Abstract
Redox factor-1 (Ref-1) is a multifunctional protein involved in DNA base excision repair (BER) and transcription factor modification. By the use of retrovirus-delivered shRNA, we effectively suppressed endogenous Ref-1 expression in human embryonic kidney (HEK) 293 cells. Our results showed that downregulation of Ref-1 rendered cells more sensitive to H(2)O(2)-induced apoptosis. In this process, the absence of Ref-1 decreased the ratio of Bcl-2/Bax protein expression, which resulted in cytochrome c release and caspase-3 activation. These data indicate that constitutive Ref-1 is required for cellular defense and that this protective function is dependent on its role in the regulation of Bcl-2 family proteins.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects*
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Apoptosis / genetics
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Base Sequence
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Caspase 3 / metabolism
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Cell Line
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Cytochromes c / metabolism
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DNA-(Apurinic or Apyrimidinic Site) Lyase / genetics*
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DNA-(Apurinic or Apyrimidinic Site) Lyase / metabolism
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Enzyme Activation
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Gene Silencing*
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Humans
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Hydrogen Peroxide / toxicity*
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Oxidative Stress / genetics
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Proto-Oncogene Proteins c-bcl-2 / genetics
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism*
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Retroviridae / genetics*
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bcl-2-Associated X Protein / genetics
Substances
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Proto-Oncogene Proteins c-bcl-2
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RNA, Small Interfering
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bcl-2-Associated X Protein
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Cytochromes c
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Hydrogen Peroxide
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Caspase 3
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APEX1 protein, human
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DNA-(Apurinic or Apyrimidinic Site) Lyase