title: Nerve growth factor and brain-derived neurotrophic factor but not granulocyte colony-stimulating factor, nimodipine and dizocilpine, require ATP for neuroprotective activity after oxygen-glucose deprivation of primary neurons.
abstract: In previous work, we have demonstrated by radiolabeling, mass spectrometry and site-directed mutagenesis that nerve growth factor (NGF) as well as brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 2 (FGF2) are capable of ATP-binding and that this binding appears to be essential for their neuroprotective activity. In this study, we attempted to shed some light on the question whether ATP is a general prerequisite for neuroprotection. Therefore, we used the non-ATP-binding granulocyte colony-stimulating factor (GCSF), the calcium antagonist nimodipine and the NMDA antagonist dizocilpine to find out whether they need ATP for neuroprotection comparable to NGF and BDNF. However, ATP was not necessary for the neuroprotective effects of GCSF, nimodipine and dizocilpine on primary cultures of rat cortical neurons damaged by oxygen-glucose deprivation whereas neuroprotection was demonstrable for NGF and BDNF only when ATP was present in the culture medium at a concentration higher than ca. 0.4nmol/l. In circular dichroism studies ATP caused changes of the secondary structure of NGF but not of GCSF. Taken together, we suggest that ATP is not a general prerequisite for neuroprotectivity but some growth factors like NGF and BDNF can stimulate their receptors only if they have bound ATP.
authors.affiliation: Institut für Pharmazeutische und Medizinische Chemie, Westfälische Wilhelms-Universität, 48149 Münster, Germany.
authors.forename: Katja B
authors.initials: KB
authors.lastname: Ferenz
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gast
authors.forename: Karsten
authors.initials: K
authors.lastname: Rose
authors.forename: Indra E
authors.initials: IE
authors.lastname: Finger
authors.forename: Anja
authors.initials: A
authors.lastname: Hasche
authors.forename: Josef
authors.initials: J
authors.lastname: Krieglstein
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D000465:Algorithms; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects*; D002478:Cells, Cultured; D002942:Circular Dichroism; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000172:deficiency*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D020932:Nerve Growth Factor / Q000737:chemistry / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002121:Calcium Channel Blockers; D018696:Neuroprotective Agents; D016179:Granulocyte Colony-Stimulating Factor; D009553:Nimodipine; D016291:Dizocilpine Maleate; D000255:Adenosine Triphosphate; D020932:Nerve Growth Factor; D005947:Glucose