Through control of the oxidative stress generated from
aerobic respiration, mGSH is essential in the maintenance of
mitochondrial function. mGSH is particularly relevant in the
disposal of hydrogen peroxide generated from superoxide
anion by MnSOD, which otherwise may oxidize SH groups
from proteins or peroxidize mitochondrial lipids. The
oxidative modifications of mitochondrial components may
then contribute to MMP leading to cell death, either by
necrosis or apoptosis (Fig. 2). The significance of mGSH
has been best illustrated in conditions in which its depletion
has been shown to sensitize cells to cytokine or druginduced
cell death. Since mGSH originates from a carriermediated
process, its further characterization and better
understanding may provide novel approaches to increase
mGSH levels and thus protect cells against drug-induced
oxidant stress and cell death. In addition, detailed knowledge
of the mechanism involved in mGSH depletion in
particular cases may reveal alternatives to replenish mGSH
when the use of GSH precursors are not effective as
exemplified by the impaired mitochondrial GSH transport
by alcohol intake. Thus, the development of pharmacological
armamentarium to increase mGSH may be of significance
in the treatment of human diseases.
Through control of the oxidative stress generated from
aerobic respiration, mGSH is essential in the maintenance of
mitochondrial function. mGSH is particularly relevant in the
disposal of hydrogen peroxide generated from superoxide
anion by MnSOD, which otherwise may oxidize SH groups
from proteins or peroxidize mitochondrial lipids. The
oxidative modifications of mitochondrial components may
then contribute to MMP leading to cell death, either by
necrosis or apoptosis (Fig. 2). The significance of mGSH
has been best illustrated in conditions in which its depletion
has been shown to sensitize cells to cytokine or druginduced
cell death. Since mGSH originates from a carriermediated
process, its further characterization and better
understanding may provide novel approaches to increase
mGSH levels and thus protect cells against drug-induced
oxidant stress and cell death. In addition, detailed knowledge
of the mechanism involved in mGSH depletion in
particular cases may reveal alternatives to replenish mGSH
when the use of GSH precursors are not effective as
exemplified by the impaired mitochondrial GSH transport
by alcohol intake. Thus, the development of pharmacological
armamentarium to increase mGSH may be of significance
in the treatment of human diseases.
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