Abstract
The hepatic synthesis of several proteins, including both albumin and transferrin is increased in the nephrotic syndrome. While active suppression of albumin synthesis by lymphokines has been described, it has been assumed that augmentation of albumin synthesis is governed by a physical factor, plasma oncotic pressure (π), and that this regulation is by a direct effect of π on hepatocytes. The mechanisms have not been defined. Furthermore, experiments relying on suppression of protein synthesis may only test non-specific inhibitory effects of the experimental intervention. We tested an alternative hypothesis that a serum factor(s) present in hypooncotic states stimulates albumin synthesis. We incubated an immortalized cell line derived from rat hepatocytes (H4 cells) with serum from Nagase analbuminemic rats (NAR) and rats with passive Heymann nephritis (HN), a model of the nephrotic syndrome. Synthesis (incorporation of [35S]methionine) into both albumin and transferrin was increased significantly. The stimulatory effect of these sera was not extinguished by addition of rat or human albumin to the medium prior to or during incubation, even when π in the incubation medium was increased to normal plasma levels by added albumin. Incorporation of [35S]methionine into albumin was 7841 ± 394 cpm/mg cell protein using 10% NAR serum in the presence of human albumin (medium π 26.1 ± 0.17) versus 5149 ± 420 cpm incorporation (P < 0.05) in the presence of control serum and in the absence of added albumin (medium π 2.06 ± 0.26 mm Hg, P < 0.001). The stimulatory activity was preserved following heating of serum for one hour at 60°C. These observations suggest that albumin and transferrin synthesis is stimulated by a heat stable factor found in serum when plasma π is reduced, rather than as a consequence of the interaction of π directly with the hepatocyte.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1381-1387 |
| Number of pages | 7 |
| Journal | Kidney International |
| Volume | 45 |
| Issue number | 5 |
| State | Published - May 1994 |
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ASJC Scopus subject areas
- Nephrology
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Albumin and transferrin synthesis are increased in H4 cells by serum from analbuminemic or nephrotic rats. / Sun, Xihua; Kaysen, George.
In: Kidney International, Vol. 45, No. 5, 05.1994, p. 1381-1387.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Albumin and transferrin synthesis are increased in H4 cells by serum from analbuminemic or nephrotic rats
AU - Sun, Xihua
AU - Kaysen, George
PY - 1994/5
Y1 - 1994/5
N2 - The hepatic synthesis of several proteins, including both albumin and transferrin is increased in the nephrotic syndrome. While active suppression of albumin synthesis by lymphokines has been described, it has been assumed that augmentation of albumin synthesis is governed by a physical factor, plasma oncotic pressure (π), and that this regulation is by a direct effect of π on hepatocytes. The mechanisms have not been defined. Furthermore, experiments relying on suppression of protein synthesis may only test non-specific inhibitory effects of the experimental intervention. We tested an alternative hypothesis that a serum factor(s) present in hypooncotic states stimulates albumin synthesis. We incubated an immortalized cell line derived from rat hepatocytes (H4 cells) with serum from Nagase analbuminemic rats (NAR) and rats with passive Heymann nephritis (HN), a model of the nephrotic syndrome. Synthesis (incorporation of [35S]methionine) into both albumin and transferrin was increased significantly. The stimulatory effect of these sera was not extinguished by addition of rat or human albumin to the medium prior to or during incubation, even when π in the incubation medium was increased to normal plasma levels by added albumin. Incorporation of [35S]methionine into albumin was 7841 ± 394 cpm/mg cell protein using 10% NAR serum in the presence of human albumin (medium π 26.1 ± 0.17) versus 5149 ± 420 cpm incorporation (P < 0.05) in the presence of control serum and in the absence of added albumin (medium π 2.06 ± 0.26 mm Hg, P < 0.001). The stimulatory activity was preserved following heating of serum for one hour at 60°C. These observations suggest that albumin and transferrin synthesis is stimulated by a heat stable factor found in serum when plasma π is reduced, rather than as a consequence of the interaction of π directly with the hepatocyte.
AB - The hepatic synthesis of several proteins, including both albumin and transferrin is increased in the nephrotic syndrome. While active suppression of albumin synthesis by lymphokines has been described, it has been assumed that augmentation of albumin synthesis is governed by a physical factor, plasma oncotic pressure (π), and that this regulation is by a direct effect of π on hepatocytes. The mechanisms have not been defined. Furthermore, experiments relying on suppression of protein synthesis may only test non-specific inhibitory effects of the experimental intervention. We tested an alternative hypothesis that a serum factor(s) present in hypooncotic states stimulates albumin synthesis. We incubated an immortalized cell line derived from rat hepatocytes (H4 cells) with serum from Nagase analbuminemic rats (NAR) and rats with passive Heymann nephritis (HN), a model of the nephrotic syndrome. Synthesis (incorporation of [35S]methionine) into both albumin and transferrin was increased significantly. The stimulatory effect of these sera was not extinguished by addition of rat or human albumin to the medium prior to or during incubation, even when π in the incubation medium was increased to normal plasma levels by added albumin. Incorporation of [35S]methionine into albumin was 7841 ± 394 cpm/mg cell protein using 10% NAR serum in the presence of human albumin (medium π 26.1 ± 0.17) versus 5149 ± 420 cpm incorporation (P < 0.05) in the presence of control serum and in the absence of added albumin (medium π 2.06 ± 0.26 mm Hg, P < 0.001). The stimulatory activity was preserved following heating of serum for one hour at 60°C. These observations suggest that albumin and transferrin synthesis is stimulated by a heat stable factor found in serum when plasma π is reduced, rather than as a consequence of the interaction of π directly with the hepatocyte.
UR - http://www.scopus.com/inward/record.url?scp=0028354449&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028354449&partnerID=8YFLogxK
M3 - Article
C2 - 7520954
AN - SCOPUS:0028354449
VL - 45
SP - 1381
EP - 1387
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 5
ER -