ADENOSINE-TRIPHOSPHATE DEGRADATION PRODUCTS AFTER OXIDATIVE STRESS AND METABOLIC DYSFUNCTION IN CULTURED RETINAL CELLS

The alteration in energy metabolic products was analyzed in cultured r etinal cells submitted to oxidative stress, hypoxia, glucopenia, or is chemia-like conditions, Ischemia highly reduced cellular ATP and incre ased AMP formation, without significant changes in ADP, Ischemia induc ed a significant increase in extracellular adenosine (ADO) and hypoxan thine (HYP), and to a lesser extent inosine (INO). Glucopenia reduced cellular ATP by about two-to threefold, which was not compensated for by AMP formation, Under glucopenia, extracellular ADO and HYP were sig nificantly increased, although a major increase in extracellular INO w as observed. 5-(4-Nitrobenzyl)-6-thioinosine (10 mu M) reduced extrace llular ADO during glucopenia or ischemia by similar to 80%, indicating that ADO accumulation occurs mainly via the transporter, Intracellula r ATP, ADP, or AMP and extracellular ADO, INO, or HYP were not apparen tly changed after oxidative stress or hypoxia. Nevertheless, in the pr esence of 10 mu M erythro-9-(2-hydroxy-3-nonyl) adenosine, oxidative s tress was shown to increase significantly the accumulation of ADO, whi ch was reduced in the presence of 200 mu M alpha,beta-methyleneadenosi ne 5'-diphosphate, suggesting that ADO accumulation after oxidative st ress may result from extracellular degradation of adenine nucleotides, The increase in ADO accumulation resulting from the depletion of cell ular ATP was directly related to the release of endogenous glutamate o ccurring through a Ca2+-independent pathway after ischemia. Increased metabolic products derived from ATP are suggested to exert a modulatin g effect against excitotoxic neuronal death.