2011 Fiscal Year Final Research Report
The role of Keap1-Nrf2 system in oxidative stress response of pancreatic β-cells
| Project/Area Number |
22890014
|
|---|
| Research Category |
Grant-in-Aid for Research Activity Start-up
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
General medical chemistry
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
URUNO Akira 東北大学, 大学院・医学系研究科, 助教 (90396474)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
YAMAMOTO Masayuki 東北大学, 大学院・医学系研究科, 教授 (50166823)
|
|---|
| Project Period (FY) |
2010 – 2011
|
| Keywords | Keap1-Nrf2システム / 糖尿病 / 酸化ストレス |
|---|
| Research Abstract |
Nrf2 (NF-E2-related factor 2)is a basic region-leucine zipper-type transcription factor, which belongs to the Cap' n' collar family. Nrf2 is activated by various stresses including electrophiles, reactive oxygen species (ROS), reactive nitrogen species (RNS), and heavy metals, and coordinately induces anti-oxidant enzymes. Keap1 (Kelch-like ECH-associated protein 1)is an adaptor protein for Cullin3-base ubiquitin E3 ligase and acts as a sensor for stresses, which strictly regulates the Nrf2 activity.
We found that both Nrf2 and Keap1 are expressed in isolated islets from mice, and expression of Nrf2-target genes is upregulated by electrophiles, ROS and RNS. In addition, theβ-cell-damaged diabetes model mice crossed with Nrf2 hetero knockout showed elevated blood glucose levels and smaller islet size. Thus, these results support our contention that the Keap1-Nrf2 system plays important roles in the maintenance of pancreatic β-cells. The results further suggest that the Keap1-Nrf2 system may be involved in the pathogenesis of diabetes mellitus in stress conditions.
|
Research Products
(22 results)
-
[Journal Article] Accumulation of p62/SQSTM1 is associated with poor prognosis in patients with lung adenocarcinoma2012
Author(s)
Inoue D, Suzuki T, Mitsuishi Y, Miki Y, Suzuki S, Sugawara S, Watanabe M, Sakurada A, Endo C, Uruno A, Sasano H, Nakagawa T, Satoh K, Tanaka N, Kubo H, Motohashi H, Yamamoto M
-
Journal Title
Cancer Sci
Volume: 103(4)
Pages: 760-6
Peer Reviewed
-
-
[Journal Article] All-trans retinoic acid and a novel synthetic retinoid tamibarotene (Am80)differentially regulate CD38 expression in human leukemia HL-60 cells : possible involvement of protein kinase C-δ2011
Author(s)
Uruno A, Noguchi N, Matsuda K, Nata K, Yoshikawa T, Chikamatsu Y, Kagechika H, Harigae H, Ito S, Okamoto H, Sugawara A
-
Journal Title
J Leukoc Biol
Volume: 90(2)
Pages: 235-47
Peer Reviewed
-
[Journal Article] Peroxisome proliferator-activated receptor-γ suppresses CYP11B2 expression and aldosterone production2011
Author(s)
Uruno A, Matsuda K, Noguchi N, Yoshikawa T, Kudo M, Satoh F, Rainey WE, Hui XG, Akahira JI, Nakamura Y, Sasano H, Okamoto H, Ito S, Sugawara A
-
Journal Title
J Mol Endocrinol
Volume: 46(1)
Pages: 37-49
Peer Reviewed
-
-
-
[Journal Article] Up-regulation of REG Iα accelerates tumor progression in pancreatic cancer with diabetes2010
Author(s)
Zhou L, Zhang R, Wang L, Shen S, Okamoto H, Sugawara A, Xia L, Wang X, Noguchi N, Yoshikawa T, Uruno A, Yao W, Yuan Y
-
Journal Title
Int J Cancer
Volume: 127(8)
Pages: 1795-803
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
