Requirement of nitric oxide and calcium mobilization for the induction of apoptosis in adrenal vascular endothelial cells.
Exposure of adrenal vascular endothelial cells (AVEC) to pharmacological nitric oxide (NO) donors, proinflammatory cytokines or lipopolysaccharide was unable to induce apoptosis as occurred when macrophages were treated under identical experimental conditions. However, when the intracellular Ca2+ concentration increased, AVEC displayed apoptotic features upon exposure to NO. This apoptosis was confirmed by the release of oligonucleosomes to the cytosol and by the characteristic DNA laddering observed after electrophoresis in agarose gels. Ca2+-mobilizing agents and interleukin-1beta (IL-1beta) also elicited an apoptotic response in these cells through a mechanism that required NO synthesis. The ability of NO and intracellular Ca2+ to promote apoptosis was dependent on the number of passages of the cells in culture, suggesting the loss of protective factors in the course of ex vivo cell culture. Because AVEC exhibit an important capacity to increase the intracellular Ca2+ concentration in response to a wide array of agonists, this condition might affect the integrity of the vascular system under pathological circumstances such as those prevailing in the course of septic shock.
López-Collazo
E
E
Instituto de Bioquímica (CSIC-UCM), Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
Mateo
J
J
Miras-Portugal
M T
MT
Boscá
L
L
D000311:Adrenal Glands; D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000008:administration & dosage / Q000494:pharmacology*; D002417:Cattle; D016207:Cytokines / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002118:Calcium