Valacchi Giuseppe, Vasu Vihas T, Yokohama Wallace, Corbacho Ana M, Phung Anh, Lim Yunsook, Aung Hnin Hnin, Cross Carroll E, Davis Paul A
Center for Comparative Respiratory Biology and Medicine, Department of Internal Medicine, University of California Davis, Davis, CA 95616, USA.
Toxicol Appl Pharmacol. 2007 Jul 15;222(2):227-34. doi: 10.1016/j.taap.2007.04.010. Epub 2007 May 1.
Despite the physiological importance of alpha-tocopherol (AT), the molecular mechanisms involved in maintaining cellular and tissue tocopherol levels remain to be fully characterized. Scavenger receptor B1 (SRB1), one of a large family of scavenger receptors, has been shown to facilitate AT transfer from HDL to peripheral tissues via apo A-1-mediated processes and to be important in the delivery of AT to the lung cells. In the present studies the effects of age and two environmental oxidants ozone (O(3)) (0.25 ppm 6 h/day) and cigarette smoke (CS) (60 mg/m(3) 6 h/day) for 4 days on selected aspects of AT transport in murine lung tissues were assessed. While AT levels were 25% higher (p<0.05) and 15% lower (p<0.05) in plasma and lung tissue, respectively, in aged versus young mice, acute environmental exposure to O(3) or CS at the doses used had no effect. Gene expression levels, determined by RT-PCR of AT transport protein (ATTP), SRB1, CD36, ATP binding cassette 3 (ABCA3) and ABCA1 and protein levels, determined by Western blots for SRB1, ATTP and ABCA1 were assessed. Aged mouse lung showed a lower levels of ATTP, ABCA3 and SRB1 and a higher level CD36 and ABCA1. Acute exposure to either O(3) or CS induced declines in ATTP and SRB1 in both aged and young mice lung. CD36 increased in both young and aged mice lung upon exposure to O(3) and CS. These findings suggest that both age and environmental oxidant exposure affect pathways related to lung AT homeostasis and do so in a way that favors declines in lung AT. However, given the approach taken, the effects cannot be traced to changes in these pathways or AT content in any specific lung associated cell type and thus highlight the need for further follow-up studies looking at specific lung associated cell types.
尽管α-生育酚(AT)具有重要的生理意义,但维持细胞和组织中生育酚水平的分子机制仍有待全面阐明。清道夫受体B1(SRB1)是清道夫受体大家族中的一员,已被证明可通过载脂蛋白A-1介导的过程促进AT从高密度脂蛋白(HDL)转移至外周组织,并且在将AT递送至肺细胞的过程中发挥重要作用。在本研究中,评估了年龄以及两种环境氧化剂臭氧(O₃)(0.25 ppm,每天6小时)和香烟烟雾(CS)(60 mg/m³,每天6小时)连续4天对小鼠肺组织中AT转运某些方面的影响。与年轻小鼠相比,老年小鼠血浆和肺组织中的AT水平分别高出25%(p<0.05)和低15%(p<0.05),但以所用剂量对O₃或CS进行急性环境暴露并无影响。通过逆转录-聚合酶链反应(RT-PCR)测定了AT转运蛋白(ATTP)、SRB1、CD36、ATP结合盒转运体3(ABCA3)和ABCA1的基因表达水平,并通过蛋白质印迹法测定了SRB1、ATTP和ABCA1的蛋白质水平。老年小鼠肺组织中ATTP、ABCA3和SRB1水平较低,而CD36和ABCA1水平较高。对老年和年轻小鼠肺组织进行O₃或CS急性暴露均导致ATTP和SRB1水平下降。暴露于O₃和CS后,年轻和老年小鼠肺组织中的CD36均增加。这些发现表明,年龄和环境氧化剂暴露均会影响与肺AT稳态相关的途径,且均以有利于肺AT水平下降的方式发挥作用。然而,鉴于所采用的方法,这些影响无法追溯至这些途径或任何特定肺相关细胞类型中AT含量的变化,因此突出了进一步开展针对特定肺相关细胞类型的后续研究的必要性。