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人肾皮质和肿瘤组织中的谷胱甘肽S-转移酶:酶活性、同工酶谱及免疫组织化学定位

Glutathione S-transferases in human renal cortex and neoplastic tissue: enzymatic activity, isoenzyme profile and immunohistochemical localization.

作者信息

Rodilla V, Benzie A A, Veitch J M, Murray G I, Rowe J D, Hawksworth G M

机构信息

Department of Medicine, University of Aberdeen, Foresterhill, UK.

出版信息

Xenobiotica. 1998 May;28(5):443-56. doi: 10.1080/004982598239371.

DOI:10.1080/004982598239371
PMID:9622847
Abstract
  1. Glutathione S-transferase (GST) activity in the cytosol of renal cortex and tumours from eight men and eight women was measured using 1-chloro-2,4-dinitrobenzene (CDNB) as a substrate. GST activities ranged from 685 to 2192 nmol/min/mg protein in cortex (median 1213) and from non-detectable (minimum 45) to 2424 nmol/min/mg protein in tumours (median 469). The activities in the tumours were lower than those in the normal cortices (p < 0.05). 2. In men, the activity in the cortical cytosol was in all cases higher than that measured in the corresponding tumours (p < 0.05). In women, the difference in activity between cortices and tumours was not significantly different (p > 0.05). 3. The age of the patients ranged from 42 to 81 years (median 62) and was not found to play a role in the levels of GST activity observed in cortex or in renal tumours from either sex. 4. Immunoblotting and immunohistochemical studies confirmed that GST-alpha was the predominant form expressed both in normal cortex and tumour and probably accounted for most of the GST activity present in these samples. GST-mu and GST-phi were expressed in both tumours and normal cortex and, while in some cases the level of expression in the cortices was higher than that found in the tumours, the reverse was also observed. Within the GST-mu class, GST M1/M2 was only detected in one sample (tumour), which showed the highest overall expression of GST-mu. GSTM3 was the predominant isoenzyme of the mu class in normal and tumour tissue, whereas GTM4 and GSTM5 were not detected. 5. These differences could have functional significance where xenobiotics or cytotoxic drugs are specific substrates for the different classes of GSTs.
摘要
  1. 以1-氯-2,4-二硝基苯(CDNB)为底物,测定了8名男性和8名女性肾皮质和肿瘤细胞溶质中的谷胱甘肽S-转移酶(GST)活性。肾皮质中GST活性范围为685至2192 nmol/分钟/毫克蛋白质(中位数为1213),肿瘤中为不可检测(最小值45)至2424 nmol/分钟/毫克蛋白质(中位数为469)。肿瘤中的活性低于正常皮质中的活性(p < 0.05)。2. 在男性中,皮质细胞溶质中的活性在所有情况下均高于相应肿瘤中的活性(p < 0.05)。在女性中,皮质和肿瘤之间的活性差异无统计学意义(p > 0.05)。3. 患者年龄范围为42至81岁(中位数为62),未发现年龄对男性或女性肾皮质或肾肿瘤中观察到的GST活性水平有影响。4. 免疫印迹和免疫组织化学研究证实,GST-α是正常皮质和肿瘤中表达的主要形式,可能占这些样品中GST活性的大部分。GST-μ和GST-φ在肿瘤和正常皮质中均有表达,虽然在某些情况下皮质中的表达水平高于肿瘤中的表达水平,但也观察到相反的情况。在GST-μ类别中,仅在一个样品(肿瘤)中检测到GST M1/M2,该样品显示GST-μ的总体表达最高。GSTM3是正常和肿瘤组织中μ类别的主要同工酶,而GTM4和GSTM5未检测到。5. 当外源性物质或细胞毒性药物是不同类别的GST的特异性底物时,这些差异可能具有功能意义。

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