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Oxidative stress in...
Oxidative stress induces nucleo-cytoplasmic translocation of pancreatic transcription factor PDX-1 through activation of c-Jun NH(2)-terminal kinase
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Kawamori, D (författare)
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Kajimoto, Y (författare)
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Kaneto, H (författare)
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Umayahara, Y (författare)
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Fujitani, Y (författare)
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Miyatsuka, T (författare)
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Watada, H (författare)
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- Leibiger, IB (författare)
- Karolinska Institutet
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Yamasaki, Y (författare)
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Hori, M (författare)
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(creator_code:org_t)
- American Diabetes Association, 2003
- 2003
- Engelska.
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 52:12, s. 2896-2904
- Relaterad länk:
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http://diabetes.diab...
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http://kipublication...
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https://doi.org/10.2...
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Abstract
Ämnesord
Stäng
- Oxidative stress is induced in pancreatic β-cells under diabetic conditions and causes β-cell dysfunction. Antioxidant treatment of diabetic animals leads to recovery of insulin biosynthesis and increases the expression of its controlling transcription factor, pancreatic duodenal homeobox-1 (PDX-1), in pancreatic β-cells. Here, we show that PDX-1 is translocated from the nuclei to the cytoplasm of pancreatic β-cells in response to oxidative stress. When oxidative stress was charged upon β-cell-derived HIT-T15 cells, both endogenous PDX-1 and exogenously introduced green fluorescent protein-tagged PDX-1 moved from the nuclei to the cytoplasm. The addition of a dominant negative form of c-Jun NH2-terminal kinase (JNK) inhibited oxidative stress-induced PDX-1 translocation, suggesting an essential role of JNK in mediating this phenomenon. Whereas the nuclear localization signal (NLS) in PDX-1 was not affected by oxidative stress, leptomycin B, a specific inhibitor of the classical leucine-rich nuclear export signal (NES), inhibited nucleo-cytoplasmic translocation of PDX-1 induced by oxidative stress. Moreover, we identified an NES at position 82-94 of the mouse PDX-1 protein. Thus, our present results revealed a novel mechanism that negatively regulates PDX-1 function. The identification of the NES, which overrides the function of the NLS in an oxidative stress-responsive, JNK-dependent manner, supports the complicated regulation of PDX-1 function in vivo and may further the understanding of β-cell pathophysiology in diabetes.
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
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Diabetes
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Till lärosätets databas
- Av författaren/redakt...
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Kawamori, D
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Kajimoto, Y
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Kaneto, H
-
Umayahara, Y
-
Fujitani, Y
-
Miyatsuka, T
-
visa fler...
-
Watada, H
-
Leibiger, IB
-
Yamasaki, Y
-
Hori, M
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visa färre...
- Artiklar i publikationen
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Diabetes
- Av lärosätet
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Karolinska Institutet