Biomaterial Database

Protein kinase C-independent selective induction of nitric oxide synthase activity in rat alveolar macrophages by staurosporine. 1998

R Tabakman, and P Lazarovici, and Y Matsuda, and C Brodie, and H Ovadia

Department of Pharmacology, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Israel.

The purpose of this study was to characterize the effect of the K-252a family of protein kinase inhibitors with emphasis on staurosporine (ST), on stimulation of the inducible nitric oxide synthase activity in rat alveolar NR8383 macrophages. We found that ST, but not K-252a, K-252b, KT-5720, and KT-5823, selectively enhanced the basal or the lipopolysaccharide (LPS)-induced nitric oxide production. ST-induced NO production was blocked by L-NAME, K-252a, and phosphatase inhibitors and could not be mimicked by other protein kinase C (PKC) inhibitors such as calphostine. An additive effect between ST and PMA on NO production was observed. LPS and PMA but not ST induced PKCbeta translocation from the cytosol to the membrane fraction. ST may induce and affect the state of phosphorylation of iNOS via PKC-independent mechanisms. ST provides an important pharmacological tool to investigate PKC-independent signal transduction pathways which regulate iNOS, induction, and activity in rat NR8383 macrophages.

UI	MeSH Term	Description	Entries
D007527	Isoenzymes	Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.	Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D008070	Lipopolysaccharides	Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)	Lipopolysaccharide,Lipoglycans
D009573	Nitrites	Salts of nitrous acid or compounds containing the group NO2-. The inorganic nitrites of the type MNO2 (where M	Nitrite
D010744	Phosphoric Monoester Hydrolases	A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate.	Phosphatase,Phosphatases,Phosphohydrolase,Phosphohydrolases,Phosphomonoesterase,Phosphomonoesterases,Phosphoric Monoester Hydrolase,Hydrolase, Phosphoric Monoester,Hydrolases, Phosphoric Monoester,Monoester Hydrolase, Phosphoric
D010766	Phosphorylation	The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.	Phosphorylations
D011493	Protein Kinase C	An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.	Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D002227	Carbazoles	Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D004790	Enzyme Induction	An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.	Induction, Enzyme
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme