Effect of albumin concentration on albumin synthesis in the perfused liver

Rothschild, Marcus A.; Oratz, Murray; Mongelli, Joseph; Schreiber, S. S.

doi:10.1152/ajplegacy.1969.216.5.1127

Cited by 46 publications

(14 citation statements)

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“…The interplay of these vasoactive peptides on a systemic basis may, therefore, influence the metabolic function of specific organs, as recently suggested for volume regulatory responses modulating hepatic ammonia metabolism (44). However, since an inhibitory effect on albumin synthesis by colloids has also been described in ex vivo systems (16)(17)(18) (47)(48)(49). Studies are now in progress to identify specific 5' upstream sequences in the albumin gene that confer the regulatory response to this novel feedback regulatory mechanism.…”

Section: Discussionmentioning

confidence: 92%

“…An attractive possibility, supported by our data, is that the specific modulatory signal is mediated by changes in the COP that result from fluctuations in the serum or plasma level of albumin or other colloids. As originally proposed by Rothschild et al (16), such a colloid-mediated regulatory mechanism is presumably localized within the liver, perhaps in the interstitial space (i.e., space ofDisse) (34). However, in this region ofthe liver, the effective COP is thought to be low (35), and the actual concentrations of colloids in Disse's space may not reflect their concentration in the circulation.…”

Section: Discussionmentioning

confidence: 94%

“…In the 1960's, Rothschild et al (16) demonstrated that addition of albumin to the perfusate medium ofthe isolated rabbit liver decreases incorporation of labeled amino acids into albumin. Other studies extended this observation to macromolecules other than albumin, and it was proposed that all these agents may work through a common feedback mechanism based on their ability to influence the COP (17,18).…”

Section: Introductionmentioning

confidence: 99%

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Albumin gene expression is down-regulated by albumin or macromolecule infusion in the rat.

Pietrangelo¹,

Panduro²,

Chowdhury³

et al. 1992

J. Clin. Invest.

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IntroductionA novel feedback regulatory mechanism operating on transcription of the albumin gene is described in the rat. In 1946, it was proposed that circulating colloids, including serum albumin, may affect the synthesis and/or secretion ofalbumin in the liver. The molecular basis for this proposed regulation has now been investigated by adding oncotically active macromolecules to the circulation of normal or genetically albumin-deficient Nagase analbuminemic rats (NAR) and analyzing the hepatic expression of genes, including albumin after 24 h. The transcription rate of the albumin gene was higher in NAR than in normal rats and was dramatically reduced by raising serum albumin to 1.6 g/dl. Intravenous infusion of albumin into normal rats also decreased transcriptional activity of the albumin gene by 50-60%, and this decrease correlated with changes in serum colloid osmotic pressure after albumin infusion. Inhibition ofalbumin gene transcription was also observed upon intravenous infusion of other protein or nonprotein macromolecules, such as y-globulin and dextran. This down-regulation appears to control the steady-state level of albumin mRNA in the liver.Aside from a concomitant decrease in apo E gene transcription after albumin or macromolecule infusion, there was no change in the transcription rate of other genes, including those exhibiting liver-preferred or -specific expression (e.g., tyrosine aminotransferase, cytochrome P450, a1-antitrypsin, apolipoproteins A-I and B, and transferrin) or general cellular expression (e.g., a-tubulin, pro a2 collagen, and fl-actin). The liver represents the main source of serum albumin (1, 2). Normally, the plasma albumin concentration remains constant at 3.5-4.0 g/dl, suggesting an active regulation ofalbumin metabolism. Several pathophysiological studies have shown that hormones, malnutrition, and stress may influence albumin synthesis (3-7); however, little is known about the "physiological" regulator(s) of albumin or other proteins synthesized by the liver. Many years ago, Biorneboe (8, 9) observed that an increase in the serum concentration ofglobulins is followed by a concomitant decrease ofserum albumin in hepatitis and after immunization, and he proposed that the serum colloid osmotic pressure (COP)' might serve as a regulator for changes in serum protein concentration. In support ofthis hypothesis, hyperglobulinemia, infusion of y-globulin, and administration of dextran were also shown to decrease serum albumin levels (10-12). Moreover, in a variety ofconditions in which serum albumin levels fall either acutely (e.g., plasmapheresis) or chronically (e.g., nephrotic syndrome), hepatic albumin synthesis is increased (13)(14)(15).In the 1960's, Rothschild et al. (16) demonstrated that addition of albumin to the perfusate medium ofthe isolated rabbit liver decreases incorporation of labeled amino acids into albumin. Other studies extended this observation to macromolecules other than albumin, and it was proposed that all these agents may work through a com...

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Albumin gene expression is down-regulated by albumin or macromolecule infusion in the rat.

Pietrangelo¹,

Panduro²,

Chowdhury³

et al. 1992

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…2 hr after CC14 ingestion, the rabbits were anesthetized with open drop ether and the livers removed and mounted in a humidified chamber for perfusion as previously described (12)(13)(14)(15). During surgery, the liver was perfused by an auxilliary perfusion and was deprived of brood for less than 15 sec.…”

Section: Methodsmentioning

confidence: 99%

“…The space of distribution of urea in the liver and red cell has been determined to average 60%. Urea-"C activity was determined at the end of the perfusion and related to the net urea synthesis (15). The specific activity of this urea carbon was assumed to equal the mean specific activity of the precursor guanido carbon of arginine (16)(17)(18).…”

Section: Methodsmentioning

confidence: 99%