Substrate-dependent differential regulation of mitochondrial bioenergetics in the heart and kidney cortex and outer medulla

Maturation and systemic acidosis are two factors that stimulate urinary acidification. Proton secretion, CO2 handling, and some metabolic processes are facilitated by cytosolic carbonic anhydrase (CA). The activity of this enzyme in kidney, red blood cells (RBCs), and liver could be regulated in response to acid-base perturbations or maturation. Therefore, we investigated the effects of maturation and NH4Cl acid loading on soluble CA hydratase activity in RBCs, kidneys, and livers of female New Zealand White rabbits during three stages of maturation (neonatal, 4 wk, and adult). Total RBC CA activity doubled with maturation but did not increase after NH4Cl loading. There was substantial interindividual variation in the amount of CA I related activity. In the kidney we found intrinsic cortical CA II activity to be more than twice that in the outer medulla, which was more than twice that in the inner medulla. CA activity doubled with maturation in the cortex and increased by 70% in the outer medulla. Twenty hours after an NH4Cl load there was a 50% increase in renal cortical CA activity in 4-wk-old rabbits, but a comparable increase in cortical CA activity was only seen after 3-5 days of NH4Cl loading in adult animals. In the liver a third of cytosolic CA activity was acetazolamide resistant, presumably CA III, which doubled with maturation. Chronic NH4Cl loading in adult animals induced an almost 60% increase in hepatic acetazolamide-sensitive CA activity (mostly CA II). These data show that in the rabbit there is a renal corticomedullary gradient in soluble CA activity (mostly CA II), with significant activity in the inner medulla. Maturation induced total CA activity in the inner medulla. Maturation induced total CA activity in RBCs, CA II activity in kidney cortex and outer medulla, and CA III in the liver. Finally, CA II activity in kidney cortex and liver appeared to be regulated in response to some conditions of NH4Cl loading.

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Differential regulation of ROMK expression in kidney cortex and medulla by aldosterone and potassium

AJP Renal Physiology ◽

10.1152/ajprenal.1998.275.2.f239 ◽

1998 ◽

Vol 275 (2) ◽

pp. F239-F245 ◽

Cited By ~ 28

Author(s):

H. Wald ◽

H. Garty ◽

L. G. Palmer ◽

M. M. Popovtzer

Keyword(s):

Rat Kidney ◽

Differential Regulation ◽

Kidney Cortex ◽

High K ◽

Atpase Subunits ◽

Inwardly Rectifying ◽

Intact Rats

This study explores the role of K+ and aldosterone in the regulation of mRNA of the ATP-sensitive, inwardly rectifying K+ channel, ROMK, in the rat kidney. K+ deficiency downregulated ROMK mRNA in cortex to 47.1 ± 5.1% of control ( P < 0.001) and in medulla to 56.1 ± 3.4% ( P < 0.001). High-K+ diet slightly increased ROMK mRNA in medulla to 122 ± 9% ( P < 0.05 vs. control). Adrenalectomy (Adx) downregulated cortical ROMK mRNA to 30.7 ± 6.8% ( P < 0.001 vs. control), and increased it in medulla to 138 ± 12.9% ( P < 0.02 vs. control). In Adx rats, K+ deficiency decreased ROMK mRNA in cortex and medulla similar to intact rats. The α1- and β1-Na-K-ATPase subunits were regulated in parallel to that of ROMK. In medulla, ROMK mRNA correlated with serum K+ concentration at R = 0.9406 ( n = 6, P < 0.001) and α1-Na-K-ATPase mRNA at R = 0.9756 ( n = 6, P < 0.001). ROMK2 also correlated with serum K+ concentration ( R = 0.895; n = 6, P < 0.01). These results show that cortical ROMK expression is regulated by aldosterone and K+, whereas the medullary ROMK mRNA is regulated by serum K+.

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Cyclophosphamide-induced renal damage in nude mice prevented by traditional Chinese medicine (TCM) herbal mixture LQ.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e22210 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e22210-e22210

Author(s):

Chengyu Wu ◽

Lei Zhang ◽

Robert M. Hoffman

Keyword(s):

Renal Damage ◽

Renal Toxicity ◽

Kidney Cortex ◽

Thick Ascending Limb ◽

Loop Of Henle ◽

Outer Medulla ◽

Herbal Mixture ◽

Pretreated Group ◽

Convoluted Tubules ◽

Normal Architecture

e22210 Background: Renal damage is a dose-limiting side effects of cyclophosphamide (CYC). In the current study, we determined if a TCM herbal mixture LQ could be protective against CYC renal toxicity. Methods: Mice were treated with CYC or CYC+LQ. The histology of each organ was observed under microscopy after H&E staining. Results: The histology of the heart, liver, spleen, lung and intestine showed normal histopathological structure in all groups. The kidney of the CYC-treated mice showed toxicity including the glomeruli, the tubules, and the interstitium. The structures of the cortex in CYC pretreated group showed a disconnection between glomeruli and tubules. The ducts in the medulla were destroyed. In contrast, the kidneys in the control mice, LQ-treated mice, and CYC+LQ-treated mice showed normal architecture of the kidney cortex and medulla. In the untreated controls and the CYC+LQ-treated mice, the cortex showed normal renal corpuscles, proximal convoluted tubules, and distal convoluted tubules. The inner medulla and outer medulla all contained a thick ascending limb of the loop of Henle, and interstitial connective tissue. LQ also protected against weight loss and cachexia induced by CYC. Conclusions: TCM is a promising for combination with CYC to reduce toxicity.

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Cellular and subcellular localization of enzymes of arginine metabolism in rat kidney

Biochemical Journal ◽

10.1042/bj2820369 ◽

1992 ◽

Vol 282 (2) ◽

pp. 369-375 ◽

Cited By ~ 43

Author(s):

S N Dhanakoti ◽

M E Brosnan ◽

G R Herzberg ◽

J T Brosnan

Keyword(s):

Rat Kidney ◽

Subcellular Fractionation ◽

Kidney Cortex ◽

Ornithine Aminotransferase ◽

Outer Medulla ◽

Argininosuccinate Synthase ◽

Distal Tubules ◽

Convoluted Tubules ◽

Inner Cortex ◽

Proximal Convoluted Tubules

Rat kidneys extract citrulline derived from the intestinal metabolism of glutamine and convert it stoichiometrically into arginine. This pathway constitutes the major endogenous source of arginine. We investigated the localization of enzymes of arginine synthesis, argininosuccinate synthase and lyase, and of breakdown, arginase and ornithine aminotransferase, in five regions of rat kidney, in cortical tubule fractions and in subcellular fractions of cortex. Argininosuccinate synthase and lyase were found almost exclusively in cortex. Arginase and ornithine aminotransferase were found in inner cortex and outer medulla. Since cortical tissue primarily consists of proximal convoluted and straight tubules, distal tubules and glomeruli, we prepared cortical tubule fragments by collagenase digestion of cortices and fractionated them on a Percoll gradient. Argininosuccinate synthase and lyase were found to be markedly enriched in proximal convoluted tubules, whereas less than 10% of arginase and ornithine aminotransferase, were recovered in this fraction. Arginine production from citrulline was also enriched in proximal convoluted tubules. Subcellular fractionation of kidney cortex revealed that argininosuccinate synthase and lyase are cytosolic. We therefore conclude that arginine synthesis occurs in the cytoplasm of the cells of the proximal convoluted tubule.

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Altered expression of COX-1, COX-2, and mPGES in rats with nephrogenic and central diabetes insipidus

AJP Renal Physiology ◽

10.1152/ajprenal.00114.2004 ◽

2005 ◽

Vol 288 (5) ◽

pp. F1053-F1068 ◽

Cited By ~ 50

Author(s):

Primož Kotnik ◽

Jakob Nielsen ◽

Tae-Hwan Kwon ◽

Ciril Kržišnik ◽

Jørgen Frøkiær ◽

...

Keyword(s):

Diabetes Insipidus ◽

Wistar Rats ◽

Differential Regulation ◽

Water Reabsorption ◽

Outer Medulla ◽

Altered Expression ◽

Bb Rats ◽

Cox 2 ◽

Cox 1 ◽

Model Expression

Prostaglandins have an important role in renal salt and water reabsorption. PGE2 is the main kidney prostaglandin and is thought to be mainly produced in the kidney inner medulla (IM). There are indications that PGE2 synthesis in nephrogenic (NDI) and central (CDI) diabetes insipidus is altered. We hypothesize that the expression of the major PGE2 synthesis enzymes cyclooxygenases 1 and 2 (COX-1, COX-2) and membrane-associated PGE2 synthase (mPGES) is altered in the kidneys of rats with NDI and CDI. Wistar rats treated with lithium for 4 wk were used as the NDI model. One-half of the NDI model rats were additionally dehydrated for 48 h. Brattleboro (BB) rats that lack endogenous antidiuretic hormone were used as the CDI model. Expression and localization of COX-1, COX-2, and mPGES in IM, inner stripe of outer medulla (ISOM), and cortex were determined by immunoblotting and immunohistochemistry. In lithium-induced NDI, expression of COX-1, COX-2, and mPGES was markedly decreased in IM. In ISOM and cortex, COX-1 expression was marginally reduced and mPGES expression was unaltered. COX-2 expression was undetected in ISOM and marginally increased in cortex. Consistent with this, the density of COX-2-expressing cells in macula densa was significantly increased, indicating differential regulation of COX-2 in IM and cortex. Dehydration of NDI rats resulted in a marked increase in COX-2 immunolabeling in IM interstitial cells, and there was no significant change in COX-1 and mPGES expression in any kidney zone. Treatment of DDAVP in BB rats for 6 days resulted in a markedly increased expression of COX-1, COX-2, and mPGES in IM. In the cortex, there were no changes in the expression of COX-1 and mPGES, whereas COX-2 expression was decreased. These results identify markedly reduced expression of COX-1, COX-2, and mPGES in IM in lithium-induced NDI. Furthermore, there were major changes in the expression of COX-1, COX-2, and mPGES in rats with CDI.

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Protein kinase inhibition differentially regulates organic cation transportThis article is one of a selection of papers published in a special issue celebrating the 125th anniversary of the Faculty of Medicine at the University of Manitoba.

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y09-072 ◽

2009 ◽

Vol 87 (10) ◽

pp. 821-830 ◽

Cited By ~ 2

Author(s):

Alexander M. Gerlyand ◽

Daniel S. Sitar

Keyword(s):

Adenylyl Cyclase ◽

Organic Cation ◽

Kidney Tissue ◽

Organic Cation Transporter ◽

Diabetic Rats ◽

Differential Regulation ◽

Transport Systems ◽

Kidney Cortex ◽

Cellular Transport ◽

Soluble Adenylyl Cyclase

Previous studies showed that amantadine transport increased while tetraethylammonium (TEA) transport decreased in kidney tissue from diabetic rats. Changes in transport activity were reversed by exogenous insulin. We hypothesized that this difference in transport regulation is due to differential regulation of different transport systems. Native human embryonic kidney cortex cells (HEK293 cell line) and rat organic cation transporter (rOCT)-transfected cells were used to test the hypothesis. In support of differential regulation, short-term glucose starvation stimulated amantadine transport and inhibited TEA transport, but the effect was bicarbonate-modulated only for amantadine. cAMP analogues inhibited TEA transport while stimulating amantadine transport. This effect was additive to the effect of insulin, and the presence of bicarbonate affected the extent of the change. Our findings indicated that regulation of rOCT 1 and 2 was mediated by transmembrane adenylyl cyclase, and regulation of amantadine transport was mediated by soluble adenylyl cyclase, suggesting that intracellular microdomains of cAMP may be important in determining overall cellular transport for organic cations. Soluble adenylyl cyclase activity is known to be modulated by bicarbonate and lactate. These observations support our hypothesis and reconcile our previous studies demonstrating increased transport affinity for amantadine in the presence of bicarbonate and decreased transport affinity in the presence of lactate.

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Measurement and Distribution of Zinc, Cadmium, and Mercury in Human Kidney Tissue

Clinical Chemistry ◽

10.1093/clinchem/18.1.67 ◽

1972 ◽

Vol 18 (1) ◽

pp. 67-72 ◽

Cited By ~ 36

Author(s):

Hugh D Livingston

Keyword(s):

Neutron Activation ◽

Gamma Spectrometry ◽

Kidney Tissue ◽

Germanium Detector ◽

Human Kidney ◽

Kidney Cortex ◽

Outer Cortex ◽

Tissue Slices ◽

Outer Medulla ◽

Zinc Cadmium

Abstract Simultaneous analyses of human kidney cortex tissues for zinc, cadmium, and mercury were made by neutron activation combined with either radiochemical separation prior to counting or direct germanium detector gamma spectrometry. For some samples from adults and infants, analyses were made on successive tissue slices from the outer cortex to the inner medulla. Zinc and cadmium show a concentration gradient, with the highest concentrations at the outer medulla. Mercury was preferentially concentrated deeper in the cortex. All three metals, and especially cadmium, are found in higher concentrations in adult than in infant kidneys. A mechanism for the rapid increase in renal cadmium is proposed. The heterogeneous renal distribution of the elements indicates that careful sampling is necessary in any comparative study of their occurrence in human kidney tissue.

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Expression of carbonic anhydrase IV mRNA in rabbit kidney: stimulation by metabolic acidosis

AJP Renal Physiology ◽

10.1152/ajprenal.1997.272.4.f551 ◽

1997 ◽

Vol 272 (4) ◽

pp. F551-F560 ◽

Cited By ~ 9

Author(s):

C. A. Winkler ◽

A. M. Kittelberger ◽

G. J. Schwartz

Keyword(s):

Metabolic Acidosis ◽

Collecting Duct ◽

Statistical Significance ◽

Sodium Dodecyl ◽

Northern Analysis ◽

Rabbit Kidney ◽

Kidney Cortex ◽

Carbonic Anhydrases ◽

Outer Medulla ◽

Reading Frame

The renal carbonic anhydrases, CA II (cytosolic) and CA IV (membrane bound), are believed to facilitate renal acid secretion. We have recently shown that renal cortical sodium dodecyl sulfate (SDS)-resistant hydratase (presumably CA IV) activity was stimulated 241% during chronic metabolic acidosis (CMA). In the present study, we examined the expression and regulation of CA IV mRNA in kidneys from control and acidotic rabbits. To obtain a CA IV probe, we reverse transcribed rabbit kidney total RNA and amplified a approximately 780-base pair (bp) DNA product using primers derived from the human CA IV sequence. Using this product, we screened one-half of a kidney cortex cDNA library and sequenced a 1,194-bp cDNA, which contained the entire open-reading frame of rabbit CA IV. The cDNA was 78% identical to human and 71% to rat CA IV. The deduced amino acid sequence projected an active zinc binding site and two glycosylation sites. Northern analysis yielded a single transcript of approximately 1,600 bp in size expressed more abundantly in cortex and inner medulla than in outer medulla. CA IV mRNA was also expressed abundantly in lung but not in liver or spleen. The high abundance of CA IV mRNA in inner medulla was localized by in situ hybridization to medullary collecting duct cells. Rabbits exposed to CMA showed significant upregulation of CA IV mRNA expression in kidney cortex and outer medulla. Despite a numerical increase, excessive variability precluded statistical significance in the inner medulla. Thus CA IV mRNA was expressed abundantly in kidney and stimulated by CMA, similar to what has been previously observed for SDS-resistant hydratase (presumed CA IV) activity. It is likely that the regulation of CA IV mRNA and activity is relevant to the kidney's adaptation to CMA.

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