1.

Chemical chaperones protect epidermolysis bullosa simplex keratinocytes from heat stress-induced keratin aggregation : involvement of heat shock proteins and MAP kinases

In this study, the effects of heat stress on keratin aggregation in immortalized cells from two patients with EBS (KRT5) and a healthy control were examined with and without addition of various test compounds. Heat-induced (43 °C, 30 minutes) aggregates were observed in all cell lines, the amount of which correlated with the donor phenotype. In EBS cells pre-exposed to proteasome inhibitor, MG132, and p38-mitogen-activated protein kinase (MAPK) inhibitor, SB203580, the proportion of aggregate-positive cells increased, suggesting a role of proteasomes and phosphorylation in removing mutated keratin. In contrast, aggregates were reduced by pretreatment with two chemical chaperones, trimethylamine N-oxide (TMAO) and 4-phenylbutyrate (4-PBA). TMAO also modulated stress-induced p38/c-jun N-terminal kinase (JNK) activation and expression of heat shock protein (HSPA1A), the latter of which colocalized with phosphorylated keratin 5 in EBS cells. Taken together, our findings suggest therapeutic targets for EBS and other keratinopathies.

COBISS.SI-ID: 28273369

2.

The consequences of keratin gene mutations in epidermolysis bullosa simplex (EBS) keratinocytes grown in culture are influenced by growth conditions

We show direct examples and discuss the importance of cell culture conditions to the end result of cell-based assays

COBISS.SI-ID: 29227481