Requirement of nitric oxide and calcium mobilization for the induction of apoptosis in adrenal vascular endothelial cells

FEBS Letters

Boscá, Lisardo²  López-Collazo, Eduardo²  Mateo, Jesús¹  Miras-Portugal, Marı́a T¹ 

[1] Departamento de Bioquı́mica y Biologı́a Molecular IV, Facultad de Veterinaria, Universidad Complutense, 28040 Madrid, Spain;Instituto de Bioquı́mica (CSIC-UCM), Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain

关键词: Apoptosis;    Endothelial cell;    Nitric oxide;    Calcium agonist;    AVEC;    vascular endothelial cell(s);    LPS;    lipopolysaccharide;    NOS2;    cytokine-inducible Ca2+-inducible nitric oxide synthase;    TNF-α;    tumour necrosis factor-α;    SIN-1;    3-morpholinosydnonimine;    SIN-10;    molsidomine;    GSNO;    S-nitrosoglutathion;    SNAP;    S-nitroso-N-acetyl-penicillamine;   

DOI  :  10.1016/S0014-5793(97)00893-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Exposure of adrenal vascular endothelial cells (AVEC) to pharmacological nitric oxide (NO) donors, pro-inflammatory 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-1β (IL-1β) 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.

【 授权许可】

Unknown