Renal erythropoietin: Properties and production

Jelkmann, Wolfgang

doi:10.1007/bfb0031014

Cited by 104 publications

(25 citation statements)

References 372 publications

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“…Though EPO was not measured in this study, we assume that the recurrent apnoeic episodes associated with underwater swimming provided a sufficient hypoxic signal to stimulate renal EPO synthesis in diveconditioned muskrats. It is well-established that this glycoprotein stimulates erythropoiesis by enhancing mitotic frequency and promoting iron uptake and Hb synthesis by erythroid-committed cells in bone marrow (Jelkmann, 1986;Kranz, 1991). Consequently, the observed gains in Hct, Hb and blood oxygen capacity of 'divers' probably reflect elevated EPO production by the kidneys of these animals.…”

Section: Dive Conditioning and Body Oxygen Reservesmentioning

confidence: 99%

Diving experience and the aerobic dive capacity of muskrats: does training produce a better diver?

MacArthur

Weseen

Campbell

2003

Journal of Experimental Biology

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SUMMARY We tested the hypothesis that the body oxygen stores, aerobic dive limit(ADL) and dive performance of muskrats can be enhanced by dive-conditioning in a laboratory setting. We compared several key variables in 12 muskrats trained to swim a 16 m underwater course to a feeding station (`divers') with those of 12 animals precluded from diving but required to travel identical distances in water to feed (`surface swimmers'). Acclimated muskrats assigned to each group were trained concurrently over a 9–11 week period. We observed significant gains in the haematocrit (P=0.0005) and blood haemoglobin concentration (P=0.015) of `divers', but not `surface swimmers'. The post-training blood O2 store calculated for `divers' (22.9 ml O2 kg–1) was nearly 26% higher than that (18.2 ml O2 kg–1) derived for `surface swimmers'(P=0.03). Dive-conditioning had no apparent effect on lung volume,whole blood and plasma volumes, nor on the glycogen level and buffering capacity of skeletal muscles. Cardiac and skeletal muscle myoglobin levels were also similar in both test groups following training. The mean total body oxygen store of `divers' (37.8ml O2 STPD kg–1) was 13.5% higher (P=0.037) than for `surface swimmers' (33.3 ml O2 STPD kg–1), an increase attributed entirely to the gain in blood O2 storage capacity of the former group. However,owing to a slightly higher estimate of diving metabolic rate in dive-conditioned animals, the calculated ADL for this group (61.3 s) was indistinguishable from that of `surface swimmers' (61.8 s). Few differences were observed in the post-training dive behaviour of `surface swimmers' and`divers', a finding consistent with the strong similarity in their calculated aerobic dive capacities.

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Section: Dive Conditioning and Body Oxygen Reservesmentioning

confidence: 99%

Diving experience and the aerobic dive capacity of muskrats: does training produce a better diver?

MacArthur

Weseen

Campbell

2003

Journal of Experimental Biology

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“…This nonlabile, Amadori product of glucose and Hb has been shown to provide an integrated assessment of mean glucose concentration during the preceding four to six weeks [7]. Plasma Ep concentration was selected as the indicator of fetal oxygenation since Ep production in both the fetus and the adult is primarily mediated through fluctuations in tissue oxygenation [18]. Furthermore, since maternal Ep does not cross the placenta [8], fetal Ep concentration reflects fetal oxygenation.…”

Section: Statistical Pathway Modelmentioning

confidence: 99%

Direct relationship of antepartum glucose control and fetal erythropoietin in human Type 1 (insulin-dependent) diabetic pregnancy

et al. 1990

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Summary. In the present study the antepartum relationship between maternal diabetic glucose control and fetal hypoxaemia was examined in 44 Type i (insulin-dependent) diabetic and 23 non-diabetic control pregnancies. Maternal HbAlc was used to assess maternal integrated blood glucose control while fetal metabolic control was evaluated by antepartum glucose, insulin, and C-peptide determinations in amniotic fluid at elective caesarean delivery. Fetal hypoxaemia was assessed indirectly by fetal umbilical vein plasma erythropoietin level at delivery. A prospectively developed statistical pathway model was used to examine the relationship of these variables. In applying forced stepwise multiple regression with this model, we observed in the diabetic subjects that mean maternal HbA~c during the last month of pregnancy correlated significantly with fetal umbilical venous erythropoietin at delivery (r = 0.57,p < 0.001). Additional significant contributions to umbilical venous erythropoietin were found for amniotic fluid glucose and amniotic fluid insulin when these two independent variables were added in stepwise fashion (p < 0.01). We conclude that in diabetic pregnancy, antepartum control of maternal hyperglycaemia is a significant factor associated with fetal hypoxaemia. We speculate that this effect is mediated through perturbations which accelerate fetal metabolism and which is expressed by amniotic fluid levels of glucose and insulin.Key words: Erythropoietin, HbAlc, fetus, oxygenation, diabetes mellitus.Although in recent years the outcome of diabetic pregnancies has dramatically improved, fetal and neonatal morbidity and mortality remain increased relative to normal pregnancies [1,2]. Some of the pathological features observed in offspring of these pregnancies have been shown to be associated with maternal hyperglycaemia (eg., respiratory distress syndrome, congenital malformations, and neonatal hypoglycaemia); others have not. Among the latter are the increased incidence of late gestation fetal death, antepartum and intrapartum fetal distress, and neonatal polycythaemia. We and others have speculated that these features of diabetic pregnancies have their origins in chronic and/or acute fetal hypoxaemia [3][4][5].The purpose of the present study was to indirectly examine the antepartum relationship between chronic maternal hyperglycaemia and fetal oxygenation in Type 1 (insulin-dependent) diabetic pregnancies delivered by elective caesarean section before the confounding effect of labour [6]. To do so, we prospectively developed a hypothetical pathway model for statistical analyses in which chronic maternal hyperglycaemia was related to chronic fetal hypoxaemia through several intermediate steps. Subjects and methods SubjectsAfter obtaining approval by the Ethical Committee at the University of Helsinki and after obtaining each patient's consent, control and Type i (insulin-dependent) diabetic subjects carrying singleton fetuses were studied at the Women's Hospital of the University Central Hospital of Helsink...

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“…Epo synthesis is regulated via feedback mechanisms involving tissue oxygen tension. Since the work of Jacobson et al (1), evidence has accumulated suggesting that the kidney is the major source of Epo production (2). However, the identity of the kidney cells that are responsible for Epo biosynthesis is still a matter ofcontroversy.…”

Section: Introductionmentioning

confidence: 99%

Peritubular cells are the site of erythropoietin synthesis in the murine hypoxic kidney.

Lacombe

Silva²,

Bruneval³

et al. 1988

J. Clin. Invest.

413

163

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Erythropoietin (Epo)-producing cells were identified in the murine hypoxic kidney by in situ hybridization. Profound anemia was induced in order to greatly increase Epo production. This resulted in high levels of Epo mRNA in the kidney. 35S-labeled DNA fragments of the murine Epo gene were used as probes for in situ hybridization. Control experiments conducted in parallel included kidneys of nonanemic mice, RNase-treated hypoxic kidney sections, and 35S-labeled nonEpo-related DNA. The Epo probe gave a specific hybridization signal in the hypoxic kidney in the cortex and to a lesser extent in the outer medulla. Glomerular and tubular cells were not labeled. All positive cells were identified as peritubular cells.Using immunofluorescence, we showed that cells with the same topography contained Factor VIII-related antigen. These data demonstrated that peritubular cells, most likely endothelial cells, constitute the major site of Epo production in the murine hypoxic kidney.

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Renal erythropoietin: Properties and production

Cited by 104 publications

References 372 publications

Diving experience and the aerobic dive capacity of muskrats: does training produce a better diver?

Diving experience and the aerobic dive capacity of muskrats: does training produce a better diver?

Direct relationship of antepartum glucose control and fetal erythropoietin in human Type 1 (insulin-dependent) diabetic pregnancy

Peritubular cells are the site of erythropoietin synthesis in the murine hypoxic kidney.

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