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- W1990481263 abstract "Melatonin protects cells against oxidative stress-induced apoptosis due primarily to its ability to effectively scavenge pathological condition-augmented generation of mitochondrial reactive oxygen species (mROS). Once produced, mROS in addition to indiscriminately damage mitochondrial components they crucially activate directly the mitochondrial permeability transition (MPT), one of the critical mechanisms for initiating post mitochondrial apoptotic signaling. Whether or not melatonin targets directly the MPT, however, remains inconclusive, particularly during oxidative stress. Thus, we investigated this possibility of an “oxidation free Ca2+ stress” in the presence of vitamin E after ionomycin exposure as a sole Ca2+-mediated MPT in order to exclude melatonin's primary antioxidative effects as well as Ca2+-mediated oxidative stress. With the application of laser scanning fluorescence imaging microscopy, we visualized for the first time multiple mitochondrial protections provided by melatonin during Ca2+ stress in cultured rat brain astrocytes RBA-1. Melatonin, due to its primary antioxidative actions, completely prevented mCa2+-induced mROS formation for a reduced mROS-activated MPT during ionomycin exposure. In the presence of vitamin E, melatonin, significantly reduced cyclosporin A (CsA) sensitive mitochondrial depolarization and MPT during ionomycin exposure suggesting its direct targeting of the MPT. Moreover, when the MPT was inhibited by CsA, melatonin reduced further MPT-independent mitochondrial depolarization and apoptosis suggesting its targeting beyond the MPT. As astrocytes play active role in regulating neuronal pathophysiology, these multiple mitochondrial protections provided by melatonin against mCa2+- and/or mROS-mediated apoptosis may thus be crucial for the future therapeutic prevention and treatment of astrocyte-mediated neurodegeneration in the CNS." @default.
- W1990481263 created "2016-06-24" @default.
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- W1990481263 date "2010-01-01" @default.
- W1990481263 modified "2023-09-27" @default.
- W1990481263 title "Visualization of Melatonin's Multiple Mitochondrial Levels of Protection Against Mitochondrial Ca2+-Mediated Permeability Transition and Beyond in Rat Brain Astrocytes" @default.
- W1990481263 doi "https://doi.org/10.1016/j.bpj.2009.12.2038" @default.
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