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We have previously shown that compatible organic osmolytes, such as betaine, myo-inositol and taurine, are part of the stress response of normal human keratinocytes (NHKs) to ultraviolet B (UVB) radiation. In this regard, we tested human HaCaT keratinocytes as a surrogate cell line for NHK. HaCaT cells osmo-dependently express mRNA specific for transport proteins for betaine (BGT-1), myo-inositol (SMIT) and taurine (TAUT). Compared to normoosmotic (305 mosmol/l) controls, which strongly constitutively expressed BGT-1 mRNA, strong induction of SMIT and TAUT mRNA as well as low induction of BGT-1 mRNA expression was observed between 3 and 9 h after hyperosmotic exposure (405 mosmol/l). This expression correlated with an increased osmolyte uptake. Conversely, hypoosmotic (205 mosmol/l) stimulation led to a significant efflux of osmolytes. Exposure to UVB (290–315 nm) radiation induced cell shrinkage which was followed by an upregulation of osmolyte transporter mRNA levels and osmolyte uptake. These results demonstrate that human HaCaT keratinocytes possess an osmolyte strategy including UVB-induced cell shrinkage and following increased osmolyte uptake. However, several differences in osmolyte transporter expression and uptake were noted between NHK and HaCaT cells, indicating that the use of HaCaT cells as a surrogate cell line for NHK has limitations. [ABSTRACT FROM AUTHOR]

Taurine is the most abundant free amino acid in heart muscle and protects against heart failure. In the present study, the consequences of hereditary taurine deficiency on cardiac gene expression were examined in 2- and 15–16-month-old taurine transporter knockout ( taut-/-) mice using a mouse-specific DNA microarray. This oligonucleotide-based microarray contains probes for 251 genes with relevance for heart function. Of these, 163 probes exhibited a reproducible hybridization signal and were analyzed. α-Actin type 1 mRNA levels were 70% lower in the heart of young and older taut-/- mice compared to wild-type controls. Interestingly, the hearts of taut-/- mice showed a switch from α-actin 1 to α-actin 2 expression, as confirmed by real-time PCR and Western blot analysis. In addition, mRNA levels of biomarkers for pressure overload and hypertension were upregulated in taut-/- hearts, i.e., atrial natriuretic factor (+848%), brain natriuretic peptide (+90%), cardiac ankyrin repeat protein (+118%), and procollagen 1a1, 1a2 and 3a1 (+40% at least). These results point to a stress situation in the heart of taut-/- mice under laboratory conditions, and it can be speculated that taut-/- hearts may be even more susceptible to failure in the wild when under exogenous stress. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS) induces hepatocellular down-regulation and endocytic retrieval of multidrug resistance protein 2 (Mrp2, Abcc2). Basolateral Mrp isoforms may compensate for the intracellular metabolic changes in cholestasis. Therefore, the effect of LPS on the zonal localization of Mrp2 and Mrp3 and the expression of Mrp3, Mrp4, Mrp5, and Mrp6 mRNA were investigated in rat liver. In normal rat liver Mrp3 was found in pericentral hepatocytes also expressing glutamine synthetase. In LPS-treated rat liver the decrease in Mrp2 protein was most pronounced in pericentral hepatocytes, with only minor down-regulation in periportal hepatocytes. Conversely, induction of Mrp3 was found in pericentral hepatocytes with a low expression of Mrp2. Furthermore, we found a strong induction of Mrp5 mRNA. Likewise, Mrp6 mRNA was up-regulated, however Mrp6 protein expression was not significantly altered. It is concluded that Mrp3 is inversely regulated to Mrp2 in a zonal pattern and may compensate for the LPS-induced loss of Mrp2 in the perivenous area. Induction of pericentral Mrp3 and up-regulation of Mrp5 mRNA may play an important role in the hepatocellular clearance of cholephilic substances and cyclic nucleotides accumulating after LPS treatment. [ABSTRACT FROM AUTHOR]