Crespo M E, Bicho M P
Laboratory of Endocrinology, Portuguese Cancer Institute Francisco Gentil, Lisboa, Portugal.
Biol Signals. 1995 Mar-Apr;4(2):78-85. doi: 10.1159/000109425.
The effects of epinephrine and two other beta 2-adrenergic agonists, ritodrine and isoxsuprine, on the induction of damage to the DNA (production of strand breaks) in human leukocytes were studied by fluorescence analyses of unwinding DNA. Epinephrine stimulated the development of DNA strand breaks. Ritodrine and isoxsuprine inhibited this effect of epinephrine on the human leukocytes by competition for binding to receptors, but they were not oxidized to the same extent as epinephrine. Metoprolol, which acts predominantly as a beta 1-antagonist, demonstrated a beta 2-antagonism, as compared with epinephrine. Since the o-oxidation of epinephrine involves the production of damaging oxygen species such as O2-. and H2O2, we studied the effects on DNA of extracellular H2O2 in the presence and absence of epinephrine. Extracellular H2O2 induced significant damage to the DNA, but it had a smaller effect when applied with epinephrine. The results obtained with 3-amino-1,2,4-triazole, an inhibitor of endogenous catalase, were not significantly different from control results, under our experimental conditions. Nevertheless, this compound had a mitigating effect when applied with epinephrine. We also investigated the action of nicotinamide in the presence and absence of epinephrine. The results demonstrated the importance of nicotinamide in cellular oxidative stress. Two antioxidant enzymes, superoxide dismutase and catalase, inhibited the epinephrine-induced damage to DNA.
通过对解旋DNA的荧光分析，研究了肾上腺素以及另外两种β2 - 肾上腺素能激动剂利托君和异克舒令对人白细胞DNA损伤诱导（链断裂产生）的影响。肾上腺素刺激了DNA链断裂的发展。利托君和异克舒令通过竞争受体结合来抑制肾上腺素对人白细胞的这种作用，但它们的氧化程度不如肾上腺素。与肾上腺素相比，主要作为β1 - 拮抗剂起作用的美托洛尔表现出β2 - 拮抗作用。由于肾上腺素的邻位氧化涉及产生如超氧阴离子和过氧化氢等具有损伤性的氧物种，我们研究了在有和没有肾上腺素存在的情况下细胞外过氧化氢对DNA的影响。细胞外过氧化氢诱导了显著的DNA损伤，但与肾上腺素一起应用时其作用较小。在我们的实验条件下，内源性过氧化氢酶抑制剂3 - 氨基 - 1,2,4 - 三唑得到的结果与对照结果没有显著差异。然而，该化合物与肾上腺素一起应用时具有减轻作用。我们还研究了在有和没有肾上腺素存在的情况下烟酰胺的作用。结果证明了烟酰胺在细胞氧化应激中的重要性。两种抗氧化酶，超氧化物歧化酶和过氧化氢酶，抑制了肾上腺素诱导的DNA损伤。
