Niemann-Pick-A/B disease is a lysosomal storage disease caused by deficiency of acid sphingomyelinase (1 ). Efforts are underway to develop novel therapies for this disease, and some newborn screening centers have started to test for acid sphingomyelinase enzymatic activity in dried blood spots on newborn screening cards. Available assays for newborn screening include tandem mass spectrometry (...

Recent evidence suggests clustering of plasma membrane rafts into ceramide-enriched platforms serves as a transmembrane signaling mechanism for a subset of cell surface receptors and environmental stresses (Grassme, H., Jekle, A., Riehle, A., Schwarz, H., Berger, J., Sandhoff, K., Kolesnick, R., and Gulbins, E. (2001) J. Biol. Chem. 276, 20589-20596; Cremesti, A., Paris, F., Grassme, H., Holler...

Hirota, Simon, Nancy Trimble, Evi Pertens, and Luke J. Janssen. Intracellular Cl fluxes play a novel role in Ca handling in airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 290: L1146–L1153, 2006. First published January 20, 2006; doi:10.1152/ajplung.00393.2005.—Intracellular Ca is actively sequestered into the sarcoplasmic reticulum (SR), whereas the release of Ca from the SR can be tr...

Human acid ceramidase was overexpressed in Chinese hamster ovary cells by amplification of the transfected, full-length cDNA. The majority of the overexpressed enzyme was secreted into the culture media and purified to apparent homogeneity. The purified protein contained the same 13-(alpha) and 40 (beta)-kDa subunits as human acid ceramidase from natural sources, had an acidic pH optimum (4.5),...

The general utility of a novel, fluorescence-based procedure for assessing gene transfer and expression has been demonstrated using hematopoietic stem and progenitor cells. Lineage-depleted hematopoietic cells were isolated from the bone marrow or fetal livers of acid sphingomyelinase-deficient mice, and retrovirally transduced with amphotropic or ecotropic vectors encoding a normal acid sphing...

NK and NKT cells play a major role in both innate immunity and in influencing the development of adaptive immune responses. CD161 (human NKR-P1A), a protein encoded in the NK gene complex, is a major phenotypic marker of both these cell types and is thought to be involved in the regulation of NK and NKT cell function. However, the mechanisms of action and signaling pathways of CD161 are poorly ...

Acid sphingomyelinase plays important roles in ceramide homeostasis, which has been proposed to be linked to insulin resistance. To test this association in vivo, acid sphingomyelinase deletion (asm(-/-)) was transferred to mice lacking the low density lipoprotein receptor (ldlr(-/-)), and then offsprings were placed on control or modified (enriched in saturated fat and cholesterol) diets for 1...

Acid sphingomyelinase deficiency (ASMD), also historically known as Niemann-Pick disease A (OMIM #257200) and B (OMIM#607616), is a rare debilitating lysosomal storage caused by pathogenic variants in SMPD1 gene. Deficient activity of the enzyme acid (ASM) leads to sphingomyelin accumulation various organs. Visceral manifestations ASMD include interstitial lung pulmonary dysfunction, splenomegal...