Fatty acids induce hepatocyte senescence in vitro: implications for pathogenesis in non-alcoholic steatohepatitis

Skoien, R., Powell, E. E., Melino, M., Clouston, A. D., Gabrielli, B. G. and Jonsson, J. R. (2010). Fatty acids induce hepatocyte senescence in vitro: implications for pathogenesis in non-alcoholic steatohepatitis. In: Australian Gastroenterology Week 2010. Australian Gastroenterology Week 2010, Gold Coast, QLD, Australia, (A13-A14). 20-23 October 2010. doi:10.1111/j.1440-1746.2010.06450.x


Author Skoien, R.
Powell, E. E.
Melino, M.
Clouston, A. D.
Gabrielli, B. G.
Jonsson, J. R.
Title of paper Fatty acids induce hepatocyte senescence in vitro: implications for pathogenesis in non-alcoholic steatohepatitis
Formatted title
Fatty acids induce hepatocyte senescence in vitro: implications for pathogenesis in non-alcoholic steatohepatitis
Conference name Australian Gastroenterology Week 2010
Conference location Gold Coast, QLD, Australia
Conference dates 20-23 October 2010
Proceedings title Australian Gastroenterology Week 2010   Check publisher's open access policy
Journal name Journal of Gastroenterology and Hepatology   Check publisher's open access policy
Place of Publication Richmond, VIC, Australia
Publisher Wiley-Blackwell Publishing
Publication Year 2010
Sub-type Published abstract
DOI 10.1111/j.1440-1746.2010.06450.x
ISSN 0815-9319
1440-1746
Volume 25
Issue Suppl. 3
Start page A13
End page A14
Total pages 2
Language eng
Formatted Abstract/Summary
Introduction Hereditary iron overload associated with mutations in the
Ferroportin gene produce a dichotomy of phenotypes resulting from either
an increase or decrease in iron effl ux capacity. In this study we examined
the molecular basis of iron overload in an Australian family of Vietnamese
origin, characterised the molecular and cellular defect, and correlated this
with the clinical and pathological phenotype.
Methods We analysed the Ferroportin gene by DNA sequencing. Liver
biopsy was performed on two members of the family. Molecular characterisation
was performed by immunofl uorescence microscopy analysis of
transfected liver, kidney and intestinal cell lines. We analysed the ferritin
levels of cells expressing wild-type and mutant ferroportin to defi ne the
nature of the molecular defect on iron transport.
Results We identifi ed a G to A nucleotide change at position 238 in the
Ferroportin gene leading to the G80S substitution in family members from
three different generations. These patients presented with hyperferritinemia
in the presence of normal transferrin saturation. Perls’ staining of
liver sections showed a marked presence of iron throughout the parenchyma.
Stainable iron was present in Kupffer cells with signifi cant staining
in the periportal hepatocytes. Cellular analysis of the mutant protein indicates
that this amino acid change does not affect the localisation of the
protein but does affect its ability to transport iron.
Conclusions This is the fi rst clinical report of ferroportin disease in a
family of Vietnamese origin and the fi rst report of the G80S ferroportin
mutation outside of Southern Europe. We also show that in in vitro studies
the G80S mutant ferroportin fails to export iron. This is in agreement with
the phenotypic characteristics of patients carrying this mutation which are
indicative of the classical form of ferroportin disease which is characterised
by hyperferritinemia with normal transferrin saturation, and iron
accumulation preferentially in macrophages.
Q-Index Code CX
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Special Issue: Australian Gastroenterology Week 2010. Published under Basic Science.

Document type: Conference Paper
Collections: School of Medicine Publications
UQ Diamantina Institute Publications
 
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