Heparin-binding epidermal growth factor-like growth factor (HB-EGF) regulates survival of midbrain dopaminergic neurons.
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF-family of ligands signaling via the EGF-receptor tyrosine kinase. In the present study we show that HB-EGF which is expressed in close proximity of developing mesencephalic dopaminergic neurons promotes the survival of TH-positive neurons in vitro. The survival promoting effect of HB-EGF is mediated via astroglial cells and utilizes the MAPK as well as the Akt-signaling pathway. Most notably endogenous HB-EGF significantly contributes to the survival of TH-+ neurons in control cultures, suggesting a relevant developmental role of HB-EGF for dopaminergic neurons. These findings indicate that HB-EGF may be an important molecule for developing dopaminergic neurons of the ventral midbrain.
Farkas
L M
LM
Neuroanatomy, University of Heidelberg, Heidelberg, Federal Republic of Germany.
Krieglstein
K
K
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005333:Fetus; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism* / Q000503:physiopathology; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013378:Substantia Nigra / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism
D000906:Antibodies; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D004298:Dopamine