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Biomedical subjects

F A Carone

Publications and source records attributed to F A Carone.

At least 73 records · Page 4Linked to original sources
PubMed1984

Renal handling of plasma high density lipoprotein.

Renal tubular reabsorption and hydrolysis of plasma high density lipoprotein (HDL3) were studied. Rabbit proximal straight nephron segments were microperfused in vitro with iodinated HDL3. Progressive luminal uptake and cellular accumulation of radiolabeled material were observed during an initial phase, followed by a reduction in sequestration and the appearance of 125I-label in the bathing medium. To detect proteolysis, collected perfusates and bathing media were analyzed for trichloracetic acid soluble radioactivity. 125I-HDL3 in the luminal fluid was intact, but metabolites appeared in the bathing medium. Electron microscopic radioautography demonstrated endocytic uptake of 125I-HDL3 at the luminal membrane of the proximal tubule and movement of grains into lysosome-like dense bodies. Incubation of radiolabeled HDL3 in the presence of renal homogenates resulted in proteolytic activity with an acidic pH optimum. Analytical cell fractionation studies indicated that hydrolysis of the protein component is associated with lysosomes derived from proximal kidney tubules. Collectively, the data show that plasma HDL3 can be reabsorbed in the proximal nephron by a mechanism involving endocytosis at the luminal membrane, followed by proteolysis at lysosomes.

Absorption↗
PubMed1983

Renal tubular uptake of protein: effect of molecular charge.

The effect of molecular charge of proteins on proximal tubular reabsorption was evaluated in the rat. Native and two cationized forms of albumin, native and anionized lysozyme, and native and anionized cytochrome c were iodinated with 125I. The different forms of each type of protein were alternately microinfused into the same site of proximal convoluted tubules in vivo. Tubular reabsorption was determined as the difference between the amounts of TCA-precipitable radioactivity infused and recovered in the urine. At low concentration of albumin 5 times more cationized than anionic albumin and 2.7 times more cationic than anionized lysozyme were reabsorbed by the proximal tubule. At two of four concentrations, proximal tubular uptake of cationic cytochrome c exceeded that of anionized cytochrome c. Uptake of cationic cytochrome c exceeded that of cationic lysozyme; however, the difference in uptake between native cationic and anionized species of the two proteins was much greater for lysozyme than for cytochrome c. The data reveal that a higher isoelectric point significantly enhances proximal tubular reabsorption of albumin, lysozyme, and cytochrome c and that proteins with similar molecular weight and isoelectric point are not necessarily reabsorbed to the same degree. This suggests that in addition to total molecular charge the molecular configuration and/or distribution of electrical charges on teh protein surface determine protein binding by the luminal membrane and subsequent endocytosis by the proximal tubule.

Animals↗
PubMed1983

In vivo metabolism of tritiated LHRH by the whole kidney and individual tubules of rats.

[pyroglutamyl-3,4-3H]Luteinizing hormone-releasing hormone ([3H]LHRH) and [14C]inulin were infused into individual nephrons in Inactin-anesthetized rats and the amount of radioactive label and the identity of the radioactively labeled material in urine were determined. The site of infusion was identified by latex injection and microdissection. [3H]LHRH was microinfused at 1.5 X 10(-5 M (concentration 10(6)-10(7) higher than in plasma) and analysis of urinary metabolites was performed by high-performance liquid chromatography. The urinary recovery of tritium label was 81% when proximal tubules were infused and 94% when distal tubules were infused. For proximal tubules 90% of the label recovered in urine appeared as pGlu-His (metabolite 2), pGlu-His-Trp (metabolite 3), and pGlu-His-Trp-Ser (metabolite 4), and 10% as LHRH. With distal tubules only LHRH was detected in the urine. [3H]LHRH was presented to the renal artery of the filtering rat kidney in vivo, and urine and renal venous blood were analyzed for breakdown products. The urine contained metabolites 2, 3, and 4 and no LHRH, whereas venous blood contained mainly pGlu, metabolite 4, and LHRH. When [3H]LHRH was perfused in vivo through the nonfiltering rat kidney or rat lower limb, renal or femoral venous blood was found to contain only LHRH. These studies suggest that [3H]LHRH undergoes glomerular filtration and contact digestion by brush border enzymes of the proximal tubule to produce metabolites 2, 3, and 4. These metabolites and possibly LHRH are partially reabsorbed and undergo further intracellular degradation to produce pGlu. Endothelial and interstitial cells in the kidney and leg do not appreciably metabolize [3H]LHRH.

Animals↗
PubMed1983

Acute hemorrhagic obstructive uropathy as a complication of experimental autoimmune encephalomyelitis.

During studies related to immunoregulation in experimental allergic encephalomyelitis (EAE) in rats, acute hemorrhagic obstructive uropathy developed as an unexpected complication. The urinary retention was attributed to mucous plugs tightly impacted into the bladder neck. Although mucous plugs commonly are detected in the bladders of healthy adult rats, they could create a serious complication when impacted into the outflow tract as the result of malfunctioning sphincter actions by EAE-induced spinal cord injury.

Acute Disease↗
PubMed1982

Differences between renal tubular processing of glucagon and insulin.

Renal processing of glucagon and insulin was compared. Iodinated glucagon (mol wt 3,674, linear molecule) or insulin (mol wt 6,000, two chains with disulfide bonds) was microinfused into surface nephrons of the rat kidney, and the radiolabel recovered in the urine was quantified and characterized. Proximal but not distal reabsorption of both peptides was observed, and uptake varied similarly as a function of tubular length. After proximal microinfusion, [125I]glucagon was largely degraded to [125I]tyrosine in the urine, but remained intact after distal infusion. [125I]Insulin was recovered as intact peptide following both proximal and distal microinfusion. Prolonged tubular sequestration of 125I label was observed following proximal microinfusion of [125I]insulin, with efflux requiring longer than 1 h for completion. No measurable cellular sequestration of [125I]glucagon was observed. Incubation of both peptides with rabbit renal microvilli membranes resulted in enzymatic hydrolysis of [125I]glucagon but relatively little or no degradation of [125I]insulin. It is concluded that glucagon and insulin are reabsorbed in the proximal tubule by predominantly different mechanisms.

Absorption↗
PubMed1982

Renal tubular processing of small peptide hormones.

Reabsorption and/or degradation of proteins or peptides are functions of the proximal tubule. Large polypeptides or proteins are reabsorbed by luminal endocytosis and hydrolyzed by lysosomal enzymes. Our recent studies indicate that small linear peptides are hydrolyzed at the luminal membrane, with reabsorption of metabolites. The renal transport and hydrolysis of radiolabeled Al, All, BKN, oxytocin, glucagon, insulin, and LHRH were studied. Techniques for in vivo microinfusion of surface tubules in rats, arterial infusion in filtering and nonfiltering rat kidneys in vivo, and in vitro microperfusion of isolated rabbit nephron segments were used. Reabsorption of radiolabeled material was measured and the intact peptide or its metabolites were identified and quantified in urine, renal venous blood, bathing medium, and/or collection fluid. In addition, peptides were incubated in the presence of isolated renal membrane preparations to identify a probably cellular site of hydrolysis. The findings indicate that in proximal, but not distal tubules, radiolabeled Al, All, BKN, glucagon, and LHRH are hydrolyzed by brush border enzymes at the luminal membrane, followed by reabsorption of metabolites. In addition, it was found that, similar to the small intestine, the proximal tubule reabsorbed small peptide fragments, which were further degraded intracellurarly, In vivo inhibition studies with excess peptides revealed that hydrolysis is a more specific process than studies with excess peptides revealed that hydrolysis is a more specific process than reabsorption of metabolites. Large or small, complex peptides like insulin, oxytocin, or vasopressin that contain disulfide bridges are not hydrolyzed at the luminal brush border of the proximal tubule. In vivo sequestration and slow degradation of insulin by rat tubules suggest that this peptide is reabsorbed by endocytosis and degraded in lysosomes. Thus, as the molecular complexity or weight of a peptide increases, the mechanism for renal tubular degradation, instead of depending on luminal membrane hydrolysis, may primarily involve endocytosis and lysosomal digestion. This recently described mechanism for hydrolysis and transport of small linear peptides in the proximal nephron is characterized by having a high capacity and is analogous to membrane hydrolysis described for intestinal microvilli. The process may be biologically important to (1) conserve amino acids, (2) inactivate toxic peptides, and (3) help regulate circulating levels of peptide hormones.

Angiotensin I↗
PubMed1979

Renal regeneration following d-serine induced acute tubular necrosis.

Regeneration of the ray kidney was observed for six days after inducing acute tubular necrosis of the proximal pars recta with d-serine (80 mg/100 g body weight. Regenerating cells appear by two days post-treatment, and re-epithelialization of the nephron is completed within six days, with the most mature cells approaching normal morphology. Regeneration originates from viable cells adjacent to the necrotic zone which divide and follow a template provided by the intact basement membrane. Transient, cytoplasmic regenerative activity among developing tubular cells is characterized by the presence of large, irregularly shaped nuclei, prominent nucleoli, abundant ribosomes and lysosomes, and abnormal mitochondrial configurations. Microfilaments appear to be involved in the formation of apical microvilli and the basal labyrinth of plasmalemmal convolutions. These data suggest that d-serine induced acute tubular necrosis of the proximal pars recta may be followed by rapid, patterned regeneration along an intact basement membrane, and that microfilaments are involved in differentiation of cellular morphology.

Acute Kidney Injury↗
PubMed1979

The treatment of the hemolytic-uremic syndrome with inhibitors of platelet function.

In four patients with clinical and laboratory manifestations of the hemolytic-uremic syndrome, the administration of aspirin and dipyridamole was associated with a dramatic and rapid increase in the platelet count. In three of the four patients there was also improvement in neurologic or renal function. No subject experienced bleeding or other untoward effects. We conclude that a trial of aspirin and dipyridamole therapy is warranted early in the course of the hemolytic-uremic syndrome.

Adult↗
PubMed1979

Renal tubular transport and catabolism of proteins and peptides.

The kidney plays an important role in the metabolism of proteins and peptides. Current evidence indicates that only the proximal tubule possesses the mechanism for degradation or transport of these substances and reabsorption of metabolic products. Proteins and large polypeptides filtered at the glomerulus are absorbed from proximal tubular fluid by luminal endocytosis into apical vacuoles. These fuse with primary lysosomes, where hydrolysis occurs followed by diffusion of metabolites out of the cells and into the blood. Recent evidence indicates that small linear peptides are handled by a different mechanism. It is likely that small peptides are degraded at the luminal surface of the brush border of proximal tubules, which contains many hydrolytic enzymes, by the process of membrane or contact digestion with reabsorption of the breakdown products. The probable biological significance of proximal tubular mechanisms for handling of proteins and peptides are conservation of amino acids, inactivation of toxic substances, and participation in the regulation of the circulating level of protein and peptide hormones.

Animals↗