geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Loss of Hfe leads to progression of tumor phenotype in primary retinal pigment epithelial cells


, : Loss of Hfe leads to progression of tumor phenotype in primary retinal pigment epithelial cells. Investigative Ophthalmology & Visual Science 54(1): 63-71

Hemochromatosis is a disorder of iron overload arising mostly from mutations in HFE. HFE is expressed in retinal pigment epithelium (RPE), and Hfe(-/-) mice develop age-related iron accumulation and retinal degeneration associated with RPE hyperproliferation. Here, the mechanism underlying the hyperproliferative phenotype in RPE was investigated. Cellular senescence was monitored by β-galactosidase activity. Gene expression was monitored by real-time PCR. Survivin was analyzed by Western blot and immunofluorescence. Migration and invasion were monitored using appropriate kits. Glucose transporters (GLUTs) were monitored by 3-O-methyl-D-glucose uptake. Histone deacetylases (HDACs) were studied by monitoring catalytic activity and acetylation status of histones H3/H4. Hfe(-/-) RPE cells exhibited slower senescence rate and higher survivin expression than wild type cells. Hfe(-/-) cells migrated faster and showed greater glucose uptake and increased expression of GLUTs. The expression of HDACs and DNA methyltransferase (DNMTs) also was increased. Similarly, RPE cells from hemojuvelin (Hjv)-knockout mice, another model of hemochromatosis, also had increased expression of GLUTs, HDACs, and DNMTs. The expression of Slc5a8 was decreased in Hfe(-/-) RPE cells, but treatment with a DNA methylation inhibitor restored the transporter expression, indicating involvement of DNA methylation in the silencing of Slc5a8 in Hfe(-/-) cells. RPE cells from iron-overloaded mice exhibit several features of tumor cells: decreased senescence, enhanced migration, increased glucose uptake, and elevated levels of HDACs and DNMTs. These features are seen in Hfe(-/-) RPE cells as well as in Hjv(-/-) RPE cells, providing a molecular basis for the hyperproliferative phenotype of Hfe(-/-) and Hjv(-/-) RPE cells.

US$19.90

PMID: 23169885

DOI: 10.1167/iovs.12-10312


Other references

Schoch, Thomas J., 1965: Starch in bakery products. Bakers Dig 39(2): 48-57

Montague, D.K., 1993: Treatment of erectile dysfunction. Journal of Urology 150(6): 1833-1833

van Kerchove, C., 1970: Application of polarography in the drug field. Journal de Pharmacie de Belgique 25(3): 215-246

Slein, P.K.; Domitrovich, P.P.; Kleiger, R.E.; Rottman, J.N., 1997: Heart rate variability after treatment with type Ic antiarrhythmics predicts mortality in CAST. Circulation 96(8 SUPPL ): I716, 10/21/97

Díez, M.; Sánchez, E.; García López, S.; Arroyo, Mía.Teresa.; Gomollón, F., 2007: Infliximab therapy in ulcerative colitis: initial experience in two referral centers. To perform a descriptive analysis of our experience with infliximab in the treatment of ulcerative colitis (UC). We performed a retrospective, observational study of all patients with UC treated with infliximab and with criteria of corticosteroid...

Wadhwa S.; Gopinath G., 1979: Glial cell differentiation in the cerebral cortex of the rat during post natal period. Journal of the Anatomical Society of India 28(1): 61-62

Aizenverh, D.E., 1963: Stratigrafiya kamennougol'nuikh otlozenii Donelskogo Basseina. Trud Inst geol Nauk Akad Ukran SSR Strat Paleont, 37: 1-182

Subramaniam, R.; Kouriefs, C.; Dickson, A.P., 1999: Antenatally detected pelvi-ureteric junction obstruction: Concerns about conservative management. Objective To review the conservative management of antenatally detected pelvi-ureteric junction (PUJ) obstruction in children. Patients and methods The study included 121 children (142 kidneys) with antenatally diagnosed PUJ obstruction managed ov...

Kondratyuk, S.Ya, 1994: Lichen indication mapping of air pollution in Ukraine. This study aims at estimating the state of atmospheric air in industrial areas of the Ivano-Frankivs'k region on the basis of lichen indication mapping. The distribution of the lichen species or groups of species with similar sensitivity to a...

Theall, K.P.; DeJong, W.; Scribner, R.; Mason, K.; Schneider, S.Kessel.; Simonsen, N., 2010: Social capital in the college setting: the impact of participation in campus activities on drinking and alcohol-related harms. The authors aimed to replicate previous findings on social capital and harmful alcohol outcomes in the college setting and to ascertain the protective effects of additional indicators of social capital. Over 4 years (2000-2004), the authors conduc...