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A Aperia

Publications and source records attributed to A Aperia.

At least 73 records · Page 4Linked to original sources
PubMed1995

Evidence for a role of protein phosphatases 1 and 2A during early nephrogenesis.

Although most transcriptional events appear to be modulated by reversible protein phosphorylation, little is known about the role of this regulatory system during the development of mammalian organs. Here we have studied the serine/threonine protein phosphatases (PP) 1 and 2A in the early embryonic rat kidney with regard to expression and effects on growth and differentiation. All isoforms of PP-1 and PP-2A were ubiquitously expressed in 15-day embryonic (E15) kidneys (in situ hybridization studies). In contrast, mRNA for inhibitor-1 (I-1), an endogenous inhibitor of PP-1, was detected only in undifferentiated stem cells in the outer cortical area. I-1 is a novel marker for these cells. The abundance of the PP-1 protein, confirmed with immunoblotting, was high in the embryonic kidney. In organ culture of E13 kidneys, okadaic acid (OA), an exogenous inhibitor of PP-1 and PP-2A, dose-dependently inhibited growth and nephron formation (apparent half-maximal effect at 6 nM). OA 10 nM had little effect on the growth of cultured E15 kidneys, whereas nephron formation was disturbed and morphological evidence of apoptosis was seen. In summary, this study points towards important roles for protein phosphatases 1 and/or 2A in regulation of mitogenic activity in the early embryonic kidney.

Animals↗
PubMed1995

Protein phosphatase-1 in the kidney: evidence for a role in the regulation of medullary Na(+)-K(+)-ATPase.

Previous studies of hormonal regulation of renal Na(+)-K(+)-ATPase have indicated that the activity of the sodium pump is regulated by phosphorylation-dephosphorylation reactions. Here we report that okadaic acid (OA) and calyculin A (CL-A), inhibitors of protein phosphatase (PP)-1 and PP-2A, inhibited Na(+)-K(+)-ATPase activity in cells from the rat thick ascending limb (TAL) of loop of Henle in a dose-dependent manner. CL-A was 10-fold more potent than OA. On the basis of the inhibitory constant values of CL-A and OA for PP-1 and PP-2A, it is concluded that the tubular effect is mainly due to inhibition of PP-1. In situ hybridization studies with oligonucleotide probes revealed very strong PP-1 alpha and PP-1 gamma 1 mRNA labeling in the outer stripe of the outer medulla, strong labeling in the inner stripe of the outer medulla, and weak labeling in the inner medulla. Very weak labeling was demonstrated in the outer cortex. PP-1 beta mRNA labeling was very strong in the inner stripe of the outer medulla, whereas the outer stripe had weaker labeling, and the inner medulla had weak labeling. PP-1 alpha, PP-1 beta, and PP-1 gamma 1 mRNA were also demonstrated in the transitional epithelium of the ureter. The abundance of the PP-1 alpha and PP-1 gamma isoforms as measured by immunoblotting was very high in tissue from the outer medulla, which also has a high abundance of the endogenous dopamine-regulated PP-1 inhibitor, DARPP-32.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[The 1994 Nobel Prize: discovery and significance of G-proteins].

Exactly how a cell responds to a hormone or transmitter substance depends on at least three factors: which type of receptors the cell has, which G-proteins are present and which amplifying system exists in precisely that cell. This means that the number of possible signalling pathways becomes extremely great. Here lies the most important aspect of the discoveries that have been rewarded with this year's Nobel prize. The translation of a message from an extracellular signal to an altered cellular function demands reoperation between a cascade of different proteins. One cell has one certain structure, another contains quite different components. In this manner, a limited number of signals and signal-transmitting molecules may be combined to produce extremely varied signalling pathways. Life is characterized by simplicity in design and colossal variation in form. The G-proteins' role in signal transmission in the cell is a shining example of this principle of variations on a theme that achieve the diversity necessary to maintain life.

Animals↗
PubMed1994

Activation/deactivation of renal Na+,K(+)-ATPase: a final common pathway for regulation of natriuresis.

Renal sodium metabolism, a major determinant of blood pressure, is regulated with great precision by a variety of endocrine, autocrine, and neuronal factors. Although these factors are known to regulate sodium metabolism by affecting the rate of tubular sodium reabsorption, the molecular mechanisms by which they act are poorly understood. Na+,K(+)-ATPase plays a pivotal role for sodium reabsorption in all tubular segments. The activity of this enzyme can be dynamically regulated by phosphorylation and dephosphorylation. Here we summarize both old and new evidence that several major substances believed to be involved in the regulation of sodium metabolism and blood pressure, i.e., the antidiuretic agents angiotensin II and norepinephrine, and the diuretic agents dopamine and atrial natriuretic peptide (ANP), may achieve their effects through a common pathway that involves reversible activation/deactivation of renal tubular Na+,K(+)-ATPase. Regulation of Na+,K(+)-ATPase activity was studied using a preparation of single proximal tubule (PT) segments, dissected from rat kidneys. Na+,K(+)-ATPase activity was stimulated by angiotensin II and the alpha-adrenergic agonist, oxymetazoline, at physiological, nonsaturating Na+ concentrations. These stimulatory effects were blocked by dopamine and ANP as well as by their respective second messengers, cAMP and cGMP. They were also blocked by the specific protein phosphatase 2B inhibitor FK506. These results indicate that regulation of sodium excretion by norepinephrine, angiotensin II, dopamine, and ANP can be accounted for by a bidirectionally regulated intracellular protein phosphorylation cascade that modulates the activity of renal tubular Na+,K(+)-ATPase.

Angiotensin II↗
PubMed1994

Functional parameters and 99mtechnetium-dimercaptosuccinic acid scan in acute pyelonephritis.

The diagnostic value of 99mtechnetium-dimercaptosuccinic acid (DMSA) scintigraphy, ultrasonography and renal functional parameters [urine N-acetyl-beta-D-glucosaminidase (NAG)/creatinine and urine albumin/creatinine quotients] in acute pyelonephritis (APN) were studied in 39 children (28 girls, 11 boys, median age 9 months, range 2 weeks to 9.4 years, 28 patients < 1 year, 11 patients > 1 year) with first-time urinary tract infection. Ultrasonography of the urinary tract was performed on admission and together with DMSA scintigraphy (< 10 days from admission). Urine NAG/creatinine and urine albumin/creatinine quotients were measured daily and after 6-8 weeks. Ultrasonography revealed abnormalities in 12 of 39 (31%) patients [11/32 patients (34%) with positive DMSA scintigraphy], while DMSA uptake defects were present in 32 of 39 (82%) patients [21/28 < 1 year (75%), 11/11 > 1 year (100%), P = 0.08]. Urine NAG/creatinine and urine albumin/creatinine quotients were significantly higher in children < 1 year with APN, as well as in non-renal fever controls, than in older children. However, in both age groups the urine NAG/creatinine and urine albumin/creatinine quotients were significantly higher in APN than in non-renal fever. The urine NAG and albumin excretion decreased rapidly after the initiation of antimicrobial therapy and had normalized at 6-8 weeks. The size and grade of the DMSA uptake defect (DMSA score) did not correlate with duration of disease at admission, maximum C-reactive protein or maximum fever. The urine NAG/creatinine quotient in the children < 1 year showed, however, a significant correlation with the DMSA score (r = 0.58, P < 0.05), while no correlation was found in the older children. We conclude that DMSA scintigraphy is a sensitive method to confirm the clinical diagnosis of APN, although a substantial number of infants appear to have normal scans. Early determination of the urine NAG/creatinine and albumin/ creatinine quotients may further improve the diagnostics in the infant.

Acetylglucosaminidase↗
PubMed1994

Coexisting NPY and NE synergistically regulate renal tubular Na+, K(+)-ATPase activity.

The sympathetic renal nerves are of central importance for the regulation of sodium balance. Sodium excretion decreases following renal nerve activation and increases following denervation. These effects have been attributed to norepinephrine (NE) acting on alpha-adrenergic receptors. In the present study, using isolated permeabilized rat renal proximal convoluted tubule (PCT) cells, neuropeptide Y (NPY) was shown to stimulate Na+, K(+)-ATPase activity. This 36-amino acid peptide is a messenger molecule in the sympathetic nervous system which is co-stored with NE and dopamine-beta-hydroxylase (DBH), the NE synthesizing enzyme in the renal nerves. The effect is likely to be mediated via the NPY Y2 receptor, a pertussis toxin (PTX)-sensitive G-protein, and calcium. It is partially antagonized by alpha-adrenergic antagonists, and enhanced by the subthreshold doses of alpha-adrenergic agonists. Our results suggest an important role for this peptide in the regulation of the sodium balance in the kidney.

Animals↗
PubMed1994

Neonatal kidney, fluids, and electrolytes.

Numerous clinical studies during the past two decades have indicated that kidney function and regulation of electrolyte and fluid balance undergo profound changes in the neonatal period. The genetic mechanisms behind these developmental changes have recently been the topic for many investigations and has led to the identification of factors, reviewed here, that seem to be of extraordinary importance for the induction of kidney differentiation and maturation. For a long time it has been debated whether immaturity of renal function might have any clinical consequences. It now seems clear that at least one aspect of renal immaturity, namely the high urinary sodium excretion in preterm infants, which often results in negative sodium balance, should be paid more attention to because it might interfere with growth. Two recent review articles discuss this issue. The profound changes in fluid and electrolyte homeostasis that occur in the neonatal period, involves most tissues. This is exemplified with some recent exciting studies on the changes in ion transport that occur in the lung around birth.

Humans↗
PubMed1994

Dopamine action and metabolism in the kidney.

Dopamine is one of the major natriuretic hormone. It acts as an autocrine or paracrine factor to inhibit Na+ transport in several tubular segments. Na+,K(+)-ATPase is an important target protein for dopamine. Studies of the tubular effects of dopamine have provided new information about the coupling of dopamine to intracellular signaling systems and about the molecular mechanism for dopamine interaction with other hormones. Several lines of evidence now suggest that abnormalities of the renal dopamine system can lead to salt-sensitive hypertension.

Animals↗
PubMed1994

Increased renal metabolism in diabetes. Mechanism and functional implications.

The coupling between the Na+/glucose cotransporter and Na(+)-K(+)-ATPase (NKA) described for epithelial cells (1) prompted us to study in rats with streptozocin-induced diabetes the effect of increased tubular glucose load on tubular Na+ reabsorption, NKA-dependent O2 consumption (QO2), and NKA activity. Filtered glucose is mainly reabsorbed in the proximal tubuli via the phlorizin-sensitive Na+/glucose cotransporter. In this study, the diabetic rats had a significantly higher renal blood flow (RBF), glomerular filtration rate (GFR), and Na+ reabsorption than the control rats. Total renal QO2 as well as QO2 in cortical tissue, which consists mainly of proximal tubular cells, was significantly higher in diabetic than in control rats. The increase in tissue QO2 was entirely caused by increased NKA-dependent QO2. NKA activity, measured as rate of ATP hydrolysis, was increased in cortical tubular but not glomerular tissue from diabetic rats. Phlorizin treatment abolished the increase in NKA activity, Na+ reabsorption, and QO2, as well as the increase in RBF and GFR in diabetic rats. We conclude that diabetes is associated with increased renal O2 metabolism secondary to the increase in coupled Na+ reabsorption via the Na+/glucose cotransporter and NKA. The increased oxygen consumption might contribute to the hyperperfusion and hyperfiltration in the diabetic kidney.

Adenosine Triphosphate↗
PubMed1993

Bidirectional regulation of Na+,K(+)-ATPase activity by dopamine and an alpha-adrenergic agonist.

Catecholamines have pronounced effects on the renal handling of sodium and water, dopamine-promoting sodium and water excretion, and norepinephrine-promoting sodium and water retention. In the present study, using isolated permeabilized renal tubule cells and intact rats, we have shown that these effects can be attributed to opposing actions of these transmitters on renal tubular Na+,K(+)-ATPase activity. The ability of each of these catecholamines to regulate Na+,K(+)-ATPase activity is affected by the concentration of Na+ as well as by the absence or presence of the opposing catecholamine.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Salt-deficient diet and early weaning inhibit DNA synthesis in immature rat proximal tubular cells.

A maturational gradient exists between the inner and the outer cortical nephrons in infant rats. This study compares the putative growth-retarding effects of early weaning (EW) and a salt-deficient (SD) diet in proximal tubule (PT) cells in the inner and the outer cortex. The mitotic response was measured as tritiated-thymidine incorporation in PT cells from 18- to 22-day-old rats. Under basal conditions the mitotic index is the same in the inner and the outer cortex. EW retarded body growth, but had no significant effect on the kidney/body weight (KW/BW) ratio. EW caused a significant decrease in DNA synthesis in both the outer and the inner cortical PT cells, but the effect was significantly more pronounced in the outer cortex. The SD rats had significantly lower levels of serum sodium, lower urinary sodium excretion, slightly decreased BW, but no differences in KW/BW ratio or in dry/wet KW. SD caused a decrease in DNA synthesis in the PT cells in the outer cortex, but not in the inner cortex. In conclusion, two manipulations that can retard proliferation of PT cells, i.e. EW and a SD diet, have a more pronounced effect in immature than in mature PT cells.

Aging↗
PubMed1993

Distribution of dopamine- and cAMP-dependent phosphoprotein (DARPP-32) in the developing and mature kidney.

DARPP-32 is a dopamine- and cAMP-regulated inhibitor of protein phosphatase-1 (PP-1). Dopamine and DARPP-32 regulate sodium reabsorption in renal tubules by inhibiting the activity of Na+,K(+)-ATPase. We here report the pre- and postnatal distributions of DARPP-32 in the kidney as demonstrated by immunoblotting and immunohistochemistry. With immunoblotting we examined the abundance of DARPP-32 and the functionally similar but more widespread inhibitor of PP-1, inhibitor-1 (I-1). We compared their relative abundance in the renal cortex, renal medulla and neostriatum from the brain, where DARPP-32 is greatly enriched. DARPP-32 levels in the adult rat were fourfold higher in the neostriatum than in the renal medulla and 13-fold higher than in the renal cortex. I-1 levels were approximately the same in the neostriatum and in the renal medulla and 2.5-fold higher in neostriatum than in the renal cortex. Between postnatal day 10 (PN10) and 40 (PN40) DARPP-32 abundance increased 1.3-fold in the neostriatum, 1.4-fold in the renal cortex and sixfold in the medulla. The abundance of I-1 did not increase in the striatum from PN10 to PN40 but increased 1.5-fold in the renal cortex and threefold in the renal medulla. Thus, during the time of maturation of tubular transport function, the levels of both PP-1 inhibitors increased in the kidney, the largest increase being found in the renal medulla. With immunohistochemistry strong DARPP-32-like-immunoreactivity (DARPP-32-LI) was detected in the ureteral buds from gestational day 18 and up to postnatal day 8 when nephrogenesis was completed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Catechol-O-methyltransferase mRNA in the kidney and its appearance during ontogeny.

Catechol-O-methyltransferase (COMT), primarily present as a soluble cytosolic form (S-COMT), inactivates catechols. The recent cloning of the rat and human S-COMT from placenta has allowed us to synthesize complementary oligonucleotide probes to study the localization of COMT mRNA during development in the rat kidney and in the adult human kidney using in situ hybridization histochemistry. In the adult rat kidney, COMT mRNA was detected in segment S3 of proximal tubule cells in the outer stripe of the outer medulla, and thick ascending limb of loop of Henle (TAL) in the inner stripe. COMT mRNA was detected in the prenatal rat kidney as early as on day 18. In the human kidney, strong hybridization signal was seen in the medulla and in tubule segments of the cortex. In the adult rat kidney, COMT mRNA was in addition demonstrated in the transitional epithelium of the ureter. The results suggest synthesis of COMT and inactivation of catechols along the distal parts of proximal tubules, in TAL cells, and in the epithelium of the ureter.

Aging↗
PubMed1993

Renal function in sick, very low-birth-weight infants.

Renal immaturity is pronounced in very low-birth-weight infants with a gestational age < or = 30 weeks. We attempted to elucidate if conditions requiring mechanical ventilation, including patent ductus arteriosus, might further compromise renal function due to decreased renal perfusion. Forty infants studied between 4 and 28 days of age were divided into four groups: Control with no patent ductus or mechanical ventilation (n = 8); PDA+MV, with both patent ductus and mechanical ventilation (n = 17); PDA, with patent ductus (n = 6); MV, with mechanical ventilation (n = 9). The groups PDA+MV and MV had significantly lower creatinine clearances and significantly higher fractional sodium excretions than controls. Mean arterial pressure was significantly lower in all groups compared to controls and correlated significantly with creatinine clearance (r = 0.47, p < 0.02). In conclusion, low renal function in these infants is further compromised by a patent ductus arteriosus and/or the use of mechanical ventilation.

Creatinine↗
PubMed1993

Additional water is not needed for healthy breast-fed babies in a hot climate.

In Lahore, Pakistan, a community-based study was conducted to investigate whether or not it was necessary to give water to breast-fed infants. From May to November 1986, 2-4-month-old, breast-fed infants (n = 26) were selected. During the study period the maximum temperature ranged between 27.4 and 40.7 degrees C and humidity varied between 24 and 77%. Each infant was followed up for 15 days. Water was not allowed from day 1 to day 8 and water was allowed ad libitum from day 8 to day 15. All infants were subjected to a DDAVP test to estimate the renal concentrating capacity on day 15. A significant gain in weight (p < 0.001) was observed between day 1 to 8 and 8 to 15. The differences in the values of haematocrit and serum sodium between day 8 and 1 and between day 15 and 8 were not significant. This indicates that the infants were not dehydrated when water was withheld. Furthermore, no significant difference was observed for urine specific gravity between day 8 and 1, but urine specific gravity increased significantly after the administration of DDAVP (p < 0.001), indicating that, if needed, the infants could concentrate urine when water was restricted. It was concluded that 2-4-month-old, breast-fed, healthy infants showed no signs of dehydration if additional water was not given during the summer season.

Body Weight↗
PubMed1993

High salt alone does not influence the kinetics of the Na(+)-H+ antiporter.

During a high-salt diet, tubular sodium reabsorption is decreased. This study concerns the effect of a high-salt diet on the proximal tubular (PT) Na+ influx pathways. Brush-border membrane vesicles (BBMV) were prepared from rats on normal-salt (NS) and rats on high-salt (HS) diets. The initial uptake rates of Na+ were the same in NS and HS rats, both in the absence and the presence of 1 mM amiloride. Vmax and Km for the amiloride-sensitive Na+/H+ antiporter were also the same in the NS (Vmax 3.69 +/- 0.31 nmol mg prot-1 10 s-1, Km 6.13 +/- 0.58 mM) and HS groups (Vmax 3.54 +/- 0.28 nmol mg prot-1 10 s-1, Km 6.18 +/- 0.64 mM). There was no difference in the initial uptake rates of the Na(+)-glucose and the Na(+)-alanine symporters in NS and HS. Vmax and Km for the L-dopa-Na+ symporter were also the same in NS (Vmax 72 +/- 2.5 pmol mg prot-1 20 s-1, Km 98 +/- 14 microM) and HS groups (Vmax 78 +/- 6.0 pmol mg prot-1 20 s-1, Km 106 +/- 4 microM). In summary, HS diet does not change the kinetics of the Na+ transporters in the brush-border membrane of PT cells.

Amiloride↗