Aguilar-Dorado Itzel-Citlalli, Hernández Gerardo, Quintanar-Escorza Martha-Angelica, Maldonado-Vega María, Rosas-Flores Margarita, Calderón-Salinas José-Víctor
Biochemistry Department, Centro de Investigación y Estudios Avanzados IPN, México, DF, Mexico.
Section of Methodology of Science, Centro de Investigación y Estudios Avanzados IPN, México, DF, Mexico.
Toxicol Appl Pharmacol. 2014 Dec 1;281(2):195-202. doi: 10.1016/j.taap.2014.10.003. Epub 2014 Oct 27.
Eryptosis is a physiological phenomenon in which old and damaged erythrocytes are removed from circulation. Erythrocytes incubated with lead have exhibited major eryptosis. In the present work we found evidence of high levels of eryptosis in lead exposed workers possibly via oxidation. Blood samples were taken from 40 male workers exposed to lead (mean blood lead concentration 64.8μg/dl) and non-exposed workers (4.2μg/dl). The exposure to lead produced an intoxication characterized by 88.3% less δ-aminolevulinic acid dehydratase (δALAD) activity in lead exposed workers with respect to non-lead exposed workers. An increment of oxidation in lead exposed workers was characterized by 2.4 times higher thiobarbituric acid-reactive substance (TBARS) concentration and 32.8% lower reduced/oxidized glutathione (GSH/GSSG) ratio. Oxidative stress in erythrocytes of lead exposed workers is expressed in 192% higher free calcium concentration [Ca(2+)]i and 1.6 times higher μ-calpain activity with respect to non-lead exposed workers. The adenosine triphosphate (ATP) concentration was not significantly different between the two worker groups. No externalization of phosphatidylserine (PS) was found in non-lead exposed workers (<0.1%), but lead exposed workers showed 2.82% externalization. Lead intoxication induces eryptosis possibly through a molecular pathway that includes oxidation, depletion of reduced glutathione (GSH), increment of [Ca(2+)], μ-calpain activation and externalization of PS in erythrocytes. Identifying molecular signals that induce eryptosis in lead intoxication is necessary to understand its physiopathology and chronic complications.
红细胞凋亡是一种生理现象,即衰老和受损的红细胞从循环中被清除。与铅一起孵育的红细胞表现出主要的红细胞凋亡。在本研究中,我们发现铅暴露工人中可能通过氧化存在高水平红细胞凋亡的证据。从40名铅暴露男性工人(平均血铅浓度64.8μg/dl)和非暴露工人(4.2μg/dl)采集血样。铅暴露导致中毒,其特征是铅暴露工人的δ-氨基乙酰丙酸脱水酶(δALAD)活性相对于非铅暴露工人降低了88.3%。铅暴露工人氧化增加的特征是硫代巴比妥酸反应性物质(TBARS)浓度高2.4倍,还原型/氧化型谷胱甘肽(GSH/GSSG)比值低32.8%。铅暴露工人红细胞中的氧化应激表现为游离钙浓度[Ca(2+)]i比非铅暴露工人高192%,μ-钙蛋白酶活性高1.6倍。两组工人的三磷酸腺苷(ATP)浓度没有显著差异。在非铅暴露工人中未发现磷脂酰丝氨酸(PS)外化(<0.1%),但铅暴露工人显示出2.82%的外化。铅中毒可能通过包括氧化、还原型谷胱甘肽(GSH)耗竭、[Ca(2+)]增加、μ-钙蛋白酶激活和红细胞中PS外化的分子途径诱导红细胞凋亡。识别铅中毒中诱导红细胞凋亡的分子信号对于理解其生理病理学和慢性并发症是必要的。