ACID-BASE REGULATION OF RENAL METABOLISM

肾脏代谢的酸碱调节

• 批准号: 3152642
• 负责人: MALCOLM WATFORD
• 金额: $ 6.79万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-08-01 至 1986-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3152642
• 关键词: acid base balance; acidosis; ammonia; genetic transcription; glutamate dehydrogenase; glutaminase; kidney metabolism; messenger RNA; phosphoenolpyruvate carboxylase; renal tubular transport

The increased synthesis of ammonia and glucose by the kidney in acidosis is regulated by both short-term and long-term controls. In the short-term it is known that increased flux through the pathway in vitro can be brought about by certain hormones, a decrease in the medium pH or even the addition of serum from an acidotic animal. The long-term response to acidosis involves induction of certain key enzymes, phosphoenolpyruvate carboxykinase, glutaminase and glutamate dehydrogenase. The induction of phosphoenolpyruvate carboxykinase is known to be due to increased rates of enzyme synthesis and this correlates with increased amounts of mRNA coding for the enzyme. The mechanism by which acid-base balance can cause such changes is unknown. The aim of the work described in this application is to determine how acidosis can influence the levels of phosphoenolpyruvate carboxykinase in the kidney. The work will use both rats and chickens where differences in intracellular enzyme distribution and different regulatory patterns will allow comparison of mechanisms. The initial work will characterize the in vivo response to acidosis. Determination of extracellular signals possibly involved in the acidosis response will be carried out using isolated proximal tubule cells where changes in the concentrations of mRNA coding for phosphoenolpyruvate carboxykinase are readily detectable. Having identified extracellular agents the work will progress to understanding their intracellular mechanism of action. This will include experiments to determine if these agents act by changing transcription rates for the enzyme. The long-term goal is to determine if a common mechanism is involved in the acid-base mediated changes in the levels of a number of renal enzymes. In particular the identification of the "signal" to the kidney during acidosis is of fundamental importance to the understanding of the regulation of renal metabolism.

在酸中毒中，肾脏对氨和葡萄糖的合成增加

项目成果

The regulation of glutamine and ketone-body metabolism in the small intestine of the long-term (40-day) streptozotocin-diabetic rat.

长期（40天）链脲佐菌素糖尿病大鼠小肠谷氨酰胺和酮体代谢的调节。

• DOI: 10.1042/bj2420061
• 发表时间: 1987
• 期刊: The Biochemical journal
• 作者: Watford,M;Erbelding,EJ;Smith,EM
• 通讯作者: Smith,EM

Hormonal and acid-base regulation of phosphoenolpyruvate carboxykinase mRNA levels in rat kidney.

大鼠肾脏中磷酸烯醇丙酮酸羧激酶 mRNA 水平的激素和酸碱调节。

• DOI: 10.1016/0003-9861(90)90135-l
• 发表时间: 1990
• 期刊: Archives of biochemistry and biophysics
• 影响因子: 3.9
• 作者: Watford,M;Mapes,RE
• 通讯作者: Mapes,RE

The synthesis of glucose and ammonia by kidney tubules isolated from suckling and early-weaned lambs.

从哺乳羔羊和早期断奶羔羊身上分离出的肾小管合成葡萄糖和氨。

• DOI: 10.1016/0305-0491(87)90212-4
• 发表时间: 1987
• 期刊: Comparative biochemistry and physiology. B, Comparative biochemistry
• 作者: Watford,M;Lane,SF;Hogue,DE
• 通讯作者: Hogue,DE

Effects of metabolic acidosis and diabetes on the abundance of specific renal mRNAs.

代谢性酸中毒和糖尿病对特定肾 mRNA 丰度的影响。

• DOI: 10.1016/0020-711x(89)90187-0
• 发表时间: 1989
• 期刊: The International journal of biochemistry
• 作者: Mapes,RE;Watford,M
• 通讯作者: Watford,M

Hormonal and nutritional regulation of phosphoenolpyruvate carboxykinase mRNA levels in chicken kidney.

鸡肾磷酸烯醇丙酮酸羧激酶 mRNA 水平的激素和营养调节。

• DOI: 10.1093/jn/119.2.319
• 发表时间: 1989
• 期刊: The Journal of nutrition
• 作者: Watford,M