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Characterization of the interaction ...

Zhen, Yueying.

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Characterization of the interaction of the human sodium pump with naturally occurring and synthetic novel inhibitors.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Characterization of the interaction of the human sodium pump with naturally occurring and synthetic novel inhibitors./
作者:	Zhen, Yueying.
面頁冊數:	120 p.
附註:	Source: Dissertation Abstracts International, Volume: 65-07, Section: B, page: 3455.
Contained By:	Dissertation Abstracts International65-07B.
標題:	Chemistry, Biochemistry. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3139021
ISBN:	9780496861729

Characterization of the interaction of the human sodium pump with naturally occurring and synthetic novel inhibitors.
Zhen, Yueying.

Characterization of the interaction of the human sodium pump with naturally occurring and synthetic novel inhibitors. - 120 p.

Source: Dissertation Abstracts International, Volume: 65-07, Section: B, page: 3455.

Thesis (Ph.D.)--Brigham Young University, 2004.

The [Na,K]-ATPase or sodium pump (SP) is a ubiquitous membrane cation transport system. Because of its potential participation in the pathophysiology of essential hypertension and cataract formation in humans, the SP is under active investigation to detail its function and control. In this dissertation, I report two novel methods of measuring SP ion transport and ATPase hydrolysis activity in intact human red blood cells. The first assay is a non-isotopic, red cell Rb-uptake assay, which provides sensitivity comparable to radioactive techniques, but eliminates the use of radioisotopes common to other Rb-uptake assay methods. The second is an intact, red cell [Na,K]ATPase hydrolysis assay, which allows direct comparisons of the effects of several inhibitors on ion transport and ATP hydrolysis. When these two methods were used to assess five naturally occurring cardioglycosides, a marked asynchronous inhibition of the two activities (hydrolysis and ion transport) was found. Moreover, the magnitude of the difference was inhibitor dependent. I also compared these assay results with data obtained from inhibition of dog kidney [Na,K]-ATPase hydrolysis and found that assessments of SP inhibitor potency made by this traditional assay that employs commercially available dog kidney [Na,K]-ATPase do not explain physiological effects in human cells. These new methods allow for more appropriate drug evaluation and drug development.

ISBN: 9780496861729Subjects--Topical Terms:

1017722
Chemistry, Biochemistry.

Characterization of the interaction of the human sodium pump with naturally occurring and synthetic novel inhibitors.
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502 $a Thesis (Ph.D.)--Brigham Young University, 2004.
520 $a The [Na,K]-ATPase or sodium pump (SP) is a ubiquitous membrane cation transport system. Because of its potential participation in the pathophysiology of essential hypertension and cataract formation in humans, the SP is under active investigation to detail its function and control. In this dissertation, I report two novel methods of measuring SP ion transport and ATPase hydrolysis activity in intact human red blood cells. The first assay is a non-isotopic, red cell Rb-uptake assay, which provides sensitivity comparable to radioactive techniques, but eliminates the use of radioisotopes common to other Rb-uptake assay methods. The second is an intact, red cell [Na,K]ATPase hydrolysis assay, which allows direct comparisons of the effects of several inhibitors on ion transport and ATP hydrolysis. When these two methods were used to assess five naturally occurring cardioglycosides, a marked asynchronous inhibition of the two activities (hydrolysis and ion transport) was found. Moreover, the magnitude of the difference was inhibitor dependent. I also compared these assay results with data obtained from inhibition of dog kidney [Na,K]-ATPase hydrolysis and found that assessments of SP inhibitor potency made by this traditional assay that employs commercially available dog kidney [Na,K]-ATPase do not explain physiological effects in human cells. These new methods allow for more appropriate drug evaluation and drug development.
520 $a Another part of my dissertation focuses on synthesized digitalis compounds. I hypothesized that the configurations of the rings would have a pronounced effect on inhibition potency. Strophanthidin was selected as the model compound and I made several chemical modifications to the steroid A and D rings. The above two assays were again applied to these synthesized compounds in addition to the traditional dog kidney [Na,K]-ATPase hydrolysis assay. The data on the synthesized compounds confirmed that the traditional dog kidney assay is a poor predictor of functional activity against intact human red blood cells. I also found that the conformation and chemical environment of C-3 position is very important for inhibition of ion transport activity, and add support to the commonly held view that 3beta-OH and its conjugated sugar chain are important.
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