Role of JNK activation in pancreatic β-cell death by streptozotocin
- Cheon, Hwanju Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea - Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea
- Cho, Jae Min Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Kim, Sunshin Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Baek, Seung-Hoon Department of Neurology and Ophthalmology, Michigan State University, East Lansing, MI, USA
- Lee, Moon-Kyu Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Kim, Kwang-Won Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Yu, Seong-Woon Department of Neurology and Ophthalmology, Michigan State University, East Lansing, MI, USA - Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA
- Solinas, Giovanni Department of Medicine, Division of Physiology, University of Fribourg, Switzerland
- Kim, Soung Soo Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea
- Lee, Myung-Shik Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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20.02.2010
Published in:
- Molecular and Cellular Endocrinology. - 2010, vol. 321, no. 2, p. 131-137
English
c-Jun N-terminal kinase (JNK) is activated by cellular stress and plays critical roles in diverse types of cell death. However, role of JNK in β-cell injury is obscure. We investigated the role for JNK in streptozotocin (STZ)-induced β-cell death. STZ induced JNK activation in insulinoma or islet cells. JNK inhibitors attenuated insulinoma or islet cell death by STZ. STZ-induced JNK activation was decreased by PARP inhibitors, suggesting that JNK activation is downstream of PARP-1. Phosphatase inhibitors induced activation of JNK and abrogated the suppression of STZ-induced JNK activation by PARP inhibitors, suggesting that the inhibition of phosphatases is involved in the activation of JNK by STZ. STZ induced production of reactive oxygen species (ROS) as potential inhibitors of phosphatases, which was suppressed by PARP inhibitors. PARP-1 siRNA attenuated insulinoma cell death and JNK activation after STZ treatment, which was reversed by MKP (MAP kinase phosphatase)-1 siRNA. These results suggest that JNK is activated by STZ downstream of PARP-1 through inactivation of phosphatases such as MKP, which plays important roles in STZ-induced β-cell death.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Médecine
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 18127
- DOI 10.1016/j.mce.2010.02.016
- Persistent URL
- https://folia.unifr.ch/unifr/documents/301504
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