patient-target genes and small molecule candidates to cancer therapy[J/OL].Front Pharmacol, 2016, 7:312[2016-09-29]. http://dx.doi.org/10.3389/fphar.2016.00312.
5. Yu L, Ma X, Zhang L, et al.Prediction of new drug indications based on clinical data and network modularity[J/OL].Sci Rep, 2016, 6:32530[2016-09-28].http://www.nature.com/articles/srep32530.DOI:10.1038/srep32530" target="_blank">10.1038/srep32530">http://www.nature.com/articles/srep32530.DOI:10.1038/srep32530.
6. Kim RS, Goossens N, Hoshida Y, et al.Use of big data in drug development for precision medicine[J].Expert Rev Precis Med Drug Dev, 2016, 1(3):245-253.
7. Quan Y, Li B, Sun YM, et al.Elucidating pharmacological mechanisms of natural medicines by biclustering analysis of the gene expression profile:a case study on curcumin and Si-Wu-Tang[J].Int J Mol Sci, 2014, 16(1):510-220. DOI:10.3390/ijms16010510.
8. Luo XQ, Zhang CY, Zhang JW, et al.Identification of iron homeostasis genes dysregulation potentially involved in retinopathy of prematurity pathogenicity by microarray analysis[J/OL].J Ophthalmol, 2015, 2015:584854[2015-10-18]. http://dx.doi.org/10.1155/2015/584854.DOI:10.1155/2015/584854" target="_blank">10.1155/2015/584854">http://dx.doi.org/10.1155/2015/584854.DOI:10.1155/2015/584854.
9. El-Remessy AB, Al-Shabrawey M, Platt DH, et al.Peroxynitrite mediates VEGF's angiogenic signal and function via a nitration-independent mechanism in endothelial cells[J].FASEB J, 2007, 21(10):2528-2539.
10. Hardy P, Beauchamp M, Sennlaub F, et al.New insights into the retinal circulation:inflammatory lipid mediators in ischemic retinopathy[J].Prostaglandins Leukot Essent Fatty Acids, 2005, 72(5):301-325.
11. Yanni SE, Barnett JM, Clark ML, et al.The role of PGE2 receptor EP4 in pathologic ocular angiogenesis[J].Invest Ophthalmol Vis Sci, 2009, 50(11):5479-5486. DOI:10.1167/iovs.09-3652.
12. Hellstr m A, Hård AL, Engstr m E, et al.Early weight gain predicts retinopathy in preterm infants:new, simple, efficient approach to screening[J].Pediatrics, 2009, 123(4):638-645.DOI:10.1542/peds.2008-2697.
13. Ushio-Fukai M, Alexander RW.Reactive oxygen species as mediators of angiogenesis signaling:role of NAD (P) H oxidase[J].Mol Cell Biochem, 2004, 264(1-2):85-97.
14. Quimson SK.Retinopathy of prematurity:pathogenesis and current treatment options[J].Neonatal Netw, 2015, 34(5):284-287. DOI:10.1891/0730-0832.34.5.284.
15. 石文静, 陈超, 胡宝洋, 等.新生小鼠视网膜病变的基因表达谱变化[J].中华围产医学杂志, 2006, 9(6):385-388.Shi WJ, Chen C, Hu BY, et al.Change of gene expression profile and its significance in mouse with oxygen induced retinopathy[J].Chin J Perinat Med, 2006, 9(6):385-388.
16. Tea M, Fogarty R, Brereton HM, et al.Gene expression microarray analysis of early oxygen-induced retinopathy in the rat[J].J Ocul Biol Dis Infor, 2009, 2(4):190-201.
17. Linden T, Katschinski DM, Eckhardt K, et al.The antimycotic ciclopirox olamine induces HIF-1alpha stability, VEGF expression, and angiogenesis[J].FASEB J, 2003, 17(6):761-763.
18. Arinbasarova AY, Medentsev AG, Krupyanko VI.Gossypol inhibits electron transport and stimulates ROS generation in yarrowia lipolytica mitochondria[J].Open Biochem J, 2012, 6:11-15. DOI:10.2174/1874091X01206010011.
19. Hahm ER, Moura MB, Kelley EE, et al.Withaferin A-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species[J/OL].PLoS One, 2011, 6(8):23354[2011-08-10].http://dx.doi.org/10.1371/journal.pone.0023354.DOI:10.1371/journal.pone.0023354" target="_blank">10.1371/journal.pone.0023354">http://dx.doi.org/10.1371/journal.pone.0023354.DOI:10.1371/journal.pone.0023354.
20. Matsumiya W, Kusuhara S, Hayashibe K, et al.Forskolin modifies retinal vascular development in Mrp4-knockout mice[J].Invest Ophthalmol Vis Sci, 2012, 53(13):8029-8035. DOI:10.1167/iovs.12-10781.
21. Moura DJ, Richter MF, Boeira JM, et al.Antioxidant properties of beta-carboline alkaloids are related to their antimutagenic and antigenotoxic activities[J]. Mutagenesis, 2007, 22(4):293-302.
22. Schindler R, Mentlein R.Flavonoids and vitamin E reduce the release of the angiogenic peptide vascular endothelial growth factor from human tumor cells[J].J Nutr, 2006, 136(6):1477-1482.
23. Keith TA, Radhakrishnan V, Moredock S, et al. Uptake of 3H-cAMP by retinal pigment epithelium isolated from bluegill sunfish (Lepomis macrochirus)[J].BMC Neurosci, 2006, 7:82.

Chinese Journal of Ocular Fundus Diseases

Screen of compounds affecting the hypoxia induced-gene expression of retinal endothelial cells

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