Age-related effect of melatonin on permeability transition pore opening in rat brain mitochondria

Abstract

Aging is accompanied by mitochondrial dysfunction related with lowering of the respiratory com� plex activity and decrease of ATP synthesis, as well as by an enhancement of oxidative stress and increased sensitivity to mitochondrial permeability transition pore (mPTP) opening in mitochondral triggering the programmed cell death. In the present work we studied the effect of natural antioxidant (melatonin) on parameters of mPTP detected in nonsynaptic mitoch ondria isolated from the brain of young and old rats (3 and 18 months, resp.) with different melatonin treatments; namely, melatonin was either directly applied to the mitochondrial suspension or chronically administered to rats with drinking water. The data obtained have shown that mitochondria isolated from brain of old rats were more susceptive to induction of mPTP. Melatonin added directly to suspension of brain mitochondria isolated from young rats demonstrated a pro� apoptotic effect. A prolonged chronical treatment with melatonin of old rats produced an antiapoptotic pro� tective effect. Nonsynaptic mitochondria isolated from the brain of old rats treated with melatonin were more resistant to the mPTP opening and demonstrated the activation of respiration of mitochondria as com� pared to the untreated rats.