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Current Drug Metabolism

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ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

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Review Article

Research Progress of Epigenetic Modification on the Regulation of Transporters Under Hypoxia

Author(s): Yilan Zhao, Hongfang Mu, Anpeng Zhao, Shilan Feng and Rong Wang*

Volume 24, Issue 2, 2023

Published on: 17 April, 2023

Page: [106 - 113] Pages: 8

DOI: 10.2174/1389200224666230405115442

Price: $65

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Abstract

Epigenetic modification refers to the heritable changes caused by chromosomal changes without changing the DNA sequence. Epigenetics runs through the entire growth and differentiation process of the body, which causes varied diseases. Hypoxia is a physiological astate of lowered partial oxygen partial pressure that affects cell and tissue function. Transporters are proteins that maintain a normal and stable state of cells. Transporter's expression levels when hypoxia occurs influence the absorption, distribution, metabolism, and excretion of drugs, thereby affecting the utilization and efficacy of drugs. Epigenetic modification is assumed to play an important role in the metabolism of drugs. Changes in epigenetic modification and transporter expression levels under hypoxia are explored in our work, and the effect of epigenetic modification on transporter expression and how this regulatory mechanism works and affects drugs under hypoxia are questioned. It is important for drug development, treatment of diseases and rational use of drugs.

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[1]
Keogh, J.P. Membrane transporters in drug development. Adv. Pharmacol., 2012, 63(3), 1-42.
[PMID: 22776638]
[2]
Duan, Y.; Zhu, J.; Yang, J.; Gu, W.; Bai, X.; Liu, G.; Xiangyang, L. A decade’s review of miRNA: A center of transcriptional regulation of drugmetabolizing enzymes and transporters under hypoxia. Curr. Drug Metab., 2021, 22(9), 709-725.
[http://dx.doi.org/10.2174/1389200222666210514011313] [PMID: 33992050]
[3]
Lauschke, V.M.; Barragan, I.; Ingelman-Sundberg, M. Pharmacoepigenetics and toxicoepigenetics: Novel mechanistic insights and therapeutic opportunities. Annu. Rev. Pharmacol. Toxicol., 2018, 58(1), 161-185.
[http://dx.doi.org/10.1146/annurev-pharmtox-010617-053021] [PMID: 29029592]
[4]
Wojtal, K.A.; Cee, A.; Lang, S.; Götze, O.; Frühauf, H.; Geier, A.; Pastor-Anglada, M.; Torres-Torronteras, J.; Martí, R.; Fried, M.; Lutz, T.A.; Maggiorini, M.; Gassmann, M.; Rogler, G.; Vavricka, S.R. Downregulation of duodenal SLC transporters and activation of proinflammatory signaling constitute the early response to high altitude in humans. Am. J. Physiol. Gastrointest. Liver Physiol., 2014, 307(7), G673-G688.
[http://dx.doi.org/10.1152/ajpgi.00353.2013] [PMID: 24970780]
[5]
Zhang, M.; Yang, L.; Jia, Y.; Wang, T. Review of DNA and histone methylations on epigenetic regulation. Shengwu Jishu Tongbao, 2022, 38(7), 1-8.
[6]
Shi, Y.; Mi, S.; Yu, Y. Research progress on m6A epigenetic modification and its regulation mechanism. J Anim Sci, 2022, 49(01), 197-207.
[7]
Wen, Y.; Huang, K.; Shi, H.; Wu, Y.; Chen, Y. Research progress of m6A methylation modification. Chem. Life, 2022, 42(02), 275-282.
[8]
Rybnikova, E.; Samoilov, M. Epigenetic mechanisms of hypoxic preconditioning. Springerplus, 2015, 4(S1), L39.
[http://dx.doi.org/10.1186/2193-1801-4-S1-L39] [PMID: 27386200]
[9]
Zhou, G.Z. Screening of Differential Genes and Methylated Sites Based on Time Series after Human Expose to the High Altitude Master Thesis, Hunan Normal University, 2020.
[10]
Kovacsics, D.; Brózik, A.; Tihanyi, B.; Matula, Z.; Borsy, A.; Mészáros, N.; Szabó, E.; Németh, E.; Fóthi, Á.; Zámbó, B.; Szüts, D.; Várady, G.; Orbán, T.I.; Apáti, Á.; Sarkadi, B. Precision-engineered reporter cell lines reveal ABCG2 regulation in live lung cancer cells. Biochem. Pharmacol., 2020, 175, 113865.
[http://dx.doi.org/10.1016/j.bcp.2020.113865] [PMID: 32142727]
[11]
Xu, S.; Xu, X.; Zhang, Z.; Yan, L.; Zhang, L.; Du, L. The role of RNA m6A methylation in the regulation of postnatal hypoxia-induced pulmonary hypertension. Respir. Res., 2021, 22(1), 121.
[http://dx.doi.org/10.1186/s12931-021-01728-6] [PMID: 33902609]
[12]
Li, W.; Li, X.; Ma, X.; Xiao, W.; Zhang, J. Mapping the m1A, m5C, m6A and m7G methylation atlas in zebrafish brain under hypoxic conditions by MeRIP-seq. BMC Genomics, 2022, 23(1), 105.
[http://dx.doi.org/10.1186/s12864-022-08350-w] [PMID: 35135476]
[13]
Antonopoulos, A.S.; Margaritis, M.; Coutinho, P.; Shirodaria, C.; Psarros, C.; Herdman, L.; Sanna, F.; De Silva, R.; Petrou, M.; Sayeed, R.; Krasopoulos, G.; Lee, R.; Digby, J.; Reilly, S.; Bakogiannis, C.; Tousoulis, D.; Kessler, B.; Casadei, B.; Channon, K.M.; Antoniades, C. Adiponectin as a link between type 2 diabetes and vascular NADPH oxidase activity in the human arterial wall: The regulatory role of perivascular adipose tissue. Diabetes, 2015, 64(6), 2207-2219.
[http://dx.doi.org/10.2337/db14-1011] [PMID: 25552596]
[14]
Koprinarova, M.; Schnekenburger, M.; Diederich, M. Role of histone acetylation in cell cycle regulation. Curr. Top. Med. Chem., 2015, 16(7), 732-744.
[http://dx.doi.org/10.2174/1568026615666150825140822] [PMID: 26303420]
[15]
Bannister, A.J.; Miska, E.A. Regulation of gene expression by transcription factor acetylation. Cell. Mol. Life Sci., 2000, 57(8), 1184-1192.
[http://dx.doi.org/10.1007/PL00000758] [PMID: 11028911]
[16]
Zhao, S.; Fang, J. Advances in research on histone phosphorylation. J. Cell Biol., 2009, 31(02), 178-182.
[17]
Bahl, S.; Seto, E. Regulation of histone deacetylase activities and functions by phosphorylation and its physiological relevance. Cell. Mol. Life Sci., 2021, 78(2), 427-445.
[http://dx.doi.org/10.1007/s00018-020-03599-4] [PMID: 32683534]
[18]
Pérez-Cadahía, B.; Drobic, B.; Khan, P.; Shivashankar, C.C.; Davie, J.R. Current understanding and importance of histone phosphorylation in regulating chromatin biology. Curr. Opin. Drug Discov. Devel., 2010, 13(5), 613-622.
[PMID: 20812153]
[19]
Lu, L.; Li, D.; He, F.C. Bioinformatics advances in protein ubiquitination. Yi Chuan, 2013, 35(1), 17-26.
[http://dx.doi.org/10.3724/SP.J.1005.2013.00017] [PMID: 23357261]
[20]
Li, L.; Jiang, Y.; Wang, J.Z.; Liu, R.; Wang, X. Tau ubiquitination in Alzheimer’s disease. Front. Neurol., 2022, 12, 786353.
[http://dx.doi.org/10.3389/fneur.2021.786353] [PMID: 35211074]
[21]
Bian, Q.; Chai, S.; Ouyang, Z.; Liu, Y. Effect of tumor hypoxia on DNA and histone methylation. Anat. Sci. Educ., 2016, 22(05), 550-553.
[22]
Hala, D.; Huggett, D.B.; Burggren, W.W. Environmental stressors and the epigenome. Drug Discov. Today. Technol., 2014, 12, e3-e8.
[http://dx.doi.org/10.1016/j.ddtec.2012.05.004] [PMID: 25027372]
[23]
Moon, Y.; Kim, I.; Chang, S.; Park, B.; Lee, S.; Yoo, S.; Chae, S.; Hwang, D.; Park, H. Hypoxia regulates allele-specific histone modification of the imprinted H19 gene. Biochim. Biophys. Acta. Gene] Regul. Mech., 2020, 1863(11), 194643.
[http://dx.doi.org/10.1016/j.bbagrm.2020.194643] [PMID: 33035707]
[24]
Yang, Q.; Li, L. Effect of hypoxia on DNA methylation and histone acetylation related enzymes in astrocytes. Chinese J. Comparative Med., 2014, 24(01), 26-30.
[25]
Eddy, A.C.; Chapman, H.; George, E.M. Acute hypoxia and chronic ischemia induce differential total changes in placental epigenetic modifications. Reprod. Sci., 2019, 26(6), 766-773.
[http://dx.doi.org/10.1177/1933719118799193] [PMID: 30223723]
[26]
Chabert, C.; Khochbin, S.; Rousseaux, S.; Furze, R.; Smithers, N.; Prinjha, R.; Schlattner, U.; Pison, C.; Dubouchaud, H. Muscle hypertrophy in hypoxia with inflammation is controlled by bromodomain and extra-terminal domain proteins. Sci. Rep., 2017, 7(1), 12133.
[http://dx.doi.org/10.1038/s41598-017-12112-0] [PMID: 28935884]
[27]
Vetrovoy, O.V.; Glushchenko, T.S.; Sarieva, K.V.; Tyulkova, E.I.; Aramisova, R.M.; Samoilov, M.O. The acetylation of histone H3 at lys24 is accompanied by delayed expression of neuroprotective proteins Bcl-2 and BDNF in the neocortex of rats exposed to severe hypoxia: The effect of postconditioning. Neurochem. J., 2018, 12(3), 241-247.
[http://dx.doi.org/10.1134/S1819712418030157] [PMID: 29178418]
[28]
Huang, Y.; Tian, Y.; Zhao, Y.; Xue, C.; Zhan, J.; Liu, L.; He, X.; Zhang, L. Efficacy of the hypoxia-activated prodrug evofosfamide (TH-302) in nasopharyngeal carcinoma in vitro and in vivo. Cancer Commun., 2018, 38(1), 15.
[http://dx.doi.org/10.1186/s40880-018-0285-0] [PMID: 29764490]
[29]
Wrann, S.; Kaufmann, M.R.; Wirthner, R.; Stiehl, D.P.; Wenger, R.H. HIF mediated and DNA damage independent histone H2AX phosphorylation in chronic hypoxia. Biol. Chem., 2013, 394(4), 519-528.
[http://dx.doi.org/10.1515/hsz-2012-0311] [PMID: 23241668]
[30]
Chen, L.; Manautou, J.E.; Rasmussen, T.P.; Zhong, X. Development of precision medicine approaches based on inter-individual variability of BCRP/ABCG2. Acta Pharm. Sin. B, 2019, 9(4), 659-674.
[http://dx.doi.org/10.1016/j.apsb.2019.01.007] [PMID: 31384528]
[31]
Kim, I.; Choi, S.; Yoo, S.; Lee, M.; Park, J.W. AURKB, in concert with REST, acts as an oxygen-sensitive epigenetic regulator of the hypoxic induction of MDM2. BMB Rep., 2022, 55(6), 287-292.
[http://dx.doi.org/10.5483/BMBRep.2022.55.6.017] [PMID: 35410638]
[32]
Song, Y.K.; Hu, B.C.; Xu, L.; Liu, J.Q.; Chen, X.; Zheng, Y.; Chen, M.H.; Wang, J.Z.; Sun, R.H.; Mo, S.J. Productive transcription of miR-124-3p by RelA and RNA polymerase II directs RIP1 ubiquitination-dependent apoptosis resistance during hypoxia. Exp. Cell Res., 2019, 378(1), 21-31.
[http://dx.doi.org/10.1016/j.yexcr.2019.03.004] [PMID: 30844390]
[33]
Zhou, B.; Zhu, Y.; Xu, W.; Zhou, Q.; Tan, L.; Zhu, L.; Chen, H.; Feng, L.; Hou, T.; Wang, X.; Chen, D.; Jin, H. Hypoxia stimulates SUMOylation-dependent stabilization of KDM5B. Front. Cell Dev. Biol., 2021, 9, 741736.
[http://dx.doi.org/10.3389/fcell.2021.741736] [PMID: 34977006]
[34]
Sulkshane, P.; Ram, J.; Thakur, A.; Reis, N.; Kleifeld, O.; Glickman, M.H. Ubiquitination and receptor-mediated mitophagy converge to eliminate oxidation-damaged mitochondria during hypoxia. Redox Biol., 2021, 45, 102047.
[http://dx.doi.org/10.1016/j.redox.2021.102047] [PMID: 34175667]
[35]
Wang, Y.; Xu, B.; Liu, H.; Ji, C.; Yan, H. Research progress on the function and structure of solute carrier superfamily transporters. Xiandai Shengwu Yixue Jinzhan, 2017, 17(24), 4775-4793.
[36]
Rytting, E.; Audus, K.L. Effects of low oxygen levels on the expression and function of transporter OCTN2 in BeWo cells. J. Pharm. Pharmacol., 2010, 59(8), 1095-1102.
[http://dx.doi.org/10.1211/jpp.59.8.0006] [PMID: 17725851]
[37]
Mu, Y.; Li, W.; Wei, Z.; He, L.; Zhang, W.; Chen, X. Transcriptome analysis reveals molecular strategies in gills and heart of large yellow croaker (Larimichthys crocea) under hypoxia stress. Fish Shellfish Immunol., 2020, 104, 304-313.
[http://dx.doi.org/10.1016/j.fsi.2020.06.028] [PMID: 32544557]
[38]
Morgun, A.V.; Kuvacheva, N.V.; Khilazheva, E.D.; Pozhilenkova, E.A.; Gorina, Y.V.; Malinovskaya, N.A.; Komleva, Y.K.; Lopatina, O.L.; Panina, Y.A.; Gasymly, E.D.; Salmina, A.B. Perinatal brain injury is accompanied by disturbances in expression of SLC protein superfamily in endotheliocytes of hippocampal microvessels. Bull. Exp. Biol. Med., 2016, 161(6), 770-774.
[http://dx.doi.org/10.1007/s10517-016-3506-z] [PMID: 27783302]
[39]
Liu, X.; Liu, X. ABC family transporters and diabetes. Chinese J. Clini. Pharmacol. Therap., 2009, 14(12), 1428-1435.
[40]
Wang, Y.; Liu, Y.; Guo, Z.; Huang, H. Effect of hypoxia on the expression of ABCA1 and cholesterol efflux in raw264.7cells. Chinese J. Arteriosclerosis, 2011, 19(04), 315-318.
[41]
Lazarowski, A.; Caltana, L.; Merelli, A.; Rubio, M.D.; Ramos, A.J.; Brusco, A. Neuronal mdr-1 gene expression after experimental focal hypoxia: A new obstacle for neuroprotection? J. Neurol. Sci., 2007, 258(1-2), 84-92.
[http://dx.doi.org/10.1016/j.jns.2007.03.004] [PMID: 17459414]
[42]
Aviles-Reyes, R.X.; Angelo, M.F.; Villarreal, A.; Rios, H.; Lazarowski, A.; Ramos, A.J. Intermittent hypoxia during sleep induces reactive gliosis and limited neuronal death in rats: Implications for sleep apnea. J. Neurochem., 2010, 112(4), 854-869.
[http://dx.doi.org/10.1111/j.1471-4159.2009.06535.x] [PMID: 20002528]
[43]
Zolotoff, C.; Voirin, A.C.; Puech, C.; Roche, F.; Perek, N. Intermittent hypoxia and its impact on Nrf2/HIF-1α expression and abc transporters: An in vitro human blood-brain barrier model study. Cell. Physiol. Biochem., 2020, 54(6), 1231-1248.
[http://dx.doi.org/10.33594/000000311] [PMID: 33326735]
[44]
Qing, X.; Kong, B. Expression of ABCG2 and HIF-lα in hepatoma smmc-7721 cells under the anoxic conditions and their relationship. Chongqing Medicine, 2012, 41(07), 640-642.
[45]
Wang, Y.H. Epigenetic Regulation of Intestinal Peptide Transporter PEPT1 as a Potential Strategy for Colorectal Cancer Sensitization.PhD Thesis, Zhejiang University 2021.
[http://dx.doi.org/10.1038/s41419-021-03814-5]
[46]
Zhu, Q.Y. Study on Epigenetic Mechanism of OAT2 Transcriptional Inhibition in Hepatocellular Carcinoma., PhD Thesis, Zhejiang University, 2018.
[47]
Wang, Y.; Zhang, Y.; Huang, Y.; Chen, C.; Zhang, X.; Xing, Y.; Gu, Y.; Zhang, M.; Cai, L.; Xu, S.; Sun, B. Intratumor heterogeneity of breast cancer detected by epialleles shows association with hypoxic microenvironment. Theranostics, 2021, 11(9), 4403-4420.
[http://dx.doi.org/10.7150/thno.53737] [PMID: 33754068]
[48]
Chen, L.; Wang, Z.; Xu, Q.; Liu, Y.; Chen, L.; Guo, S.; Wang, H.; Zeng, K.; Liu, J.; Zeng, S.; Yu, L. The failure of DAC to induce OCT2 expression and its remission by hemoglobin-based nanocarriers under hypoxia in renal cell carcinoma. Theranostics, 2020, 10(8), 3562-3578.
[http://dx.doi.org/10.7150/thno.39944] [PMID: 32206108]
[49]
Liu, Y.; Zheng, X.; Yu, Q.; Wang, H.; Tan, F.; Zhu, Q.; Yuan, L.; Jiang, H.; Yu, L.; Zeng, S. Epigenetic activation of the drug transporter OCT2 sensitizes renal cell carcinoma to oxaliplatin. Sci. Transl. Med., 2016, 8(348), 348ra97.
[http://dx.doi.org/10.1126/scitranslmed.aaf3124] [PMID: 27440728]
[50]
Sharma, S.V.; Lee, D.Y.; Li, B.; Quinlan, M.P.; Takahashi, F.; Maheswaran, S.; McDermott, U.; Azizian, N.; Zou, L.; Fischbach, M.A.; Wong, K.K.; Brandstetter, K.; Wittner, B.; Ramaswamy, S.; Classon, M.; Settleman, J. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell, 2010, 141(1), 69-80.
[http://dx.doi.org/10.1016/j.cell.2010.02.027] [PMID: 20371346]
[51]
Yang, S.; Yang, Q.; Li, Y. Study on the etiology and pathogenesis of preeclampsia. J. Med. Inform., 2021, 34(04), 52-56.
[52]
Janzen, C.; Lei, M.Y.Y.; Cho, J.; Sullivan, P.; Shin, B.C.; Devaskar, S.U. Placental glucose transporter 3 (GLUT3) is up-regulated in human pregnancies complicated by late-onset intrauterine growth] restriction. Placenta, 2013, 34(11), 1072-1078.
[http://dx.doi.org/10.1016/j.placenta.2013.08.010] [PMID: 24011442]
[53]
Gorczyca, L.; Du, J.; Bircsak, K.M.; Wen, X.; Vetrano, A.M.; Aleksunes, L.M. Low oxygen tension differentially regulates the expression of placental solute carriers and ABC transporters. FEBS Lett., 2021, 595(6), 811-827.
[http://dx.doi.org/10.1002/1873-3468.13937] [PMID: 32978975]
[54]
Bouquet, F.; Ousset, M.; Biard, D.; Fallone, F.; Dauvillier, S.; Frit, P.; Salles, B.; Muller, C. A DNA-dependent stress response involving DNA-PK occurs in hypoxic cells and contributes to cellular adaptation to hypoxia. J. Cell Sci., 2011, 124(11), 1943-1951.
[http://dx.doi.org/10.1242/jcs.078030] [PMID: 21576354]
[55]
Nehra, S.; Bhardwaj, V.; Ganju, L.; Saraswat, D. Nanocurcumin prevents hypoxia induced stress in primary human ventricular cardiomyocytes by maintaining mitochondrial homeostasis. PLoS One, 2015, 10(9), e0139121.
[http://dx.doi.org/10.1371/journal.pone.0139121] [PMID: 26406246]
[56]
Hannan, A.J. Epimimetics: Novel therapeutics targeting epigenetic mediators and modulators. Trends Pharmacol. Sci., 2020, 41(4), 232-235.
[http://dx.doi.org/10.1016/j.tips.2020.01.005] [PMID: 32008853]
[57]
Li, C.; Li, X.; Xiao, J.; Liu, J.; Fan, X.; Fan, F.; Lei, H. Genetic changes in the EPAS1 gene between Tibetan and Han ethnic groups and adaptation to the plateau hypoxic environment. PeerJ, 2019, 7, e7943.
[http://dx.doi.org/10.7717/peerj.7943] [PMID: 31681516]
[58]
Liang, M.; Hao, M.; Li, Y.; Liu, X.; Zhang, S.; Wang, J. Screening of differential genes and methylated sites based on time series after human expose to the high altitude. Jiyinzuxue Yu Yingyong Shengwuxue, 2021, 40(Z4), 3765-3775.
[59]
Scherrer, U.; Allemann, Y.; Rexhaj, E.; Rimoldi, S.F.; Sartori, C. Mechanisms and drug therapy of pulmonary hypertension at high altitude. High Alt. Med. Biol., 2013, 14(2), 126-133.
[http://dx.doi.org/10.1089/ham.2013.1006] [PMID: 23795732]
[60]
Liu, J. The Research on DNA Methylation Profiles and the Effect of Related Genes MICU1 in High Altitude Adaptation., PhD Thesis Qinghai University, 2019.
[61]
Zhou, X.; Nian, Y.; Yang, M.; Xin, Y.; Qiao, Y.; Zhu, L.; Yang, J.; Li, X. The protein and mRNA expression of drug transports MDR1, MRP1 and BCRP after Exposure to high-altitude hypoxia. High Alt. Med. Biol., 2017, 38(03), 183-187.
[62]
Francois, L.N.; Gorczyca, L.; Du, J.; Bircsak, K.M.; Yen, E.; Wen, X.; Tu, M.J.; Yu, A.M.; Illsley, N.P.; Zamudio, S.; Aleksunes, L.M. Down-regulation of the placental BCRP/ABCG2 transporter in] response to hypoxia signaling. Placenta, 2017, 51, 57-63.
[http://dx.doi.org/10.1016/j.placenta.2017.01.125] [PMID: 28292469]
[63]
Luo, B.; Zhang, J.; Yang, T.; Zhang, J.; Li, W.; Wang, C.; Zhang, M.; Wang, R. Effect of amoxicillin on the expression of PEPT1 and pharmacokinetics upon acute hypoxia at high altitude in rat. Acta Pharmacol. Sin., 2017, 52(11), 1715-1721.
[64]
Luo, B.; Li, J.; Yang, T.; Li, W.; Zhang, J.; Wang, C.; Zhao, A.; Wang, R. Evaluation of renal excretion and pharmacokinetics of furosemide in rats after acute exposure to high altitude at 4300 m. Biopharm. Drug Dispos., 2018, 39(8), 378-387.
[http://dx.doi.org/10.1002/bdd.2154] [PMID: 30120768]
[65]
Huang, L.J. Study on Pharmacokinetic Characteristics and Influential Factors of Common Hypoglycemic Drugs under High Altitude Hypoxia Enviroment. Lanzhou University. PA, 2021. https://kns.cnki.net/kcms2/article/abstract?v=3uoqIhG8C475KOm_zr gu4lQARvep2SAkOTSE1G1uB0_um8HHdEYmZkE8NpB59kRm0Sj URhA4QAB2Uc16Ea1gb_vr_krjEOHR&uniplatform=NZKPT.
[66]
Yue, X.R. The Study of DNA Methylation Regulates Drug Transporter Gene Transcription under Hypoxic Condition. Lanzhou University. PA, 2019 https://kns.cnki.net/kcms2/article/abstract?v=3uoqIhG8C475KOm_zr gu4lQARvep2SAkOTSE1G1uB0_um8HHdEYmZmYmILeUG8l9sb wmuA4FHTUQuRA0-lFMDrSupeHOOjZw&uniplatform=NZKPT.

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