SCHOLZ, H and BAIER, W and RATCLIFFE, P and ECKARDT, K and ZAPF, J and KURTZ, A and BAUER, C (1992) INSULIN-LIKE GROWTH-FACTORS DECREASE OXYGEN-REGULATED ERYTHROPOIETIN PRODUCTION BY HUMAN HEPATOMA-CELLS (HEP G2). AMERICAN JOURNAL OF PHYSIOLOGY, 263 (2). C474-C479. ISSN 0002-9513,
Full text not available from this repository.Abstract
We examined the effects of insulin-like growth factors (IGFs) and insulin on erythropoietin (EPO) production by human hepatoma cells (Hep G2). Compared with normoxia (20% O2), EPO production by Hep G2 cells during a 72-h incubation was stimulated fivefold by exposure to low oxygen tension (1% O2) and nearly threefold by exposure to cobalt chloride (100-mu-M). IGF-I caused a concentration-dependent attenuation of EPO formation under normoxic conditions and inhibited (maximally 50%) EPO production stimulated by either low oxygen tension or cobalt [half-maximal effect (ED50) almost-equal-to 5 nM]. The increase of EPO mRNA levels in response to hypoxia was significantly reduced by IGF-I. Similarly to IGF-I, IGF-IL (ED50 almost-equal-to 8 nM) and insulin (ED50 almost-equal-to 80 nM) also inhibited EPO formation in Hep G2 cells. IGF-I (100 pM-100 nM) stimulated the incorporation of radiolabeled alanine as a measure for total protein synthesis, H-3-labeled thymidine incorporation into DNA, and glycogen synthesis at 20 and 1% O2 in a concentration-dependent fashion. IGF-I exhibited a high affinity for the IGF-I receptor (apparent K(d) almost-equal-to 3 nM). Unlabeled insulin was >100-fold less potent than IGF-I in competing for I-125-IGF-I binding (apparent K(d) almost-equal-to 360 nM). Conversely, insulin bound to the insulin receptor with high affinity (apparent K(d) almost-equal-to 0.3 nM), whereas IGF-I was <1% as potent in competing for I-125-insulin binding. In summary, IGFs and insulin exert a negative control function on oxygen-regulated EPO production in Hep G2 cells. The inhibitory effect of IGFs and insulin on EPO formation appears to be mediated via the IGF-I receptor.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FACTOR-I; MESSENGER-RNA; LINE; PHOSPHORYLATION; PROTECTION; RECEPTORS; PROTEINS; SERUM; RATS; IGF; HYPOXIA; COBALT; RADIOIMMUNOASSAY |
| Depositing User: | Dr. Gernot Deinzer |
| Last Modified: | 19 Oct 2022 08:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/54430 |
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