Tat-DJ-1 inhibits oxidative stress-mediated RINm5F cell death through suppression of NF-κB and MAPK activation.
Oxidative stress is highly involved in the development of diabetes mellitus by destruction of pancreatic β-cells. DJ-1 is an antioxidant protein and DJ-1 expression levels are known to be reduced in diabetes mellitus. Thus, we examined the effects of DJ-1 protein against oxidative stress-induced pancreatic β-cell (RINm5F) death using cell permeable wild-type and mutant-type (C106A) Tat-DJ-1 proteins, which both efficiently transduced into RINm5F cells. Intracellular stability of wild-type Tat-DJ-1 persisted two times longer than C106A Tat-DJ-1. Wild-type Tat-DJ-1 protein markedly protected cells from hydrogen peroxide-induced toxicities such as cell death, reactive oxygen species generation, and DNA fragmentation. Further, wild-type Tat-DJ-1 protein significantly inhibited hydrogen peroxide-induced activation of mitogen-activated protein kinases and NF-κB signaling. On the other hand, C106A Tat-DJ-1 protein did not show the same protective effects. These results indicate that wild-type Tat-DJ-1 inhibits oxidative stress-induced cellular toxicity and activation of mitogen-activated protein kinases and NF-κB signals in RINm5F cells. These results suggest that wild-type Tat-DJ-1 protein may be a potential therapeutic agent against diabetes mellitus or toward the prevention of pancreatic β-cell destruction.
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252 Korea.
Hyo Sang
HS
Jo
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252 Korea.
Hyun Ju
HJ
Cha
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252 Korea.
Sang Jin
SJ
Kim
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252 Korea.
Hyeon Ji
HJ
Yeo
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252 Korea.
Su Bin
SB
Cho
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252 Korea.
Jung Hwan
JH
Park
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252 Korea.
Chi Hern
CH
Lee
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252 Korea.
Eun Ji
EJ
Yeo
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252 Korea.
Yeon Joo
YJ
Choi
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252 Korea.
Won Sik
WS
Eum
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252 Korea.
Soo Young
SY
Choi
Cytotoxicity; Mutant DJ-1; Oxidative stress; Protein therapy; WT Tat-DJ-1