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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2010.1
- 수록면
- 639 - 650 (12page)
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An abrupt increase of intracellular Ca2+ is observed in cells under hypoxic or oxidatively stressed conditions.
The dysregulated increase of cytosolic Ca2+ triggers apoptotic cell death through mitochondrial swelling and activation of Ca2+-dependent enzymes. Transglutaminase 2 (TG2) is a Ca2+-dependent enzyme that catalyzes transamidation reaction producing cross-linked and polyaminated proteins. TG2 activity is known to be involved in the apoptotic process. However, the pro-apoptotic role of TG2 is still controversial. In this study, we investigate the role of TG2 in apoptosis induced by Ca2+-overload. Overexpression of TG2 inhibited the A23187-induced apoptosis through suppression of caspase-3 and -9 activities, cytochrome c release into cytosol, and mitochondria membrane depolarization. Conversely, down-regulation of TG2caused the increases of cell death, caspase-3 activity and cytochrome c in cytosol in response to Ca2+-overload. Western blot analysis of Bcl-2 family proteins showed that TG2 reduced the expression level of Bax protein. Moreover, overexpression of Bax abrogated the anti-apoptotic effect of TG2, indicating that TG2-mediated suppression of Bax is responsible for inhibiting cell death under Ca2+-overloaded conditions.
Our findings revealed a novel anti-apoptotic pathway involving TG2, and suggested the induction of TG2 as a novel strategy for promoting cell survival in diseases such as ischemia and neurodegeneration.
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참고문헌 (26)
참고문헌 신청
Acehan D / 2002 / Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation / Mol Cell 9 : 423 ~ 432
Akimov SS / 2000 / Tissue transglutaminase is an integrin-binding adhesion coreceptor for fibronectin / J Cell Biol 148 : 825 ~ 838
Antonyak MA / 2001 / Effects of tissue transglutaminase on retinoic acid-induced cellular differentiation and protection against apoptosis / J Biol Chem 276 : 33582 ~ 33587
Antonyak MA / 2003 / Activation of the Ras-ERK pathway inhibits retinoic acid-induced stimulation of tissue transglutaminase expression in NIH3T3 cells / J Biol Chem 278 : 15
Antonyak MA / 2004 / Augmentation of tissue transglutaminase expression and activation by epidermal growth factor inhibit doxorubicin-induced apoptosis in human breast cancer
Akimov SS / 2000 / Tissue transglutaminase is an integrin-binding adhesion coreceptor for fibronectin / J Cell Biol 148 : 825 ~ 838
Antonyak MA / 2001 / Effects of tissue transglutaminase on retinoic acid-induced cellular differentiation and protection against apoptosis / J Biol Chem 276 : 33582 ~ 33587
Antonyak MA / 2003 / Activation of the Ras-ERK pathway inhibits retinoic acid-induced stimulation of tissue transglutaminase expression in NIH3T3 cells / J Biol Chem 278 : 15
Antonyak MA / 2004 / Augmentation of tissue transglutaminase expression and activation by epidermal growth factor inhibit doxorubicin-induced apoptosis in human breast cancer
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