Biomaterial Database

Nitric oxide causes apoptosis in pulmonary vascular smooth muscle cells. 1998

J D Smith, and S D McLean, and D K Nakayama

Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7210, USA.

Nitric oxide (NO), a product of certain cytokine-activated cells, affects rates of apoptosis, a mechanism of programmed cell death. We asked whether NO affected rates of apoptosis in pulmonary vascular cells. Using rat pulmonary artery smooth muscle cells, we studied direct effects of the NO donor SG-nitroso-acetyl-D,L-penicillamine (SNAP) and the effects of NO endogenously synthesized in response to bacterial lipopolysaccharide (LPS) and inflammatory cytokines interleukin-1beta, interferon-gamma, and tumor necrosis factor-alpha (a combination called cytomix for convenience). We determined apoptosis on the basis of light microscopy and the bromodeoxyuridine terminal deoxynucleotidyl transferase reaction (BrdUTdT). Both SNAP- and cytomix-induced synthesis of NO resulted in histologic evidence of apoptosis based upon fluorescence microscopy using propidium iodide. SNAP (10(-5) M) increased BrdUTdT-positive cells from 17.5 to 78.4% compared with basal medium alone, with the maximal response occurring at 15 h or exposure. Exposing cells to LPS and cytokines induced NO production (from 0.1 +/- 0.1 to 24.6 +/- 0.5 microM, P < 0.05) caused cytological changes consistent with apoptosis and led to an increase of increased BrdUTdT-positive cells from 11 to 41% at 12 h compared with basal medium alone. The competitive NO synthase inhibitor NG-monomethyl-L-arginine inhibited both NO synthesis and NO apoptosis, returning the proportion of BrdUTdT-positive cells (6%) to levels below control. L-Arginine (0.5 mM) restored percentages to those increase in response to endogenously synthesized NO, and NO is a potential mechanism of acute lung injury in response to inflammatory cytokines.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009131	Muscle, Smooth, Vascular	The nonstriated involuntary muscle tissue of blood vessels.	Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D009569	Nitric Oxide	A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.	Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D010396	Penicillamine	3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease.	Dimethylcysteine,Mercaptovaline,beta,beta-Dimethylcysteine,Copper Penicillaminate,Cuprenil,Cuprimine,D-3-Mercaptovaline,D-Penicillamine,Metalcaptase,D 3 Mercaptovaline,D Penicillamine,Penicillaminate, Copper,beta,beta Dimethylcysteine
D011651	Pulmonary Artery	The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs.	Arteries, Pulmonary,Artery, Pulmonary,Pulmonary Arteries
D001973	Bromodeoxyuridine	A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors.	BUdR,BrdU,Bromouracil Deoxyriboside,Broxuridine,5-Bromo-2'-deoxyuridine,5-Bromodeoxyuridine,NSC-38297,5 Bromo 2' deoxyuridine,5 Bromodeoxyuridine,Deoxyriboside, Bromouracil
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004253	DNA Nucleotidylexotransferase	A non-template-directed DNA polymerase normally found in vertebrate thymus and bone marrow. It catalyzes the elongation of oligo- or polydeoxynucleotide chains and is widely used as a tool in the differential diagnosis of acute leukemias in man. EC 2.7.7.31.	Terminal Addition Enzyme,Terminal Deoxyribonucleotidyltransferase,Deoxynucleotidyl Transferase,Deoxynucleotidyltransferase,Desoxynucleotidyl Transferase,Desoxynucleotidyltransferase,Tdt Antigen,Terminal Deoxynucleotidyl Transferase,Terminal Deoxyribonucleotidyl Transferase,Addition Enzyme, Terminal,Antigen, Tdt,Deoxynucleotidyl Transferase, Terminal,Deoxyribonucleotidyl Transferase, Terminal,Deoxyribonucleotidyltransferase, Terminal,Enzyme, Terminal Addition,Nucleotidylexotransferase, DNA,Transferase, Deoxynucleotidyl,Transferase, Desoxynucleotidyl,Transferase, Terminal Deoxynucleotidyl,Transferase, Terminal Deoxyribonucleotidyl
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
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia