Obstruction of proximal tubules initiates cytoresistance against hypoxic damage.
Obstruction of proximal tubules initiates cytoresistance against hypoxic damage.
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近端肾小管阻塞会引发细胞对缺氧损伤的抵抗。
DOI：
10.1038/ki.1995.80
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发表时间：
1995
影响因子：
19.6
通讯作者：
R. Zager
中科院分区：
文献类型：
--
作者：
R. Zager
急性肾小管坏死(ATN)后，对进一步肾损伤产生细胞抵抗。然而，这一现象的启动事件和亚细胞决定因素还没有被定义。由于肾小管梗阻是ATN的结果，这项研究评估了它是否改变了肾小管对缺氧性损伤的敏感性。为此目的，肾外梗阻(大鼠输尿管结扎)被用来分离ATN的梗阻效应。在输尿管结扎或假手术后24小时，分离皮质近端小管段(PTS)，造成缺氧(15或30分钟)/复氧损伤。由于氧化应激、细胞钙超载和磷脂酶A2攻击被认为是缺氧/复氧损伤的介质，因此我们还评估了FeS04、钙离子载体和磷脂酶A2诱导的PTS损伤的程度。在梗阻性肾脏的PTS中，由于上述每一种因素导致的细胞损伤(%LDH释放)始终较少。这种细胞抵抗：(A)不需要有尿毒症史(见单侧梗阻)；(B)它似乎与肾小管增殖反应(通过增殖细胞核抗原表达来评估)无关；(C)它不受早期肾小管修复(梗阻解除24小时不变)的影响；(D)它发生时没有增加热休克蛋白(HSP-70)或抗氧化酶(超氧化物歧化酶，过氧化氢酶)的表达。在损伤期间，受阻的PTS的腺苷酸池总量高于对照组；然而，这似乎是保护的相关性，而不是它的中介。相反，阻塞的小管表现出对PLA2攻击的质膜抵抗力的主要增加(在与外源PLA2孵育期间，阻塞的PTS的溶血磷脂酰胆碱和游离脂肪酸的生成大约比对照少3倍)。综上所述，这些结果表明：(1)肾小管梗阻保护PTS免受损伤，提示它在ATN过程中的发展可能引发细胞抵抗；以及(2)这种细胞抵抗似乎至少部分是由质膜对PLA2和潜在的其他形式的攻击(如氧化应激、胞浆钙负荷)的直接增加所介导的。
Following acute tubular necrosis (ATN), cytoresistance to further renal injury results. However, the initiating events and the subcellular determinants of this phenomenon have not been defined. Since tubular obstruction is a consequence of ATN, this study evaluated whether it alters tubular susceptibility to hypoxic damage. Extrarenal obstruction (ureteral ligation in rats) was used for this purpose to dissociate obstructive effects from those of ATN. Twenty-four hours following ureteral ligation or sham surgery, cortical proximal tubular segments (PTS) were isolated and subjected to hypoxic (15 or 30 min)/reoxygenation injury. Since oxidant stress, cell Ca2+ overload, and PLA2 attack are purported mediators of hypoxic/reoxygenation injury, degrees of FeS04, Ca2+ ionophore, and phospholipase A2-induced PTS damage also were assessed. The cell injury (% LDH release) which resulted from each of the above was consistently less in PTS obtained from obstructed kidneys. This cytoresistance: (a) did not require prior uremia to develop (seen with unilateral obstruction); (b) it did not appear to correlate with a tubular proliferative response (assessed by proliferating cell nuclear antigen expression); (c) it was uninfluenced by early tubular repair (unchanged by 24 hrs of obstruction release); and (d) it occurred without increased heat shock protein (HSP-70) or antioxidant enzyme (superoxide dismutase, catalase) expression. Total adenylate pools were higher in obstructed versus control PTS during injury; however, this appeared to be a correlate of the protection, rather than a mediator of it. In contrast, obstructed tubules manifested a primary increase in plasma membrane resistance to PLA2 attack (approximately 3-fold less lysophosphatidylcholine and free fatty acid generation in obstructed vs. control PTS during incubation with exogenous PLA2). In sum, these results indicate that: (1) tubular obstruction protects PTS from injury, suggesting that its development during ATN may initiate cytoresistance; and (2) this cytoresistance appears to be mediated, at least in part, by a direct increase in plasma membrane resistance to PLA2 and potentially other forms (such as, oxidant stress, cytosolic Ca2+ loading) of attack.
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无机铁和肌红蛋白对体外近端肾小管脂质过氧化和细胞毒性的影响。
DOI：
10.1172/jci115682
发表时间：
1992
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Zager,RA;Foerder,CA
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DOI：
--
发表时间：
1991
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
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作者：
Zager,RA;Gmur,DJ;Bredl,CR;Eng,MJ
通讯作者：
Eng,MJ
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DOI：
10.1042/cs0620667
发表时间：
1982
期刊：
Clinical science (London, England : 1979)
影响因子：
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作者：
Westenfelder,C;Crawford,PA;Hamburger,RK;Baranowski,RL;Kurtzman,NA
通讯作者：
Kurtzman,NA
影响因子：
15.9
作者：
NATH, KA;BALLA, G;ROSENBERG, ME
通讯作者：
ROSENBERG, ME
近曲小管缺氧期间 Ca2 摄取、脂肪酸和 LDH 释放：美帕林和地布卡因的影响。
DOI：
10.1152/ajprenal.1994.266.2.f196
发表时间：
1994
期刊：
The American journal of physiology
影响因子：
--
作者：
Bunnachak,D;Almeida,AR;Wetzels,JF;Gengaro,P;Nemenoff,RA;Burke,TJ;Schrier,RW
通讯作者：
Schrier,RW