Staurosporine analogs promote distinct patterns of process outgrowth and polyploidy in small cell lung carcinoma cells.

We have recently shown that staurosporine mediates the conversion of small cell lung carcinoma (SCLC) cells into a neuron-like process-bearing phenotype. Here, we have extended these studies to the staurosporine analogs K252a, lestaurtinib, PKC412, stauprimide, and UCN-01 and analyzed their influence on process extension, cell cycle distribution, and induction of polyploidy in four SCLC cell lines. In GLC-2 cells, all compounds provoked extensive process formation with the exception of PKC412 that showed no response.

Regulation of the NPC2 protein-mediated cholesterol trafficking by membrane lipids.

Recycling and turnover of cell membranes play a critical role in cell metabolism. The internalization of membranes through the different processes of endocytosis, phagocytosis, and autophagy deliver a considerable amount of membranes and lipids to the endosomal and lysosomal system which is tasked with its degradation. Its failure to do so leads to severe fatal neurodegenerative diseases.

Biological function of the cellular lipid BMP-BMP as a key activator for cholesterol sorting and membrane digestion.

Bis(monoacylglycero)phosphate (BMP) is one of the most intriguing classes of lipids discovered to date. Its biosynthetic pathway is still not fully known, even though studies point to cardiolipin and PG as sources. BMP has an unusual stereoconfiguration which is responsible for its slow catabolism.

Optimization of submerged keratinocyte cultures for the synthesis of barrier ceramides.

Epidermal differentiation results in the formation of the extracellular lipid barrier in the stratum corneum, which mainly consists of ceramides, free fatty acids, and cholesterol. Differentiating keratinocytes of the stratum granulosum synthesize a series of complex long-chain ceramides and glucosylceramides with different chain lengths and hydroxylation patterns at intracellular membranes of the secretory pathway. Formation of complex extracellular ceramides parallels the transition of keratinocytes from the stratum granulosum to the stratum corneum, where their precursors, complex glucosylceramides and sphingomyelin, are secreted and exposed to extracellular lysosomal lipid hydrolases.

Integrity and barrier function of the epidermis critically depend on glucosylceramide synthesis.

Ceramides are vital components of the water barrier in mammalian skin. Epidermis-specific, a major ceramide portion contains omega-hydroxy very long chain fatty acids (C30-C36). These omega-hydroxy ceramides (Cers) are found in the extracellular lamellae of the stratum corneum either as linoleic acyl esters or protein bound.

Nitric oxide regulates synthesis of gene products involved in keratinocyte differentiation and ceramide metabolism.

During terminal differentiation of keratinocytes the expression of various proteins, which are required for the formation of the epidermal water barrier in the skin of land dwelling animals, is upregulated. Using a cell culture model for the differentiation of human keratinocytes and real-time PCR, we quantified the mRNA levels of several proteins involved in differentiation and ceramide metabolism. A calcium shift (1.