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W Jelkmann

Publications and source records attributed to W Jelkmann.

At least 145 records · Page 8Linked to original sources
PubMed1983

Effects of fasting on the hypoxia-induced erythropoietin production in rats.

In order to test the hypothesis that the early cessation of erythropoietin (Ep) production during hypobaric hypoxia is induced by lowered food intake, we have compared the plasma Ep titer of rats after exposure to continuous hypoxia (42.6 kPa = 7000 m altitude) for 4 days with that in fed or fasted rats after exposure to discontinuous hypoxia. We found that plasma Ep was rather low after 4 days of continuous hypoxia. However, the Ep titer significantly rose again, when rats were maintained normoxic for 18 h and then exposed to repeated hypoxia for 6 h. Because this was also found in rats which were deprived of food during the normoxic interval and the second hypoxic period, we conclude that the fall of the Ep titer during continuous hypoxia is not primarily due to reduced food intake. In addition, our findings show that fasting per se lowers the Ep-response to hypoxia in normal rats but not exhypoxic rats.

Animals↗
PubMed1983

Renal mesangial cell cultures as a model for study of erythropoietin production.

Mesangial cells derived from isolated glomeruli of rat kidney were grown as homogeneous cell lines in culture. They released, into the culture medium, erythropoietin that had free terminal galactosyl residues and was therefore not active in vivo. The production of erythropoietin by these cells was significantly enhanced by either lowering the PO2 in the incubation atmosphere or by adding cobalt chloride to the culture medium. Therefore, mesangial cells in culture may be considered as an in vitro system in which the regulation of erythropoietin production can be studied under well-defined conditions.

Animals↗
PubMed1983

Extraction of erythropoietin from isolated renal glomeruli of hypoxic rats.

We investigated whether erythropoietin (Ep) can be extracted from renal glomeruli of hypoxic rats. Hypoxia was induced in a hypobaric chamber at 0.42 atmospheres for usually 6 h. Glomeruli were isolated with a sieving technique from kidneys that were flushed free of blood. Ep activities in glomeruli homogenates were determined in the fetal mouse liver cell assay and in the hypoxia exposed mouse assay. We found in vitro erythropoietic activity of glomerular extracts, which increased about 25-fold during hypoxia. Incubation of the extracts with anti-Ep serum abolished the activity. Its binding characteristics on Wheat germ lectin. Ricinus communis lectin and DEAE-cellulose suggested that glomeruli contained Ep precursor(s) that lacked terminal sugar residues. Such an incomplete carbohydrate portion seems also compatible with the finding that glomerular extracts did not stimulate erythropoiesis in hypoxia exposed mice.

Animals↗
PubMed1982

A new candidate for the regulation of erythropoiesis. Insulin-like growth factor I.

The effect of pure human insulin-like growth factor I (IGF I) on the colony formation of late stage erythroid precursor cells (CFU-e) from fetal mouse liver and adult bone marrow was studied in a serum-free culture system. We found that IGF I in physiological concentrations stimulated erythroid colony formation. The combined effect of IGF I and erythropoietin was smaller than the sum of their single effects. The number of colonies induced by IGF I was linearly dependent on the number of plated cells. Our results indicate that IGF I is the first clearly defined mitogen that stimulates the late stages of erythroid differentiation independently of erythropoietin.

Animals↗
PubMed1982

Temporal pattern of erythropoietin titers in kidney tissue during hypoxic hypoxia.

Plasma titers of erythropoietin (Ep) are known to increase initially during hypoxia and to return then towards prehypoxia values. To find out if this pattern of plasma Ep might be related to changes in the production of the hormone, I have compared plasma with kidney Ep titers in hypoxic rats. Rats were exposed to hypoxia in a hypobaric chamber at 0.42 atm for various time intervals for up to 4 days. Kidney Ep titers were assayed in extracts from kidneys that had been flushed free of blood in situ. It was found that kidneys of normal rats do not store significant amounts of Ep. Kidney Ep titers increased transiently during hypoxia. They reached maximum values after 6h and then declined to almost undetectable levels at continued hypoxia. In the plasma, maximum values were found after 12-18h of hypoxia. Additional studies were done on the effects of discontinuous hypoxia. It was found that, even after 3 days of previous hypoxia exposure, plasma and kidney Ep titers increased again in rats when these were maintained intermittently in normoxia for 18 h. It is concluded that the rise and fall in plasma Ep titers during hypoxia reflect similar changes in kidney Ep production.

Animals↗
PubMed1982

Characterization of the pyruvate kinase which induces the low 2,3-DPG level of fetal rabbit red cells.

The low 2,3-disphosphoglycerate (2,3-DPG) level of fetal rabbit red cells has been attributed previously to a very high pyruvate kinase (PK) activity. The present report shows that the high PK activity is associated with a distinct fetal isozyme. Fetal and adult rabbit red cell PK were characterized by the methods recommended by the International Committee for Standardization in Haematology. Fetal red cell PK differed from the adult enzyme by its greater thermostability, lower affinities for phosphoenolpyruvate and ADP, higher nucleotide specificity and lower ATP inhibition. Marked electrophoretic differences were not detected. Our results indicate that there is a developmental change in red cell PK isozyme expression in the rabbit. We do not know, however, if this change arises at the gene level or from cell-age dependent postsynthetic modifications of the enzyme. But in view of the role of PK in the control of the 2,3-DPG level and thereby of the oxygen affinity of red blood cells, we assume that the physiological significance of the PK isozyme change is akin to that of the switch from fetal to adult hemoglobin in other species.

2,3-Diphosphoglycerate↗
PubMed1982

[Hemoglobins, XLVIII: the primary structure of hemoglobin of the Indian elephant (Elephas maximus, Proboscidea): beta 2 = Asn].

The primary structure of the hemoglobin of the Indian Elephant (Elephas maximus) is given. The sequence was determined automatically in a sequenator. By homologous comparison with adult human HbA, the alpha-chains differ by 24 exchanges and the beta-chains by 27 exchanges. Furthermore, we report p(O2)50 values with regard to altered contact sites with 2,3-bisphosphoglycerate in Indian elephant hemoglobin. Our findings explain the low p(O2)50 and the reduced interaction with 2,3-bisphosphoglycerate. Elephant hemoglobin has, like that of the Llama, only five phosphate binding sites. In addition, we have made an attempt to relate these results to aspects of respiratory physiology. Some implications of these biochemical and physiological results, concerning the Second Punic War and Hannibal's Alp transition, are given.

Amino Acid Sequence↗
PubMed1981

Demonstration of high levels of erythropoietin in rat kidneys following hypoxic hypoxia.

Controversial hypotheses exist as to whether hypoxic kidneys produce biologically active erythropoietin (Ep) or an inactive erythropoietic factor that generates Ep from plasma protein in the blood. To clarify the role of the kidney in Ep production we attempted to extract Ep from kidneys of normal and of hypoxia exposed (6 h at 0.42 atm) Sprague-Dawley rats. Ep was measured in the microsomal fraction of kidney homogenates, using the exhypoxic polycythemic mouse assay for Ep. The Ep content was also determined in kidneys that were flushed free of blood with isotonic phosphate-buffer prior to extirpation. We found 0.04 U Ep/g in blood-depleted kidneys of normal rats. Upon exposure of the animals to hypoxia the Ep level increased to 0.92 U/g kidney. Ep levels were significantly higher in the kidney cortex than in the medulla. The erythropoietic activity in renal extracts was not enhanced after incubation of samples with homologous serum. Ep extracted from hypoxic kidneys behaved identically with plasma-Ep in the following biochemical tests: heat stability, affinity chromatography, with wheat germ lectin, ion exchange chromatography, molecular sieve chromatography, and neuraminidase inactivation. These studies support the hypothesis that kidney cortex cells are capable of producing biologically active Ep.

Animals↗
PubMed1981

High oxygen affinity of maternal blood reduces fetal weight in rats.

In order to obtain information on the physiological significance of the difference in oxygen affinity between maternal and fetal blood, we have examined the effect of an acute increase of the oxygen affinity of maternal blood in pregnant rats, on fetal body weight, fetal brain and liver weights, placental weight, and the hematocrit of fetal blood. The increase in oxygen affinity was produced by exchange-transfusing pregnant rats on day 19 of gestation with blood that had been treated previously with sodium cyanate. As a result of the exchange transfusion, the difference in oxygen affinity between maternal and fetal blood essentially disappeared. Pregnant rats exchanged with normal blood served as controls. On day 21 of gestation, the fetal body weight and the fetal liver weight were significantly smaller by 18% and 25% respectively, in the group where the oxygen affinity of the maternal blood was acutely raised when compared to the controls. Also, the hematocrit of the fetal blood was significantly higher in the group where mothers had the high blood oxygen affinity. Placental weight and fetal brain weight were not significantly altered. We infer, that the reduction of fetal weight is due to fetal hypoxia which is caused by the abolishment of the difference in oxygen affinity between maternal and fetal blood. Human infants, whose birth weight is too small for their gestational age have a significantly increased postnatal mortality compared to babies with normal weight. We suppose that the increased mortality of newborns who are too small for their gestational age, represents a selective pressure that has favoured the evolution of a high oxygen affinity of fetal in comparison with maternal blood.

Animals↗
PubMed1981

Adaptation of hemoglobin function to subterranean life in the mole, Talpa europaea.

In order to understand the mechanism responsible for the high oxygen affinity of mole blood, we investigated in the mole. Talpa europaea, red cell parameters that determine hemoglobin function. We have found that the oxygen half saturation pressure (P50) of mole blood is 2.85 kPa (21.4 Torr) at pCO2 4.7 kPa, pH 7.4 and 37 degree C. The concentration of 2,3-diphosphoglycerate (2,3-DPG) averaged 5.3 mmol/l in red cells. In addition, we have determined P50 in hemoglobin solutions at various concentrations of 2,3-DPG at an assumed intraerythrocytic pH of 7.2 and 37 degree C. These data were used to calculate the association constants of 2,3-DPG to mole hemoglobin. P50 was 1,89 kPa (14.2 Torr) in hemoglobin solutions without 2,3-DPG. The response to 2,3-DPG was relatively low. Noteworthy, CO2 did not affect the oxygen affinity at constant pH in the presence of 2,3-DPG. Our results suggest that the high blood oxygen affinity of the mole can be attributed to a weak interaction of its hemoglobin with 2,3-DPG.

Adaptation, Physiological↗
PubMed1981

Regulation of red cell DPG metabolism in fetuses and adults.

We have compared red cell levels of 2,3-DPG in relation to the activities of certain glycolytic enzymes (DPGM, PK, PFK) between fetuses and adults in various rodents in order to find out the possible causes of the low intraerythrocytic concentration of 2,3-DPG in the fetal period. It was concluded that, in all species studied, 2,3-DPG synthesis was limited by a high activity of PK in fetal red cells. In addition, in species of the suborder Myomorpha, the activity of DPGM was lower in fetal red cells than in adults. In particular, the 2,3-DPG deficient fetal rat red cells completely lacked DPGM activity.

2,3-Diphosphoglycerate↗
PubMed1981

[Hemoglobins, XLIII: The primary structure of mole hemoglobin (Talpa europaea) (author's transl)].

The hemoglobin of the european mole (Talpa europaea) has only one component. The alpha- and beta-chains were separated by chromatography on CM 52 cellulose. The primary structures of both chains were mainly established on the tryptic peptides by automatic Edman degradation. The N-terminal regions were sequenced on the chains. Large C-terminal peptides could be isolated and sequenced after acidic hydrolysis of the Asp-Pro bond (alpha: 94/95, beta: 99/100). The peptides were aligned by their homology with human alpha- and beta-chains. A comparison with human hemoglobin shows an exchange of 18 amino acid residues in the alpha-chains and of 30 in the beta-chains. The substitutions in the surroundings of the heme and the contacts between the subunits are discussed. All amino acid residues responsible for the binding of 2,3-dihosphoglycerate are present. Nevertheless a high oxygen affinity and a reduced interaction with diphosphoglycerate are found in mole hemoglobin (Jelkmann, W., Oberthür, W., Kleinschmidt, T. & Braunitzer, G. (1981) Respir. Physiol., in press). According to the sequence a relaxed structure of the central cavity between the beta-chains can be the reason for the low interaction between phosphate and protein. The oxygen affinity is not only affected by the presence of diphosphoglycerate-binding sites in hemoglobin but also by the structure in this region of the molecule.

Amino Acid Sequence↗
PubMed1980

2,3-DPG levels in relation to red cell enzyme activities in rat fetuses and hypoxic newborns.

We have measured in red cells from fetal and adult Sprague-Dawley and Wistar rats the activities of phosphofructokinase (PFK), pyruvate kinase (PK) and diphosphoglyceromutase (DPGM) as key enzymes in the regulation of 2,3-diphosphoglycerate (2,3-DPG) levels to gather information on the possible causes of the low concentration of 2,3-DPG in fetal red cells. The most striking differences were seen with regard to PK and DPGM activities. The activity of PK was ten times higher in fetal compared to adult red cells, whereas red cell DPGM activity was absent in fetuses and high in adults. In addition, we studied postnatal changes in red cell PK and DPGm activities as well as in the 2,3-DPG concentration in Sprague-Dawley rats. The concentration of 2,3-DPG and the activity of DPGM in red cells increased to almost the adult value within 2 and 4 weeks after birth, respectively, while the activity of PK decreased concomitantly. The postnatal changes occurred similarly, when newborn rats grew up under conditions of hypoxic hypoxia at 0.46 atm (pO2 = 9.2 kPa). Our studies support the hypothesis that postnatal changes in 2,3-DPG levels are due to changes in the activity of certain glycolytic enzymes and that the switch from fetal-type to adult-type red cells follows a genetically determined time course.

Aging↗
PubMed1980

beta 2-Adrenergic stimulation of erythropoiesis in busulfan treated mice.

The capability of chronic beta 2-adrenoceptor activation to effectively stimulate erythrocyte production in vivo was investigated in mice which had been treated with the hematopoiesis inhibiting agent busulfan. A relatively low dose (5 mg/kg i.p.) of busulfan produced moderate depression of erythropoiesis 10 days after a single injection, as determined by 59Fe-incorporation into erythrocytes. Administration of albuterol (1 mg/kg s.c. twice daily), a selective beta 2-adrenergic agonist, significantly enhanced erythropoiesis for 5--10 days after the injection of busulfan. In a long-term study with albuterol at the same dose a significant increase in hematocrit values as well as in the circulating erythrocyte mass was found in busulfan (5 mg/kg i.p. weekly) treated mice when compared to saline-busulfan treated control mice. Simultaneous injections of the beta-adrenergic blocking agent propanolol (4 mg/kg i.p.) diminished the effect of albuterol on erythropoiesis. Albuterol at a lower dose (0.1 mg/kg) had no significant effect on erythrocyte mass. In view of recent findings, which have shown that the proliferation of the pluripotent hemopoietic stem cell pool is blocked by busulfan, it is concluded that the main site of beta 2-adrenergic action on erythropoiesis is on the erythroid committed stem cell pool. In addition, enhanced release of erythropoietin from the kidney following the application of albuterol may contribute to beta 2-adrenergic stimulation of erythropoiesis.

Albuterol↗