Purification of a liver DNA-synthesis promoter from plasma of partially hepatectomized rats

Abstract

A protein was isolated from plasma of partially (70%) hepatectomized rats that, injected in mice, increases the uptake of [3H]thymidine by liver DNA by 200-300% over that by injected control saline. The purification procedure consists essentially of three chromatography steps, employing Sephadex G-75, DEAE-cellulose and hydroxyapatite. The hepatic promoter (HP) preparation shows a single band in SDS/polyacrylamide (15%)-gel electrophoresis (silver stained), with an Mr of 64 000; its activity is suppressed by trypsin or pepsin and is unaffected by deoxyribonuclease or ribonuclease. On injection into mice (150 ng/mouse), it increases the mitotic index of the liver. It shows organ-specificity, acting on liver but not on spleen, kidney, lung or brain. In primary liver cultures, it produces an increase in uptake of [3H]thymidine into DNA in the range 1-10 ng/ml. In this system in vitro, it increases the uptake of 22Na+ immediately after addition.

The role of transferrin in the mechanism of cellular iron uptake

“…Furthermore, growth inhibitors such as adriamycin, bleomycin and retinoic acid are also inhibitors of the redox system [91][92][93], and cell growth promoters also stimulate the NADH: ferricyanide oxidoreductase [94,95]. Finally, transferrin stimulates the redox system and induces proton efflux via the Na+/H+ antiport [40,41,96], whereas some antibodies against the transferrin receptor inhibit the redox system [97].…”

Liver growth factor treatment restores cell-extracellular matrix balance in resistance arteries and improves left ventricular hypertrophy in SHR

“…The effective cardiovascular antifibrotic and regenerative actions of LGF support its potential in the treatment of hypertension and its complications. intramyocardial arteries; mesenteric resistance arteries; nitric oxide; vascular remodeling; left ventricular hypertrophy LIVER GROWTH FACTOR (LGF) was first described as an endogenous factor with mitogenic properties in liver (21).LGF is not detected in physiological conditions, but it increases in plasma in situations of hepato-biliary disorders, both in humans and rats (21,24). The chemical analysis of LGF obtained from human and rat plasma has revealed that it is a covalently bound albumin-bilirubin complex (24,25).…”

A liver DNA synthesis promoter induced in rat plasma by injection of dimethylnitrosamine (DMNA) or thioacetamide

“…The possible importance of HP in hepatic regeneration has been reinforced by the recent publication by our group of a similar activity, present in plasma of humans with acute viral hepatitis (Diaz Gil et al, 1986b …”

“…Heparinized blood was collected by cardiac puncture and plasma was obtained after centrifugation. The HP was purified from plasma in every case, whether from DMNA or thioacetamide-injected, normal or partially hepatectomized rats, using the isolation procedure published by our group (Diaz-Gil et al, 1986a). In brief, it consists of three main chromatographic steps: Sephadex G-75, DEAE-cellulose and hydroxylapatite.…”

“…Our group has recently reported (Diaz-Gil et al, 1986a) the purification of a liver DNA synthesis promoter (HP) from plasma of partially hepatectomized rats. The HP preparation shows a single band on SDS-polyacrylamide gel electrophoresis (silver-stained), with a molecular weight of 64,000, and appears to be a protein.…”