Chronic Variable Stress Induces Hepatic Fe(II) Deposition by Up-Regulating ZIP14 Expression Via MiR-181 Family Pathway in Rats

Overview

Journal Biology (Basel)

Publisher MDPI

Specialty Biology

Date 2021 Aug 6

PMID 34356508

Citations 3

Authors

Shuxia Jiang

Taining Guo

Shihui Guo

Jiang Gao

Yingdong Ni

Wenqiang Ma

Ruqian Zhao

Affiliations

Soon will be listed here.

Abstract

It is well-known that hepatic iron dysregulation, which is harmful to health, can be caused by stress. The aim of the study was to evaluate chronic variable stress (CVS) on liver damage, hepatic ferrous iron deposition and its molecular regulatory mechanism in rats. Sprague Dawley rats at seven weeks of age were randomly divided into two groups: a control group (Con) and a CVS group. CVS reduces body weight, but increases the liver-to-body weight ratio. The exposure of rats to CVS increased plasma aspartate aminotransferase (AST), alkaline phosphatase (ALP) and hepatic malondialdehyde (MDA) levels, but decreased glutathione peroxidase (GSH-Px) activity, resulting in liver damage. CVS lowered the total amount of hepatic iron content, but induced hepatic Fe(II) accumulation. CVS up-regulated the expression of transferrin receptor 1 (TFR1) and ZRT/IRT-like protein 14 (ZIP14), but down-regulated ferritin and miR-181 family members. In addition, miR-181 family expression was found to regulate ZIP14 expression in HEK-293T cells by the dual-luciferase reporter system. These results indicate that CVS results in liver damage and induces hepatic Fe(II) accumulation, which is closely associated with the up-regulation of ZIP14 expression via the miR-181 family pathway.

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References

Coffey R, Knutson M . The plasma membrane metal-ion transporter ZIP14 contributes to nontransferrin-bound iron uptake by human β-cells. Am J Physiol Cell Physiol. 2016; 312(2):C169-C175. PMC: 5336597. DOI: 10.1152/ajpcell.00116.2016. View

Jiang S, Fang X, Liu M, Ni Y, Ma W, Zhao R . MiR-20b Down-Regulates Intestinal Ferroportin Expression In Vitro and In Vivo. Cells. 2019; 8(10). PMC: 6829237. DOI: 10.3390/cells8101135. View

Gonzalez-Torres M, Dos Santos C . Uncontrollable chronic stress affects eating behavior in rats. Stress. 2019; 22(4):501-508. DOI: 10.1080/10253890.2019.1596079. View

Farina M, Avila D, da Rocha J, Aschner M . Metals, oxidative stress and neurodegeneration: a focus on iron, manganese and mercury. Neurochem Int. 2012; 62(5):575-94. PMC: 3615063. DOI: 10.1016/j.neuint.2012.12.006. View

Kopec R, Caris-Veyrat C, Nowicki M, Bernard J, Morange S, Chitchumroonchokchai C . The Effect of an Iron Supplement on Lycopene Metabolism and Absorption During Digestion in Healthy Humans. Mol Nutr Food Res. 2019; 63(22):e1900644. DOI: 10.1002/mnfr.201900644. View

Bloomer S, Brown K, Buettner G, Kregel K . Dysregulation of hepatic iron with aging: implications for heat stress-induced oxidative liver injury. Am J Physiol Regul Integr Comp Physiol. 2008; 294(4):R1165-74. DOI: 10.1152/ajpregu.00719.2007. View

Babu K, Muckenthaler M . miR-148a regulates expression of the transferrin receptor 1 in hepatocellular carcinoma. Sci Rep. 2019; 9(1):1518. PMC: 6365501. DOI: 10.1038/s41598-018-35947-7. View

Ali F, Rifaai R . Preventive effect of omega-3 fatty acids in a rat model of stress-induced liver injury. J Cell Physiol. 2018; 234(7):11960-11968. DOI: 10.1002/jcp.27848. View

Yang J, Zhu A, Xiao S, Zhang T, Wang L, Wang Q . Anthraquinones in the aqueous extract of Cassiae semen cause liver injury in rats through lipid metabolism disorder. Phytomedicine. 2019; 64:153059. DOI: 10.1016/j.phymed.2019.153059. View

10.

Herbet M, Korga A, Gawronska-Grzywacz M, Izdebska M, Piatkowska-Chmiel I, Poleszak E . Chronic Variable Stress Is Responsible for Lipid and DNA Oxidative Disorders and Activation of Oxidative Stress Response Genes in the Brain of Rats. Oxid Med Cell Longev. 2017; 2017:7313090. PMC: 5612311. DOI: 10.1155/2017/7313090. View

11.

Liu Z, Wang S, Li W, Tian Y . Bioimaging and Biosensing of Ferrous Ion in Neurons and HepG2 Cells upon Oxidative Stress. Anal Chem. 2018; 90(4):2816-2825. DOI: 10.1021/acs.analchem.7b04934. View

12.

Lawen A, Lane D . Mammalian iron homeostasis in health and disease: uptake, storage, transport, and molecular mechanisms of action. Antioxid Redox Signal. 2012; 18(18):2473-507. DOI: 10.1089/ars.2011.4271. View

13.

Aydemir T, Cousins R . The Multiple Faces of the Metal Transporter ZIP14 (SLC39A14). J Nutr. 2018; 148(2):174-184. PMC: 6251594. DOI: 10.1093/jn/nxx041. View

14.

Pietrangelo A . Iron and the liver. Liver Int. 2016; 36 Suppl 1:116-23. DOI: 10.1111/liv.13020. View

15.

Garrick L, Dolan K, Romano M, Garrick M . Non-transferrin-bound iron uptake in Belgrade and normal rat erythroid cells. J Cell Physiol. 1999; 178(3):349-58. DOI: 10.1002/(SICI)1097-4652(199903)178:3<349::AID-JCP9>3.0.CO;2-R. View

16.

Tang Y, Li Y, Yu H, Gao C, Liu L, Xing M . Quercetin attenuates chronic ethanol hepatotoxicity: implication of "free" iron uptake and release. Food Chem Toxicol. 2014; 67:131-8. DOI: 10.1016/j.fct.2014.02.022. View

17.

Meister G . miRNAs get an early start on translational silencing. Cell. 2007; 131(1):25-8. DOI: 10.1016/j.cell.2007.09.021. View

18.

Friedman R, Farh K, Burge C, Bartel D . Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2008; 19(1):92-105. PMC: 2612969. DOI: 10.1101/gr.082701.108. View

19.

Wang X, Che H, Zhang W, Wang J, Ke T, Cao R . Effects of Mild Chronic Intermittent Cold Exposure on Rat Organs. Int J Biol Sci. 2015; 11(10):1171-80. PMC: 4551753. DOI: 10.7150/ijbs.12161. View

20.

Jiang S, Guo S, Li H, Ni Y, Ma W, Zhao R . Identification and Functional Verification of MicroRNA-16 Family Targeting Intestinal Divalent Metal Transporter 1 (DMT1) and . Front Physiol. 2019; 10:819. PMC: 6610423. DOI: 10.3389/fphys.2019.00819. View