Expression of the iron-regulatory protein haemojuvelin in retina and its regulation during cytomegalovirus infection

Jaya Pranava Gnana-Prakasam, Ming Zhang, Pamela Moore Martin, Sally S. Atherton, Sylvia B Smith, Vadivel Ganapathy

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Haemochromatosis is a genetic disorder of iron overload resulting from loss-of-function mutations in genes coding for the iron-regulatory proteins HFE [HLA-like protein involved in iron (Fe) homoeostasis], transferrin receptor 2, ferroportin, hepcidin and HJV (haemojuvelin). Expression of the first four genes coding for these proteins in retina has been established. Here we report on the expression of HJV. Since infection of retina with CMV (cytomegalovirus) causes blindness, we also investigated the expression of HJV and other iron-regulatory proteins in retina during CMV infection. HJV (HJV gene) mRNA was expressed in RPE (retinal pigment epithelium)/eyecup and neural retina in mouse. In situ hybridization and immunohistochemistry confirmed the presence of HJV mRNA and protein in RPE, outer and inner nuclear layers, and ganglion cell layer. Immunocytochemistry with cell lines and primary cell cultures showed HJV expression in RPE and Müller cells. In RPE, the expression was restricted to apical membrane. Infection of primary cultures of mouse RPE with CMV increased HJV mRNA and protein levels. Under similar conditions, HFE (HFE gene) mRNA levels were not altered, but HFE protein was decreased. Hepcidin expression was, however, not altered. These findings were demonstrable in vivo with CMV-infected mouse retina. The CMV-induced up-regulation of HJV in RPE was independent of changes in HFE because the phenomenon was also seen in HFE-null RPE cells. CMV-infected primary RPE cells showed evidence of iron accumulation and oxidative stress, as indicated by increased levels of ferritin and hydroxynonenal. The observed changes in HJV expression and iron status during CMV infection in retina may have significance in the pathophysiology of CMV retinitis.

Original languageEnglish (US)
Pages (from-to)533-543
Number of pages11
JournalBiochemical Journal
Volume419
Issue number3
DOIs
StatePublished - May 1 2009

Fingerprint

Iron-Regulatory Proteins
Retinal Pigments
Retinal Pigment Epithelium
Cytomegalovirus Infections
Retina
Cytomegalovirus
Iron
Genes
Hepcidins
Messenger RNA
Proteins
Immunohistochemistry
Cells
Cytomegalovirus Retinitis
Muromegalovirus
Inborn Genetic Diseases
Transferrin Receptors
Iron Overload
Oxidative stress
Primary Cell Culture

Keywords

  • Cytomegalovirus (CMV)
  • Haemochromatosis
  • Haemojuvelin (HJV)
  • Müller cell
  • Retina
  • Retinal pigment epithelium

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Expression of the iron-regulatory protein haemojuvelin in retina and its regulation during cytomegalovirus infection. / Gnana-Prakasam, Jaya Pranava; Zhang, Ming; Martin, Pamela Moore; Atherton, Sally S.; Smith, Sylvia B; Ganapathy, Vadivel.

In: Biochemical Journal, Vol. 419, No. 3, 01.05.2009, p. 533-543.

Research output: Contribution to journalArticle

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abstract = "Haemochromatosis is a genetic disorder of iron overload resulting from loss-of-function mutations in genes coding for the iron-regulatory proteins HFE [HLA-like protein involved in iron (Fe) homoeostasis], transferrin receptor 2, ferroportin, hepcidin and HJV (haemojuvelin). Expression of the first four genes coding for these proteins in retina has been established. Here we report on the expression of HJV. Since infection of retina with CMV (cytomegalovirus) causes blindness, we also investigated the expression of HJV and other iron-regulatory proteins in retina during CMV infection. HJV (HJV gene) mRNA was expressed in RPE (retinal pigment epithelium)/eyecup and neural retina in mouse. In situ hybridization and immunohistochemistry confirmed the presence of HJV mRNA and protein in RPE, outer and inner nuclear layers, and ganglion cell layer. Immunocytochemistry with cell lines and primary cell cultures showed HJV expression in RPE and M{\"u}ller cells. In RPE, the expression was restricted to apical membrane. Infection of primary cultures of mouse RPE with CMV increased HJV mRNA and protein levels. Under similar conditions, HFE (HFE gene) mRNA levels were not altered, but HFE protein was decreased. Hepcidin expression was, however, not altered. These findings were demonstrable in vivo with CMV-infected mouse retina. The CMV-induced up-regulation of HJV in RPE was independent of changes in HFE because the phenomenon was also seen in HFE-null RPE cells. CMV-infected primary RPE cells showed evidence of iron accumulation and oxidative stress, as indicated by increased levels of ferritin and hydroxynonenal. The observed changes in HJV expression and iron status during CMV infection in retina may have significance in the pathophysiology of CMV retinitis.",
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AU - Gnana-Prakasam, Jaya Pranava

AU - Zhang, Ming

AU - Martin, Pamela Moore

AU - Atherton, Sally S.

AU - Smith, Sylvia B

AU - Ganapathy, Vadivel

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