Hepatocyte Growth Factor Protects PC12 Cells Against OGD/R-induced Injury by Reducing Iron

Overview

Journal Biosci Rep

Specialty Cell Biology

Date 2020 Mar 19

PMID 32186328

Citations 1

Authors

Siyue Li

Zhong-Ming Qian

Gaojing Xu

Jie Zheng

Yi Wu

Affiliations

Soon will be listed here.

Abstract

In the light of hepatocyte growth factor (HGF) the inhibiting role on the expression of hepcidin, we hypothesized that HGF might be able to reduce cell and tissue iron by increasing ferroportin 1 (Fpn1) content and Fpn1-mediated iron release from cells and tissues. The hypothesized ability of HGF to reduce iron might be one of the mechanisms associated with its neuroprotective action under the conditions of ischemia/reperfusion (I/R). Here, we investigated the effects of HGF on the expression of hepcidin as well as transferrin receptor 1 (TfR1), divalent metal transporter 1 (DMT1), Fpn1, ferritin and iron regulatory proteins (IRPs) in oxygen-glucose deprivation and reoxygenation (OGD/R)-treated PC12 cells by real-time PCR and Western blot analysis. We demonstrated that HGF could completely reverse the OGD/R-induced reduction in Fpn1 and IRP1 expression and increase in ferritin light chain protein and hepcidin mRNA levels in PC12 cells. It was concluded that HGF protects PC12 cells against OGD/R-induced injury mainly by reducing cell iron contents via the up-regulation of Fpn1 and increased Fpn1-mediated iron export from cells. Our findings suggested that HGF may also be able to ameliorate OGD/R or I/R-induced overloading of brain iron by promoting Fpn1 expression.

Citing Articles

Exploring the Causal Relationship Between Inflammatory Cytokines and MRI-Derived Brain Iron: A Mendelian Randomization Study.

Wu Z, Xu W, Wang X, Peng D, Jiang Z Brain Behav. 2024; 14(12):e70181.

PMID: 39643932 PMC: 11624122. DOI: 10.1002/brb3.70181.

References

Qian Z, Ke Y . Hepcidin and its therapeutic potential in neurodegenerative disorders. Med Res Rev. 2019; 40(2):633-653. DOI: 10.1002/med.21631. View

Nakamura T, Sakai K, Nakamura T, Matsumoto K . Hepatocyte growth factor twenty years on: Much more than a growth factor. J Gastroenterol Hepatol. 2011; 26 Suppl 1:188-202. DOI: 10.1111/j.1440-1746.2010.06549.x. View

Torti F, Torti S . Regulation of ferritin genes and protein. Blood. 2002; 99(10):3505-16. DOI: 10.1182/blood.v99.10.3505. View

Date I, Takagi N, Takagi K, Kago T, Matsumoto K, Nakamura T . Hepatocyte growth factor attenuates cerebral ischemia-induced learning dysfunction. Biochem Biophys Res Commun. 2004; 319(4):1152-8. DOI: 10.1016/j.bbrc.2004.05.100. View

Qian Z, Wang Q . Expression of iron transport proteins and excessive iron accumulation in the brain in neurodegenerative disorders. Brain Res Brain Res Rev. 1998; 27(3):257-67. DOI: 10.1016/s0165-0173(98)00012-5. View

He W, Qian Zhong M, Zhu L, Christopher Q, Du F, Yung W . Ginkgolides mimic the effects of hypoxic preconditioning to protect C6 cells against ischemic injury by up-regulation of hypoxia-inducible factor-1 alpha and erythropoietin. Int J Biochem Cell Biol. 2007; 40(4):651-62. DOI: 10.1016/j.biocel.2007.10.013. View

Gallo S, Sala V, Gatti S, Crepaldi T . HGF/Met Axis in Heart Function and Cardioprotection. Biomedicines. 2017; 2(4):247-262. PMC: 5344277. DOI: 10.3390/biomedicines2040247. View

Hentze M, Muckenthaler M, Galy B, Camaschella C . Two to tango: regulation of Mammalian iron metabolism. Cell. 2010; 142(1):24-38. DOI: 10.1016/j.cell.2010.06.028. View

Wang Q, Du F, Qian Z, Ge X, Zhu L, Yung W . Lipopolysaccharide induces a significant increase in expression of iron regulatory hormone hepcidin in the cortex and substantia nigra in rat brain. Endocrinology. 2008; 149(8):3920-5. PMC: 2488231. DOI: 10.1210/en.2007-1626. View

10.

Du F, Qian Z, Zhu L, Wu X, Yung W, Tsim T . L-DOPA neurotoxicity is mediated by up-regulation of DMT1-IRE expression. PLoS One. 2009; 4(2):e4593. PMC: 2643485. DOI: 10.1371/journal.pone.0004593. View

11.

Yu S, Yuan L, Yang X, Wang K, Ke Y, Qian Z . La3+-promoted proliferation is interconnected with apoptosis in NIH 3T3 cells. J Cell Biochem. 2004; 94(3):508-19. DOI: 10.1002/jcb.20303. View

12.

Lawson D, Treffry A, Artymiuk P, Harrison P, Yewdall S, Luzzago A . Identification of the ferroxidase centre in ferritin. FEBS Lett. 1989; 254(1-2):207-10. DOI: 10.1016/0014-5793(89)81040-3. View

13.

Niimura M, Takagi N, Takagi K, Mizutani R, Ishihara N, Matsumoto K . Prevention of apoptosis-inducing factor translocation is a possible mechanism for protective effects of hepatocyte growth factor against neuronal cell death in the hippocampus after transient forebrain ischemia. J Cereb Blood Flow Metab. 2006; 26(11):1354-65. DOI: 10.1038/sj.jcbfm.9600287. View

14.

Nemeth E, Ganz T . Regulation of iron metabolism by hepcidin. Annu Rev Nutr. 2006; 26:323-42. DOI: 10.1146/annurev.nutr.26.061505.111303. View

15.

Maina F, Klein R . Hepatocyte growth factor, a versatile signal for developing neurons. Nat Neurosci. 1999; 2(3):213-7. DOI: 10.1038/6310. View

16.

Ganz T, Nemeth E . Hepcidin and disorders of iron metabolism. Annu Rev Med. 2010; 62:347-60. DOI: 10.1146/annurev-med-050109-142444. View

17.

Qian Z, Tang P, Wang Q . Iron crosses the endosomal membrane by a carrier-mediated process. Prog Biophys Mol Biol. 1997; 67(1):1-15. DOI: 10.1016/s0079-6107(97)00009-6. View

18.

Carbonell T, Rama R . Iron, oxidative stress and early neurological deterioration in ischemic stroke. Curr Med Chem. 2007; 14(8):857-74. DOI: 10.2174/092986707780363014. View

19.

Miyazawa K, Tsubouchi H, Naka D, Okigaki M, Arakaki N, Nakayama H . Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor. Biochem Biophys Res Commun. 1989; 163(2):967-73. DOI: 10.1016/0006-291x(89)92316-4. View

20.

Lipscomb D, Gorman L, Traystman R, Hurn P . Low molecular weight iron in cerebral ischemic acidosis in vivo. Stroke. 1998; 29(2):487-92; discussion 493. DOI: 10.1161/01.str.29.2.487. View