L-PGDS (betatrace protein) inhibits astrocyte proliferation and mitochondrial ATP production in vitro.
L-PGDS is the most abundant protein present in the cerebrospinal fluid (CSF). Although CSF was believed to be homogenous in content, a previous study has showed that a marked concentration gradient of L-PGDS exists between the spinal CSF and the CSF in the subarachnoid space of patients with optic nerve disease (papilledema and normal-tension glaucoma). Astrocytes play a critical role in maintaining the integrity of axon function in the central nervous system and specifically in the optic nerve, and we therefore investigated the biochemical effects of L-PGDS on the proliferation of astrocytes and on the production of adenosine triphosphate (ATP) by astrocyte mitochondria. We found an inhibitory effect of L-PGDS on both proliferation of astrocytes and production of astrocyte ATP. The concentrations that inhibited astrocyte proliferation and ATP production were in the range measured in patients with idiopathic intracranial hypertension and in patients with normal-tension glaucoma. As the CSF is in contact with axons and mitochondria of the optic nerve (Bristow et al. Archives of Ophthalmology, 120, 791-796, 2002), we postulate that a change in the concentration of CSF protein such as L-PGDS could exercise a harmful effect on these structures.
Xin
Xiaorong
X
University Eye Clinic, Basel, Switzerland.
Huber
Andreas
A
Meyer
Peter
P
Flammer
Josef
J
Neutzner
Albert
A
Miller
Neil R
NR
Killer
Hanspeter E
HE
D000255:Adenosine Triphosphate / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001369:Axons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005901:Glaucoma / Q000134:cerebrospinal fluid / Q000503:physiopathology; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000134:cerebrospinal fluid* / Q000494:pharmacology; D054834:Lipocalins / Q000134:cerebrospinal fluid* / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009900:Optic Nerve / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D009901:Optic Nerve Diseases / Q000134:cerebrospinal fluid* / Q000503:physiopathology; D011559:Pseudotumor Cerebri / Q000134:cerebrospinal fluid / Q000503:physiopathology; D013346:Subarachnoid Space / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology
D054834:Lipocalins; D000255:Adenosine Triphosphate; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase