Melatonin rescues cell respiration impaired by hypoxia/reoxygenation in aortic endothelial cells and affects the mitochondrial bioenergetics targeting the F1FO-ATPase.
Study Goal
The researchers aimed to evaluate melatonin's potential as a molecular therapy to counteract mitochondrial dysfunction caused by hypoxia/reoxygenation (H/R) in aortic endothelial cells.
Results Summary
Melatonin reduced superoxide anion production and desensitized mitochondrial permeability transition pore (mPTP) opening, likely through direct interaction with the F1 domain of Ca2+-activated F1FO-ATPase. It also rescued impaired bioenergetics and oxidative stress in cells affected by H/R injury.
Population
Porcine aortic endothelial cells (pAECs)
Effective Dosage
Not available
Duration
Not specified
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
melatonin | decrease | mitochondrial permeability transition pore (mPTP) opening | aortic endothelial cells (pAECs) | - | undergoes a desensitizing action | #1 |
melatonin | decrease | superoxide anion production in mitochondria | aortic endothelial cells (pAECs) | - | reduction | #2 |
melatonin | decrease | ATPase activity of the purified F1 domain | - | - | inhibition | #3 |
melatonin treatment | increase | impairment of bioenergetics parameters in pAECs metabolism | aortic endothelial cells (pAECs) | - | rescued | #4 |
melatonin treatment | decrease | increase of oxidative stress arising by H/R injury | aortic endothelial cells (pAECs) | - | rescued | #5 |
Melatonin is evaluated as a potential molecular therapy to counteract mitochondrial dysfunction caused by hypoxia/reoxygenation (H/R) in aortic endothelial cells (pAECs). The mitochondrial permeability transition pore (mPTP) opening undergoes a desensitizing action coupled with a reduction of superoxide anion production in mitochondria treated with melatonin. The effect on mPTP has been attributed to the direct interaction of melatonin with the hydrophilic F1 domain of Ca2+-activated F1FO-ATPase. Mutual exclusion analysis highlights an overlapping binding site between melatonin and the specific F1 inhibitor NBD-Cl. The results are corroborated by melatonin inhibition of ATPase activity of the purified F1 domain in the presence of Ca2+, but not in the presence of natural cofactor Mg2+. Moreover, the impairment of bioenergetics parameters in pAECs metabolism and the increase of oxidative stress arising by H/R injury have been rescued in cells protected by melatonin treatment.