Biomaterial Database

Calcium-dependent second-messenger regulation of low-density lipoprotein oxidation by human aortic smooth muscle cells. 1996

K E Wells, and J J Alexander, and R Miguel

Case Western Reserve University, MetroHealth Medical Center, Cleveland, Ohio 44109, USA.

BACKGROUND We postulated that the response of vascular smooth muscle cells (SMCs) to oxidized low-density lipoprotein (LDL) may be modulated through calcium and 3', 5' cyclic adenosine monophosphate (Ca+2-cAMP) second-messenger activity. METHODS Changes in cytosolic calcium [Ca+2]i in aortic SMCs exposed to native (N-) and oxidized (Ox-) LDL were measured with a Fura 2-AM indicator. The influence of cAMP on this response was determined by incubating the cells with either forskolin or 8-bromo-cAMP (stimulatory) or galanin (inhibitory). The cells were then activated by an initial preincubation with N- or Ox-LDL, and the subsequent cellular oxidation of N-LDL was measured. The effect of cAMP mediators alone or in conjunction with calcium antagonism was studied. RESULTS Exposure of SMCs to Ox-LDL resulted in a marked elevation of [Ca+2]i(306 +/- 12 nmol/L) compared with that in the control group (192 +/- 15 nmol/Liter; p < 10(-6)). This response was augmented by cAMP stimulation (406 +/- 8 nmol/L; p < 10(-6)) but reduced by cAMP inhibition (247 +/- 8 nmol/L; p < 10(-6)). The activation of intracellular signaling by initial Ox-LDL priming increased the subsequent oxidation of N-LDL (0.40 +/- 0.02 nmol malondialdehyde versus 0.24 +/- 0.02 nmol MDA control; p < 10(-4)). This response was enhanced by cAMP (0.45 +/- 0.03 nmol MDA; p < 10(-4)) and inhibited by galanin (0.26 +/- 0.02; p < 10(-4)). The cAMP effect was reversed by the blockade of calcium mobilization via membrane channels and reticular release. CONCLUSIONS Oxidized LDL-induced Ca+2-cAMP signaling modulates the cellular oxidation of N-LDL. This finding suggests a mechanism through which the scavenger uptake of modified LDL may potentially be regulated.

UI	MeSH Term	Description	Entries
D008077	Lipoproteins, LDL	A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues.	Low-Density Lipoprotein,Low-Density Lipoproteins,beta-Lipoprotein,beta-Lipoproteins,LDL(1),LDL(2),LDL-1,LDL-2,LDL1,LDL2,Low-Density Lipoprotein 1,Low-Density Lipoprotein 2,LDL Lipoproteins,Lipoprotein, Low-Density,Lipoproteins, Low-Density,Low Density Lipoprotein,Low Density Lipoprotein 1,Low Density Lipoprotein 2,Low Density Lipoproteins,beta Lipoprotein,beta Lipoproteins
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
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
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
D003300	Copper	A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.	Copper-63,Copper 63
D003600	Cytosol	Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.	Cytosols
D005576	Colforsin	Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.	Coleonol,Forskolin,N,N-Dimethyl-beta-alanine-5-(acetyloxy)-3-ethenyldodecahydro-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-1H-naphtho(2,1-b)pyran-6-yl Ester HCl,NKH 477,NKH-477,NKH477
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000242	Cyclic AMP	An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.	Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic