Robison T W, Zhou H, Kim K J
Department of Molecular Pharmacology, Will Rogers Institute Pulmonary Research Center; University of Southern California, Los Angeles 90033, USA.
Environ Health Perspect. 1996 Aug;104(8):852-6. doi: 10.1289/ehp.96104852.
Pulmonary injury from nitrogen dioxide (NO2) may in part be related to the generation of aldehydic compounds, which bind with cellular proteins and subsequently impair or inhibit cell function. We examined the generation of aldehydes from guinea pig tracheobronchial epithelial (GPTE) cell monolayers exposed to NO2. With the use of dinitrophenylhydrazine (DNP) to derivatize aldehydic compounds, glycolaldehyde, a two carbon alpha-hydroxyaldehyde, was identified in elevated levels in the basolateral fluid from monolayers exposed to NO2. DNP-glycolaldehyde levels were 81.2 +/- 2.7 and 234.0 +/- 42.6 nM in response to a 1-hr exposure to 1 and 5 ppm NO2, respectively, as compared to an air-control value of 20.3 +/- 6.8 nM. Taking into account dilution and reactivity, cellular glycolaldehyde levels could have reached as high as 3 mM for the 60-min exposure period (i.e., 0.05 mM/min). The effects of exogenous glycolaldehyde on GPTE ouabain-sensitive basolateral 86Rb uptake (an index of Na+,K(+)-ATPase activity) were examined and compared with the actions of NO2 exposure. Bolus addition of glycolaldehyde to the basolateral fluid at concentrations > or = 5 mM led to an inhibition of ouabain-sensitive 86Rb uptake, while lower concentrations had no effect. the effects of exogenous glycolaldehyde differ from NO2 exposure, which led to a sustained elevation of ouabain-sensitive 86Rb uptake with presumed generation of glycolaldehyde at a continuous low level. Glycolaldehyde does not appear to play a significant role in the acute alterations of sodium pump activity, suggesting that the NO2-induced changes in Na+,K(+)-ATPase activity of GPTE monolayers probably are further mediated by other lipid peroxidation products/oxidation processes yet to be identified.
二氧化氮（NO₂）造成的肺损伤可能部分与醛类化合物的生成有关，醛类化合物会与细胞蛋白结合，进而损害或抑制细胞功能。我们研究了暴露于NO₂的豚鼠气管支气管上皮（GPTE）细胞单层中醛类的生成情况。使用二硝基苯肼（DNP）对醛类化合物进行衍生化处理后，在暴露于NO₂的细胞单层基底外侧液中，二碳α-羟基醛乙醇醛的水平显著升高。与空气对照值20.3±6.8 nM相比，暴露于1 ppm和5 ppm NO₂ 1小时后，DNP-乙醇醛水平分别为81.2±2.7 nM和234.0±42.6 nM。考虑到稀释和反应活性，在60分钟的暴露期内，细胞内乙醇醛水平可能高达3 mM（即0.05 mM/分钟）。研究了外源性乙醇醛对GPTE哇巴因敏感的基底外侧⁸⁶Rb摄取（Na⁺，K⁺-ATP酶活性指标）的影响，并与NO₂暴露的作用进行了比较。向基底外侧液中一次性加入浓度≥5 mM的乙醇醛会导致哇巴因敏感的⁸⁶Rb摄取受到抑制，而较低浓度则无此作用。外源性乙醇醛的作用与NO₂暴露不同，NO₂暴露会导致哇巴因敏感的⁸⁶Rb摄取持续升高，推测是由于持续产生低水平的乙醇醛。乙醇醛似乎在钠泵活性的急性改变中不起重要作用，这表明NO₂诱导的GPTE细胞单层Na⁺，K⁺-ATP酶活性变化可能进一步由其他尚未确定的脂质过氧化产物/氧化过程介导。
