Fibroblast growth factor 2 requires complex formation with ATP for neuroprotective activity

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• Fibroblast growth factor (FGF2) exhibits known neurotrophic and neuroprotective properties.
• The precise molecular mechanism underlying FGF2's neuroprotection remains incompletely understood.

Purpose of the Study:

• To investigate the essential role of adenosine triphosphate (ATP) binding in mediating the neuroprotective effects of FGF2.
• To determine if FGF2 alone or a complex with ATP is responsible for neuroprotection.

Main Methods:

• Primary cultures of embryonic rat cortical neurons were utilized.
• Adenosine triphosphate (ATP) levels were modulated using enzymes like alkaline phosphatase, ATPase, and apyrase.
• Neuroprotection was assessed under conditions of varying ATP concentrations and with stable ATP analogs (gammaS-ATP).

Main Results:

• Reducing extracellular ATP concentration below 1 nM abolished the neuroprotective effect of FGF2.
• FGF2 retained its neuroprotective capacity when a stable ATP analog, gammaS-ATP, was used, which is resistant to enzymatic cleavage.
• Enzymatic depletion of ATP below critical levels by ATPase and apyrase also eliminated FGF2's neuroprotective activity.

Conclusions:

• The FGF2/ATP complex, rather than FGF2 in isolation, is the active mediator of neuroprotection in cortical neurons.
• This finding elucidates a critical molecular requirement for FGF2-mediated neuroprotection, highlighting the importance of ATP binding.