Table 1.
Patient Demographics and Biochemical Values.
Table 2.
Distribution of Exonic Keratin Variants.
Table 3.
Distribution of Non-Coding Keratin Variants.
Table 4.
The Clinical Features of Hemochromatosis Patients Harboring Exonic and Intronic Keratin 8 Variants.
Figure 1.
The K8 G62C variant does not influence the extent of hepatocellular iron accumulation.
To test, whether hepatocellular iron accumulation is affected by the presence of keratin variants, transgenic mice overexpressing wild-type human keratin 8 (K8 WT) or K8 G62C variant were fed with 3% carbonyl iron-containing diet for one month (Iron) and compared to age-matched animals kept on standard diet (Control) (n = 4 mice/group). Iron-feeding did not lead to an increase in serum ALT (A), but caused a significant elevation in hepatic iron concentration (HIC) (B). There was no significant difference in ALT or HIC levels between K8 WT and G62C mice after iron feeding. (C) Perl's Prussian blue staining revealed a similar pattern of iron deposition in both mouse lines. Scale bar = 200 µm.
Figure 2.
The K8 G62C variant does not affect iron toxicity in ex vivo cultured hepatocytes.
To study the hepatocellular iron toxicity, primary hepatocytes from transgenic animals overexpressing K8 WT or K8 G62C were cultured in normal media (Control) or media supplemented with 100 µM nitrilotriacetic acid (NTA) or 100 µM iron-NTA (FeNTA) for 24 hours. FeNTA, but not NTA treatment led to a significant increase in LDH (A) and ALT levels (C) in cell culture supernatants together with significant decrease in cell viability as assessed by MTT assay (B). The enzyme levels and cell viability did not differ significantly between K8 WT and K8 G62C hepatocytes.