Smit M J, Anderson R
Department of Immunology, Faculty of Medicine, University of Pretoria, Republic of South Africa.
Agents Actions. 1992 May;36(1-2):58-65. doi: 10.1007/BF01991229.
Both H2O2 (IC50 = 70 microM) and HOCl (IC50 = 8.5 microM) inhibited mitogen-induced MNL proliferation in a dose-dependent manner. This was found to be due to a depletion of intracellular ATP by at least two distinct mechanisms. HOCl and high concentrations (greater than 100 microM) of H2O2 inhibit ATP generation via sulfhydryl group oxidation on the active site of the glyceraldehyde-3-phosphate dehydrogenase (G3PDH) enzyme of the glycolytic pathway. On the other hand, low H2O2 concentrations cause ATP depletion by an activation of the DNA repair enzyme, poly(ADP-ribose)polymerase (pADPRP), leading to consumption of NAD+, an essential cofactor for G3PDH. The anti-oxidants ascorbate and cysteine protected MNL against the anti-proliferative effects of HOCl. Similar results were achieved with the HOCl-mediated inhibition of ATP production and G3PDH activity. However, ascorbate was unable to protect against H2O2-mediated inhibition of MNL functions, while cysteine protected against the inhibitory effects on ATP production and G3PDH activity, induced by this oxidant.
H2O2（IC50 = 70微摩尔）和HOCl（IC50 = 8.5微摩尔）均以剂量依赖的方式抑制有丝分裂原诱导的人外周血单个核细胞（MNL）增殖。发现这是由于通过至少两种不同机制导致细胞内ATP耗竭所致。HOCl和高浓度（大于100微摩尔）的H2O2通过糖酵解途径中甘油醛-3-磷酸脱氢酶（G3PDH）酶活性位点上的巯基氧化来抑制ATP生成。另一方面，低浓度的H2O2通过激活DNA修复酶聚（ADP-核糖）聚合酶（pADPRP）导致ATP耗竭，从而导致NAD +消耗，NAD +是G3PDH的必需辅因子。抗氧化剂抗坏血酸和半胱氨酸可保护MNL免受HOCl的抗增殖作用。HOCl介导的ATP产生抑制和G3PDH活性也得到了类似结果。然而，抗坏血酸无法保护MNL免受H2O2介导的功能抑制，而半胱氨酸可保护其免受该氧化剂诱导的对ATP产生和G3PDH活性的抑制作用。
