In this study we have performed genome-wide analysis to identify Nkx2-5 binding regions using mid-gestation mouse hearts to gain insight into the molecular mechanisms by which Nkx2-5 contributes to the correct development of the heart. Nkx2-5 and SRF invivo binding sites were mapped using ChIPchip assays and analysis of the ChIP-chip data has identified 600 and 858 SRF and Nkx2-5-binding sites,...

Niemann Pick type C (NP-C) is a rare neurodegenerative disorder caused by an impairment of intracellular lipid transport. Due to the heterogeneous clinical phenotype and the lack of a reliable blood test, diagnosis and therapy are often delayed for years. In the cell, accumulating cholesterol leads to increased formation of oxysterols that can be used as a powerful screening parameter for NP-C....

Ursodeoxycholic acid (UDCA) is used to treat liver diseases and demonstrates cardioprotective effects. Accumulation of the plasma membrane sphingolipid sphingomyelin in the heart can lead to atherosclerosis and coronary artery disease. Sphingomyelinases (SMases) break down sphingomyelin, producing ceramide, and inhibition of SMases activity can promote cell survival. We hypothesized that UDCA r...

The Niemann-Pick disease group is now divided into two distinct entities: (1) acid sphingomyelinase-deficient Niemann-Pick disease (ASM-deficient NPD) resulting from mutations in the SMPD1 gene and encompassing type A and type B as well as intermediate forms; (2) Niemann-Pick disease type C (NP-C) including also type D, resulting from mutations in either the NPC1 or the NPC2 gene. Both Niemann-...

Metastatic dissemination of cancer cells is the ultimate hallmark of malignancy and accounts for approximately 90% of human cancer deaths. We investigated the role of acid sphingomyelinase (Asm) in the hematogenous metastasis of melanoma cells. Intravenous injection of B16F10 melanoma cells into wild-type mice resulted in multiple lung metastases, while Asm-deficient mice (Smpd1(-/-) mice) were...

In this study we have performed genome-wide analysis to identify Nkx2-5 binding regions using mid-gestation mouse hearts to gain insight into the molecular mechanisms by which Nkx2-5 contributes to the correct development of the heart. Nkx2-5 and SRF invivo binding sites were mapped using ChIPchip assays and analysis of the ChIP-chip data has identified 600 and 858 SRF and Nkx2-5-binding sites,...

Aim. To assess gene expression of enzymes the sphingomyelinase pathway ceramide biosynthesis and degradation in fat depots various localization patients with cardiovascular diseases. Material methods. A total 38 were examined: 20 coronary artery disease (CAD) 18 aortic stenosis/insufficiency. Biopsies subcutaneous, epicardial, perivascular adipose tissue (AT) (SAT, EAT, PVAT, respectively) obta...

Keratins are epithelial cell intermediate filament (IF) proteins that are expressed as pairs in a cell-differentiation-regulated manner. Hepatocytes express the keratin 8 and 18 pair (denoted K8/K18) of IFs, and a loss of K8 or K18, as in K8-null mice, leads to degradation of the keratin partner. We have previously reported that a K8/K18 loss in hepatocytes leads to altered cell surface lipid r...