Proximal Tubule Function and Response to Acidosis

Curthoys, Norman P.; Moe, Orson W.

doi:10.2215/cjn.10391012

Cited by 263 publications

(216 citation statements)

References 97 publications

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“…Changes in ammoniagenesis, such as during metabolic acidosis, are associated with changes in the expression of SNAT3, but not expression of apical Na 1 -dependent neutral amino acid transporter-1 (50). Ammoniagenesis primarily involves phosphate-dependent glutaminase, glutamate dehydrogenase, a-ketoglutarate dehydrogenase, and phosphoenolpyruvate carboxykinase (PEPCK) (47,51), and complete glutamine metabolism generates two NH 4 1 and two HCO 3 2 ions per glutamine. The bicarbonate produced is then transported across the basolateral membrane via electrogenic sodium-coupled bicarbonate co-transporter, isoform 1A (NBCe-1A), and serves as "new bicarbonate" generated by the kidney.…”

Section: Renal Ammonia Handlingmentioning

confidence: 99%

Urea and Ammonia Metabolism and the Control of Renal Nitrogen Excretion

Weiner

Mitch

Sands

2015

Clinical Journal of the American Society of Nephrology

366

265

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Renal nitrogen metabolism primarily involves urea and ammonia metabolism, and is essential to normal health. Urea is the largest circulating pool of nitrogen, excluding nitrogen in circulating proteins, and its production changes in parallel to the degradation of dietary and endogenous proteins. In addition to serving as a way to excrete nitrogen, urea transport, mediated through specific urea transport proteins, mediates a central role in the urine concentrating mechanism. Renal ammonia excretion, although often considered only in the context of acidbase homeostasis, accounts for approximately 10% of total renal nitrogen excretion under basal conditions, but can increase substantially in a variety of clinical conditions. Because renal ammonia metabolism requires intrarenal ammoniagenesis from glutamine, changes in factors regulating renal ammonia metabolism can have important effects on glutamine in addition to nitrogen balance. This review covers aspects of protein metabolism and the control of the two major molecules involved in renal nitrogen excretion: urea and ammonia. Both urea and ammonia transport can be altered by glucocorticoids and hypokalemia, two conditions that also affect protein metabolism. Clinical conditions associated with altered urine concentrating ability or water homeostasis can result in changes in urea excretion and urea transporters. Clinical conditions associated with altered ammonia excretion can have important effects on nitrogen balance.

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Section: Renal Ammonia Handlingmentioning

confidence: 99%

Urea and Ammonia Metabolism and the Control of Renal Nitrogen Excretion

Weiner

Mitch

Sands

2015

Clinical Journal of the American Society of Nephrology

366

265

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“…Because this has been recently reviewed in this series (18), only a few comments will be made. The signals for these changes are often thought to be pH per se, either intracellular or extracellular.…”

Section: Regulation Of Hco 3 2 Reabsorption In the Proximal Tubulementioning

confidence: 99%

“…have also been shown to alter NH 3 production. The enzymatic and transporter changes that facilitate enhanced ammoniagenesis during acidosis have recently been reviewed in this series (18). The transport of the produced NH 4 1 along the nephron and into the urine is a complex process that is still a topic of intense study (Figure 6).…”

Section: Nhmentioning

confidence: 99%

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Acid-Base Homeostasis

Hamm¹,

Nakhoul²,

Hering-Smith³

2015

Clinical Journal of the American Society of Nephrology

336

262

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Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO 3 2 and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO 3 2 is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys.

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“…36,37) The proximal tubule contributes to fluid, electrolyte, and nutrient homeostasis by reabsorbing 60-70% of the water and NaCl, 70-80% of the phosphate, and nearly all of the nutrients (i.e., glucose, amino acids) in the ultrafiltrate. 66,67) In the proximal tubules, ezrin is concentrated at cell surface structures such as microvilli in the wild-type kidney. 68) In our study, the Vil2 KD/KD mouse kidney showed no obvious histological differences from the wild-type mouse kidney.…”

Section: Kidneymentioning

confidence: 99%

Pathophysiological Roles of Ezrin/Radixin/Moesin Proteins

Kawaguchi

Yoshida

Hatano

et al. 2017

Biological & Pharmaceutical Bulletin

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Ezrin/radixin/moesin (ERM) proteins function as general cross-linkers between plasma membrane proteins and the actin cytoskeleton and are involved in the functional expression of membrane proteins on the cell surface. They also integrate Rho guanosine 5′-triphosphatase (GTPase) signaling to regulate cytoskeletal organization by sequestering Rho-related proteins. They act as protein kinase A (PKA)-anchoring proteins and sequester PKA close to its target proteins for their effective phosphorylation and functional regulation. Therefore, ERM proteins seem to play important roles in the membrane transport of electrolytes by ion channels and transporters. In this review, we focus on the pathophysiological roles of ERM proteins in in vivo studies and introduce the phenotypes of their knockout and knockdown mice.Key words ezrin/radixin/moesin protein; cytoskeleton; knockout mouse EZRIN/RADIXIN/MOESIN PROTEINS REGULATE CYTOSKELETAL ORGANIZATION BY CROSS-LINK-ING PLASMA MEMBRANES WITH THE ACTIN CY-TOSKELETON AND INTEGRATING RHO GTPASE SIGNALINGThe ezrin, radixin, and moesin (ERM) proteins are general cross-linkers between cortical actin filaments and plasma membranes. They are concentrated at cell surface structures such as microvilli, filopodia, uropods, ruffling membranes, retraction fibers, and cell adhesion sites where actin filaments are associated with plasma membranes, but not along cytoplasmic actin filaments such as stress fibers.1) ERM proteins also integrate Rho guanosine 5′-triphosphatase (GTPase) signaling to regulate cytoskeletal organization by sequestering Rhorelated proteins.2) The apparent molecular mass of ERM is 82, 80, and 75 kDa, respectively. They show high amino acid identity, especially in their amino-and carboxy-terminal domains. Their amino-terminal domains consisting of ca. 300 amino acid residues are termed "the band four point one and ERM (FERM) domain" because their amino acid sequences are conserved within ERM proteins and the erythrocyte band 4.1 protein (Fig. 1). FERM domains are also found in numerous membrane-associated signaling and cytoskeletal proteins such as talin.3) The FERM domains, which are composed of three structural modules (F1, F2, and F3), together form a compact clover-shaped structure 4,5) and bind to integral membrane proteins, [6][7][8][9][10][11][12][13][14][15][16] scaffold proteins, [17][18][19][20] and the Rho-related proteins (such as the Rho-guanosine 5′-diphosphate (GDP)-dissociation inhibitor [Rho-GDI] and Dbl) 21,22) listed in Table 1, as well as to phosphatidylinositol 4,5-bisphosphate (PIP 2 ). 12) The scaffold proteins Na + /H + exchanger regulatory factors (NHERF) 1 and 2, which contain two PDZ (PSD-95, Discs-large, and ZO-1) domains, bind to the FERM domain at the carboxy-terminus. 17,20) These PDZ domains on the NHERFs interact with the PDZ-binding motif of membrane proteins such as the cystic fibrosis transmembrane conductance regulator (CFTR) and Na 19,25,26) On the other hand, the carboxy-terminal domains, especially 34 amino acid residues, are also h...

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Proximal Tubule Function and Response to Acidosis

Cited by 263 publications

References 97 publications

Urea and Ammonia Metabolism and the Control of Renal Nitrogen Excretion

Urea and Ammonia Metabolism and the Control of Renal Nitrogen Excretion

Acid-Base Homeostasis

Pathophysiological Roles of Ezrin/Radixin/Moesin Proteins

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