Autocrine function of erythropoietin in IGF-1-induced erythropoietin biosynthesis.
Insulin-like growth factor-1 (IGF-1) and erythropoietin (EPO) are induced in brain cells after brain ischemia and show synergistic neuroprotective effects. In LN215 astrocytoma cells, IGF-1 induced the activation of hypoxia-inducible factor-1, leading to increases in EPO mRNA levels and the secretion of EPO. Interestingly, blocking the potential action of secreted EPO on LN215 cells with EPO antibody, EPO receptor antibody, and soluble EPO receptor significantly suppressed the effect of IGF-1 on the biosynthesis of EPO. Synergistic action between IGF-1 and recombinant human EPO in the astrocytic production of EPO was observed. These data suggest that the IGF-1-EPO production/secretion process initiates a positive feedback loop of EPO biosynthesis in astrocytes, providing a molecular link between the two neuroprotective cytokines.
BK21 Project for Medical Science, Brain Research Institute, Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
Insook
I
Kim
Chul Hoon
CH
Kim
Yeong Shin
YS
Yim
Young Soo
YS
Ahn
D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019898:Autocrine Communication / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation
D000906:Antibodies; D051793:Hypoxia-Inducible Factor 1; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D007334:Insulin-Like Growth Factor I