Metabolomic and proteomic biomarkers for III-V semiconductors: chemical-specific porphyrinurias and proteinurias.
Metabolomic and proteomic biomarkers for III-V semiconductors: chemical-specific porphyrinurias and proteinurias.
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III-V 族半导体的代谢组学和蛋白质组学生物标志物：化学特异性卟啉尿和蛋白尿。
DOI：
10.1016/j.taap.2005.01.020
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发表时间：
2005
影响因子：
3.8
通讯作者：
Yamauchi,Hiroshi
中科院分区：
文献类型：
--
作者：
Fowler,BruceA;Conner,ElizabethA;Yamauchi,Hiroshi
迫切需要开发和验证分子生物标志物，以评估单独和混合的化学制剂的早期影响。对于新的化学密集型工业，如半导体工业，尤其如此。该实验室和其他实验室的先前研究已经证明了III-V族半导体砷化镓（GaAs）和砷化铟（InAs）的血红素生物合成途径的元素特异性改变，伴随着特定血红素前体的尿排泄增加。这些数据代表了代谢组学生物标志物的一个例子，在临床疾病发展之前早期评估化学作用。先前的研究已经证明，向仓鼠体内或皮下施用GaAs和InAs颗粒可诱导肾近曲小管细胞中的主要应激蛋白基因家族。这是监测35-S蛋氨酸标记的基因产物，然后通过二维凝胶电泳后暴露于InAs颗粒。目前的研究检查这些影响是否与化合物特异性蛋白尿的发展后10天或30天后皮下注射GaAs或InAs颗粒在仓鼠。这些研究的结果表明，在10和30天不同的肾小管细胞蛋白质表达模式的GaAs和InAs特异性改变的发展。在30天的时间点，接受InAs颗粒的仓鼠中的细胞显示出蛋白质表达的显著衰减，表明应激蛋白反应的抑制。这些变化与GaAs和InAs蛋白尿模式，通过二维凝胶电泳和银染色监测。蛋白质排泄模式的强度在10天和30天之间增加，并且在30天InAs治疗组的动物中最为明显。在这些动物的肾小管细胞中未观察到明显的细胞死亡形态学体征。用32-、70-和90-kDa应激蛋白家族的抗体对尿液进行Western印迹分析，未显示这些分子的存在，表明这些蛋白质未在尿液样品中排泄。这些数据表明，所观察到的蛋白尿模式不是细胞死亡的结果，并且所观察到的化学特异性蛋白尿在显著的细胞毒性之前产生。这些研究结果表明一个假设，涉及GaAs和InAs干扰应激蛋白陪伴重吸收蛋白质的蛋白质体降解和可能的陪伴受损的细胞内蛋白质从肾近曲小管细胞进入尿滤液。总体而言，这些研究的结果提供了关于这些半导体化合物肾毒性的进一步信息。他们还建议使用二维凝胶电泳结合尿蛋白模式的银染色作为与肾小管细胞中细胞内蛋白毒性相关的早期肾损伤的潜在有用的蛋白质组学方法。
A pressing need exists to develop and validate molecular biomarkers to assess the early effects of chemical agents, both individually and in mixtures. This is particularly true for new and chemically intensive industries such as the semiconductor industry. Previous studies from this laboratory and others have demonstrated element-specific alterations of the heme biosynthetic pathway for the III–V semiconductors gallium arsenide (GaAs) and indium arsenide (InAs) with attendant increased urinary excretion of specific heme precursors. These data represent an example of a metabolomic biomarker to assess chemical effects early, before clinical disease develops. Previous studies have demonstrated that the intratracheal or subcutaneous administration of GaAs and InAs particles to hamsters produces the induction of the major stress protein gene families in renal proximal tubule cells. This was monitored by 35-S methionine labeling of gene products followed by two-dimensional gel electrophoresis after exposure to InAs particles. The present studies examined whether these effects were associated with the development of compound-specific proteinuria after 10 or 30 days following subcutaneous injection of GaAs or InAs particles in hamsters. The results of these studies demonstrated the development of GaAs- and InAs-specific alterations in renal tubule cell protein expression patterns that varied at 10 and 30 days. At the 30-day point, cells in hamsters that received InAs particles showed marked attenuation of protein expression, suggesting inhibition of the stress protein response. These changes were associated with GaAs and InAs proteinuria patterns as monitored by two-dimensional gel electrophoresis and silver staining. The intensity of the protein excretion patterns increased between the 10- and 30-day points and was most pronounced for animals in the 30-day InAs treatment group. No overt morphologic signs of cell death were seen in renal tubule cells of these animals. Western blot analyses of the urines with antibodies to the 32-, 70-, and 90-kDa stress protein families did not show the presence of these molecules, indicating that these proteins were not excreted in the urine samples. These data suggest that the observed proteinuria patterns were not a result of cell death and that the observed chemical-specific proteinurias were produced before marked cellular toxicity. These findings suggest a hypothesis involving GaAs and InAs interference with stress protein chaperoning of reabsorbed proteins for proteosomic degradation and the probable chaperoning of damaged intracellular proteins from renal proximal tubule cells into the urinary filtrate. Overall, the results of these studies provide further information on the nephrotoxicity of these semiconductor compounds. They also suggest the use of two-dimensional gel electrophoresis with silver staining of urinary protein patterns as a potentially useful proteomic approach to renal damage early in relation to intracellular proteotoxicity in kidney tubule cells.
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影响因子：
3.8
作者：
Yamauchi,H;Takahashi,K;Yamamura,Y;Fowler,BA
通讯作者：
Fowler,BA
长期接触砷酸钠期间，哺乳动物肝血红素生物合成和尿卟啉排泄的调节发生改变。
影响因子：
3.8
作者：
J. S. Woods;B. Fowler
通讯作者：
B. Fowler
通过亚砷酸钠、重金属和硫醇反应剂诱导 32-和 34-kDa 应激蛋白。
影响因子：
4.8
作者：
M. Caltabiano;T. Koestler;G. Poste;R. Greig
通讯作者：
R. Greig
影响因子：
56.9
作者：
BECKMANN, RP;MIZZEN, LA;WELCH, WJ
通讯作者：
WELCH, WJ
氯化铟改变肝脏血红素代谢的调节。
影响因子：
3.8
作者：
J. S. Woods;G. Carver;B. Fowler
通讯作者：
B. Fowler