Primary culture of rabbit proximal tubules as a cellular model to study nephrotoxicity of xenobiotics.

Primary culture of rabbit proximal tubules as a cellular model to study nephrotoxicity of xenobiotics.
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兔近曲小管的原代培养作为细胞模型来研究异生素的肾毒性。

DOI:
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发表时间:
1993
影响因子:
19.6
通讯作者:
C. Grimellec
C. Grimellec
中科院分区:
医学1区
文献类型:
--
作者:
Anne Blais;Juliette Morvan;Gérard Friedlander;C. Grimellec

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在兔肾上皮细胞近端小管细胞(PTC)原代培养中,研究庆大霉素处理对原位质膜结合蛋白功能的影响。在无葡萄糖培养基中培养PTC,并与氨基糖苷一起培养,测定PTC的顶端和基底侧酶活性、磷酸、葡萄糖和丙氨酸钠偶联运输系统的活性以及胞质乳酸脱氢酶(LDH)的泄漏。庆大霉素以浓度和时间依赖性的方式改变了二肽基肽酶IV (DPP IV)、中性氨基肽酶(NAP)、Na+K(+)- atp酶的活性以及钠依赖性葡萄糖和磷酸盐摄取的Vmax,而γ -谷氨酰转肽酶(GGT)和钠依赖性丙氨酸摄取未受影响。相同浓度的庆大霉素可诱导LDH渗漏和细胞功能损害。相反,在短时间暴露下,在酶活性不变的条件下,氯化汞对三种钠偶联转运系统的活性抑制程度相似。这些数据表明,虽然细胞膜流动性的改变可能介导庆大霉素对膜功能的影响,但氯化汞对运输的抑制更反映了对尖膜钠通透性的影响。他们还表明,研究原代培养的近端小管细胞中Na(+)偶联转运是一种简单而敏感的体外模型,可用于评估药物引起的肾毒性。
The effects of gentamicin treatment on functions of the plasma membrane-bound proteins in situ were investigated in primary culture of rabbit proximal tubular cells (PTC), a recognized model of renal epithelial cells. Activities of apical and basolateral enzymes, activities of phosphate, glucose and alanine sodium-coupled transport systems and leakage of the cytosolic enzyme lactate dehydrogenase (LDH) were determined in PTC grown in glucose-free culture medium as confluent monolayers and incubated with the aminoglycoside. Gentamicin altered in a concentration- and time-dependent manner the activity of dipeptidyl peptidase IV (DPP IV), neutral aminopeptidase (NAP), Na+K(+)-ATPase and the Vmax of sodium-dependent glucose and phosphate uptake, whereas gamma-glutamyl-transpeptidase (GGT) and sodium-dependent alanine uptake were unaffected. Identical concentration of gentamicin was required to induce LDH leakage and cell functions impairment. In contrast, under short time exposure, a condition where the enzyme activities were untouched, mercuric chloride inhibited to a similar extent the activity of the three sodium-coupled transport systems. These data suggest that whereas alterations in membrane fluidity might mediate the effects of gentamicin on membrane functions, the inhibition of transports by mercuric chloride rather reflects an effect on sodium permeability of the apical membrane. They also suggest that study of Na(+)-coupled transports in proximal tubular cells grown in primary culture is a simple and sensitive in vitro model to assess drug-induced nephrotoxicity.
氨基糖苷类抗生素的肾脏药理学。
DOI: 10.1159/000409975
发表时间: 1984
影响因子: --
作者:
Kaloyanides,GJ
通讯作者: Kaloyanides,GJ
庆大霉素对培养兔近端肾小管细胞磷脂代谢的影响。
DOI: 10.1152/ajpcell.1989.256.1.c204
发表时间: 1989
期刊: The American journal of physiology
影响因子: --
作者:
Ramsammy,LS;Josepovitz,C;Lane,B;Kaloyanides,GJ
通讯作者: Kaloyanides,GJ
暴露于氯化汞的 LLC-PK1 细胞中的脂质变化。
DOI: 10.1038/ki.1986.31
发表时间: 1986
影响因子: 19.6
作者:
Troyer,DA;Kreisberg,JI;Venkatachalam,MA
通讯作者: Venkatachalam,MA