Hypoxia affects the physiological behavior of rat cortical synaptosomes.
Nerve cells, especially synaptosomes, are very susceptible to hypoxia and the subsequent oxidative stress. In this paper, we examined the effects of hypoxia (93% N(2):2% O(2):5% CO(2), v/v/v) on rat cortical synaptosomes by evaluating modifications of synaptosomal mitochondrial respiration rate and ATP production, membrane potential, intrasynaptosomal mitochondrial Ca(2+) concentration ([Ca(2+)](i)), and desferoxamine-chelatable free iron and esterified F2-isoprostane levels after different periods of hypoxia and after 30 min of reoxygenation. Oxygen consumption decreased significantly during 120 min of hypoxia and was restored after reoxygenation. At the same time, ATP production decreased and remained significantly lower even after reoxygenation. This involved a depolarization of the synaptosomal mitochondrial membrane, although the [Ca(2+)](i) remained practically unchanged. Indeed, iron and F2-isoprostane levels, representing useful prediction markers for neurodevelopmental outcome, increased significantly after hypoxia, and there was a strong correlation between the two variables. On the whole our results indicate that synaptosomal mitochondria undergo mitoptosis after 2 h of hypoxia.
Aldinucci
Carlo
C
Department of Physiology, University of Siena, 53100 Siena, Italy.
Carretta
Alessandra
A
Ciccoli
Lucia
L
Leoncini
Silvia
S
Signorini
Cinzia
C
Buonocore
Giuseppe
G
Pessina
Gian Paolo
GP
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000503:physiopathology*; D028441:F2-Isoprostanes / Q000032:analysis / Q000378:metabolism; D002534:Hypoxia, Brain / Q000503:physiopathology*; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism; D010100:Oxygen / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000737:chemistry / Q000378:metabolism*
D028441:F2-Isoprostanes; D000255:Adenosine Triphosphate; D010100:Oxygen; D002118:Calcium