ENHANCED LIPID-PEROXIDATION BY EXTRACELLULAR ATP IN PC12 CELLS

Recently we have demonstrated that extracellular ATP acts as an excita tory neurotransmitter and enhances cell death in the presence of ferro us ions. By using a newly developed cis-parinaric acid fluorescence te chnique, we demonstrated that ATP, in a dose dependent manner, enhance d the increased membrane lipid peroxidation in PC12 cells when cells w ere incubated with micromolar FeCl2/DTP. P-2 purinoceptor agonists, al pha beta-methylene ATP and 2-methylthio-ATP, induced PC12 cell lipid p eroxidation, but to a lesser extent than ATP. ATP-induced Ca2+ influx via P-2 purinoceptor activation significantly increased the intracellu lar Ca2+ concentration, which may have triggered a free radical genera ting cascade(s), and led to membrane lipid peroxidation and cell death . Since oxidative stress has been implicated in certain neurodegenerat ive diseases such as aging, extracellular ATP may contribute to neuron al cell death by an oxidative mechanism involving lipid peroxidation.