BACKGROUND Acid sphingomyelinase (ASM) is a key regulator of ceramide-dependent signalling pathways. Among others, activation of ASM can be induced by CD95 or cytokine signalling and by cellular stress resulting from inflammation or infection. Increased ASM activity was observed in a variety of human diseases including inflammatory and neuropsychiatric disorders. We hypothesized that basal ASM ...

TO THE EDITOR: We were delighted to note the concurrent publication of two studies linking decreased expression and function of sarcoendoplasmic reticulum Ca ATPase (SERCA) in human airway (bronchial) smooth muscle (ASM) to asthma. The first study, published in the July 2009 issue of American Journal of Physiology Lung Molecular Cellular Physiology, was actually from our group (3), whereas the ...

BACKGROUND Tuberous sclerosis complex (TSC), a tumor syndrome caused by mutations in TSC1 or TSC2 genes, is characterized by the development of hamartomas. We previously isolated, from an angiomyolipoma of a TSC2 patient, a homogenous population of smooth muscle-like cells (TSC2(-/-) ASM cells) that have a mutation in the TSC2 gene as well as TSC2 loss of heterozygosity (LOH) and consequently, ...

BACKGROUND Airway smooth muscle (ASM) contraction underlies acute bronchospasm in asthma. ASM cells can switch between a synthetic-proliferative phenotype and a contractile phenotype. While the effects of extracellular matrix (ECM) components on modulation of ASM cells to a synthetic phenotype have been reported, the role of ECM components on maturation of ASM cells to a contractile phenotype i...

Contact between airway smooth muscle (ASM) cells and activated CD4(+) T cells, a key interaction in diseases such as asthma, triggers ASM cell proliferation and enhances T cell survival. We hypothesized that direct contact between ASM and CD4(+) T cells facilitated the transfer of anti-apoptotic proteins via nanotubes, resulting in increased survival of activated CD4(+) T cells. CD4(+) T cells,...

Some organic weak bases induce a detachment from inner lysosomal membranes and subsequent inactivation of acid sphingomyelinase (ASM) and thus work as functional ASM inhibitors. The aim of the present investigation was to develop a structure-property-activity relation (SPAR) model in order to specify the structural and physicochemical characteristics of probes capable of functionally inhibiting...

Three-Dimensional (3D) Active Shape Modeling (ASM) is a straightforward extension of 2D ASM. 3D ASM is robust when true volumetric data is considered. However, when the information in one dimension is sparse, pure 3D ASM tends to be less robust. We present a hybrid 2D + 3D methodology which can deal with sparse 3D data. 2D and 3D ASMs are combined to obtain a “global optimal” segmentation of th...

Very little is known regarding the function, origin, and turnover of airway smooth muscle (ASM). In this article, we discuss the embryological development of ASM, and provide information regarding candidate mesenchymal ASM progenitor cell populations specifically in relation to airway remodeling. This review also highlights the current limitations in studying ASM biology, and underscores the ne...

This report describes the identification, cloning, and molecular analysis of Asm-1+ (Ascospore maturation 1), the Neurospora crassa homologue of the Aspergillus nidulans stuA (stunted A) gene. The Asm-1+ gene is constitutively transcribed and encodes an abundant, nucleus-localized 68.5-kD protein. The protein product of Asm-1+ (ASM-1), contains a potential DNA-binding motif present in related p...

Many receptor systems use receptor clustering for transmembrane signaling. In this study, we show that acid sphingomyelinase (ASM) is essential for the clustering of CD40. Stimulation of lymphocytes via CD40 ligation results in ASM translocation from intracellular stores, most likely vesicles, into distinct membrane domains on the extracellular surface of the plasma membrane. Surface ASM initia...