Erythropoietin in liver tissue extracts and in liver perfusates from hypoxic rats

Caro, Jaime; Zon, Leonard I.; Silver, Ruth; Miller, Orin P.; Erslev, Allan J.

doi:10.1152/ajpendo.1983.244.5.e431

Cited by 8 publications

(4 citation statements)

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“…In CRF, the adaptation of EPO levels to Hb concentration is lost, EPO production is seriously disturbed and its levels are much lower than those observed in non-renal anaemias of Assessment of Erythropoietin Levels and Some Iron Indices in Chronic Renal Failure and Liver Cirrhosis Patients comparable severity. Hepatically produced EPO is evidently of no compensatory value [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Erythropoietin Levels and Some Iron Indices in Chronic Renal Failure and Liver Cirrhosis Patients

Mady

Wissa²,

Khalifa³

et al. 1999

Disease Markers

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This study was constructed to investigate the relationship between renal anaemia and erythropoietin (EPO) concentrations in chronic renal failure (CRF) patients and to evaluate the possible role of the liver. Serum EPO levels were measured in blood samples from 20 CRF patients on hemodialysis (HD), 20 liver cirrhosis (LC) patients, 20 patients having both CRF and LC and undergoing HD, and 20 normal control subjects. Blood cell counts, iron indices (iron, total iron-binding capacity (TIBC) and ferritin), renal function (blood urea nitrogen (BUN) and creatinine), hepatic function (ALT, AST, ALP and bilirubin) investigations were carried out for all the subjects enrolled in this study. CRF patients without LC had serum EPO concentration of 6.21 ± 0.53 mU/ml (mean ± SE), which was significantly higher than that in patients having both CRF and LC (4.32 ± 0.52) (p < 0.01). Both groups showed significantly lower values than the controls (12.75 ± 0.70) (p < 0.001). LC patients with intact kidneys had significantly higher EPO level (22.70 ± 1.70) (p < 0.001). No correlation was found between EPO level and any of the hematologic or iron indices.

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Section: Introductionmentioning

confidence: 99%

Assessment of Erythropoietin Levels and Some Iron Indices in Chronic Renal Failure and Liver Cirrhosis Patients

Mady

Wissa²,

Khalifa³

et al. 1999

Disease Markers

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“…In hypoxic animals, EP can be extracted from renal tissues but not other tissues (2, 3). The only other organ which has been implicated in EP production is the liver of fetal (14) or nephrectomized (1,3,8) animals. The recent cloning of the mouse EP gene (12) provides the probes necessary for analysis of the organ distribution, quantitation, and time course of accumulation of EP-specific mRNA transcripts in mice made hypoxic by blood loss.…”

mentioning

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Anemia induces accumulation of erythropoietin mRNA in the kidney and liver.

Bondurant¹,

Koury²

1986

Mol. Cell. Biol.

222

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Regulation of the production of erythropoietin occurs in the kidney and liver largely through control of accumulation of erythropoietin mRNA. Erythropoietin mRNA was first detected in kidneys at 1.5 h postanemia and reached a plateau value at least 200-fold above the control value by 4 to 8 h. A 20-base sequence immediately upstream from the reported erythropoietin mRNA initiation site is complementary to a hypervariable sequence in 18S rRNA.Erythropoietin (EP) is a glycoprotein hormone which is the principal regulator of mammalian erythrocyte development. Studies measuring the biological activity of EP have demonstrated that the kidney plays a predominant role in raising circulating EP titers in response to hypoxia (6, 7). In hypoxic animals, EP can be extracted from renal tissues but not other tissues (2, 3). The only other organ which has been implicated in EP production is the liver of fetal (14) or nephrectomized (1,3,8) animals. The recent cloning of the mouse EP gene (12) provides the probes necessary for analysis of the organ distribution, quantitation, and time course of accumulation of EP-specific mRNA transcripts in mice made hypoxic by blood loss.RNA was isolated from mouse organs by homogenizing them in guanidine isothiocyanate and sedimenting the RNA through 5.7 M CsCl (4). Polyadenylated RNA was isolated by chromatography with oligo(dT)-cellulose. For electrophoresis, 6 to 25 ,ug of polyadenylated RNA or 30 to 50 ,ug of total cellular RNA was loaded per lane on formaldehyde-1.5% agarose gels (9). After electrophoresis, the gels were blotted onto nitrocellulose sheets and hybridized by the method of Thomas (13), except that no dextran sulfate was added to the hybridization buffer. DNA probes were labeled by nick translation (11) to a specific activity of 108 cpm/,Lg of DNA. Figure 1 depicts the structure of the mouse EP gene. Plasmid DB2-5, which has the indicated 4.5-kilobase-pair BglII fragment of the mouse EP gene inserted into the BainHI site of the plasmid vector pUC19 (12), was a gift from C. Shoemaker, Genetics Institute, Cambridge, Mass. The inserted BglII fragment contains the entire promoter and coding regions of the gene (and most of the 3' untranslated sequence). The probe used to detect EP-specific transcripts was the BamHI-EcoRI fragment or the BamHI-SmaI fragment prepared from DB2-5 by digestion and isolation from a 1% agarose gel (Fig. 1). The forme' probe is more sensitive than the latter, but in addition to EP mRNA it also hybridizes with a small nucleic acid species, present in equal amounts in all mouse cells, which migrates diffusely with the dye front in formaldehyde-agarose gels.For studies of the organ distribution of EP mRNA, female BALB/c mice aged 12 to 14 weeks and weighing 20 to 24 g were made anemic by bleeding from the retroorbital sinus. The mice were bled 0.4 ml at 36, 24, and 16 h before * Corresponding author.sacrificed by cervical dislocation. Their hematocrits just before sacrifice were 17 to 20%, whereas hematocrits of normal animals were 48 to 51%. The results...

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“…In the Erslev lab, Zon dissected rat livers in search of erythropoietin, hoping to shed light on how the hormone was made and could be produced for medical use. He concluded that the livers contained low amounts of erythropoietin ( 4 ), but his fascination surrounding blood cells and anemia endured. Erslev advised Zon to continue training in hematology at Harvard University.…”

Section: Hooked By a Lecturementioning

confidence: 99%

Profile of Leonard I. Zon

Williams¹

2023

Proc. Natl. Acad. Sci. U.S.A.

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Erythropoietin in liver tissue extracts and in liver perfusates from hypoxic rats

Cited by 8 publications

References 4 publications

Assessment of Erythropoietin Levels and Some Iron Indices in Chronic Renal Failure and Liver Cirrhosis Patients

Assessment of Erythropoietin Levels and Some Iron Indices in Chronic Renal Failure and Liver Cirrhosis Patients

Anemia induces accumulation of erythropoietin mRNA in the kidney and liver.

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