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Mitochondria‐targeted peptide inhibits H2O2‐induced mitochondrial Ca2+ overload in HeLa cells
Author(s) -
Greene Vilma,
Birk Alexander,
Szeto Hazel
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1118
Subject(s) - mitochondrial permeability transition pore , mitochondrion , aequorin , cytochrome c , cytosol , intracellular , apoptosis , oxidative stress , mitochondrial apoptosis induced channel , microbiology and biotechnology , chemistry , calcium , cytoplasm , membrane potential , programmed cell death , calcium in biology , inner mitochondrial membrane , biochemistry , biology , organic chemistry , enzyme
Treatment of cells with H 2 O 2 leads to Ca 2+ release from intracellular stores and result in elevated Ca 2+ levels in the cytosol ([Ca 2+ ] c ) and mitochondria ([Ca 2+ ] m ). Increased [Ca 2+ ] m can result in mitochondria permeability transition (MPT), mitochondrial swelling, cytochrome c release, and apoptosis. A series of aromatic‐cationic peptides developed in this lab were shown to target the inner mitochondrial membrane and prevent calcium‐induced MPT, and inhibit apoptosis in cells treated with t ‐butylhydroperoxide. This study was designed to determine if these peptides prevent [Ca 2+ ] m overload in cells treated with H 2 O 2 . [Ca 2+ ] m and [Ca 2+ ] c were measured using aequorin targeted to the mitochondria and cytoplasm, respectively. Addition of 1 mM H 2 O 2 caused a rapid rise in both [Ca 2+ ] c and [Ca 2+ ] m . Pretreatment with 1 nM of SS‐19 for 30 minutes prior to addition of 1 mM H 2 O 2 reduced the elevation in [Ca 2+ ] m caused by H 2 O 2 and this was associated with increased [Ca 2+ ] c . These results show that SS‐19 limits mitochondrial calcium loading resulting from H 2 O 2 ‐induced release of Ca 2+ from intracellular stores. Evidence to date suggests that SS‐19 and related peptides prevent Ca 2+ overload in mitochondria induced by oxidative stress, maintaining mitochondrial integrity, and protecting against oxidative cell death. This work was supported by NIH DA‐08924, NS‐48295, and DA‐007274 (VG)