Inflammation marker 7,8-dihydroneopterin induces apoptosis of neurons and glial cells: a potential contribution to neurodegenerative processes.
Since neopterin is elevated in the cerebrospinal fluid of patients with inflammatory neurological disorders we investigated the source of neopterin in the brain and a possible contribution of biological active pteridines to the development of brain lesions. Astrocytic, neuronal and microglial cell lines were shown to be negative for neopterin production even after stimulation with interferon-gamma (IFN-gamma) indicating that infiltrating monocytes/macrophages might be responsible for neopterin level in CNS. Whereas neopterin did not affect viability of brain cells, its derivative 7,8-dihydroneopterin (7,8-DHN) induced dose-dependently cellular apoptosis in astrocytes and neurons probably via enhancement of nitric oxide synthase (iNOS) expression. This mechanism might represent a possible link between inflammation in the brain and neurodegeneration.
Speth
C
C
Institute of Hygiene and Social Medicine, University of Innsbruck, Austria. cornelia.speth@uibk.ac.at
Stöckl
G
G
Fuchs
D
D
Wirleitner
B
B
Widner
B
B
Würzner
R
R
Mohsenipour
I
I
Lass-Flörl
C
C
Dierich
M P
MP
D000135:Acid Phosphatase / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D019798:Neopterin / Q000032:analysis / Q000494:pharmacology / Q000031:analogs & derivatives; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011621:Pteridines / Q000494:pharmacology*
D000975:Antioxidants; D011621:Pteridines; C000976:7,8-dihydroneopterin; D019798:Neopterin; D007371:Interferon-gamma; D000135:Acid Phosphatase