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Tat‐biliverdin reductase A protects INS‐1 cells from human islet amyloid polypeptide‐induced cytotoxicity by alleviating oxidative stress and ER stress
Author(s) -
Lee Su Jin,
Kang Hyung Kyung,
Eum Won Sik,
Park Jinseu,
Choi Soo Young,
Kwon Hyeok Yil
Publication year - 2017
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10750
Subject(s) - oxidative stress , unfolded protein response , biliverdin reductase , apoptosis , islet , microbiology and biotechnology , cytotoxicity , endoplasmic reticulum , programmed cell death , reactive oxygen species , amyloid (mycology) , endocrinology , medicine , chemistry , insulin , biology , biochemistry , heme oxygenase , heme , in vitro , inorganic chemistry , enzyme
Human islet amyloid polypeptide (hIAPP), a major constituent of islet amyloid deposits, induces pancreatic β‐cell apoptosis and eventually contributes to β‐cell deficit in patients with type 2 diabetes mellitus (T2DM). In this study, Tat‐mediated transduction of biliverdin reductase A (BLVRA) was investigated in INS‐1 cells to examine whether exogenous supplementation of BLVRA prevented hIAPP‐induced apoptosis and dysfunction in insulin secretion in β‐cells. Tat‐BLVRA fusion protein was efficiently delivered into INS‐1 cells in a time‐ and dose‐dependent manner. Exposure of cells to hIAPP induced apoptotic cell death, which was dose‐dependently inhibited by pre‐treatment with Tat‐BLVRA for 1 h. Transduced Tat‐BLVRA reduced hIAPP‐evoked generation of reactive oxygen species, a crucial mediator of β‐cell destruction. Immunoblot analysis showed that Tat‐BLVRA suppressed hIAPP‐induced increase in the levels of proteins involved in endoplasmic reticulum (ER) stress and apoptosis signaling. Transduced Tat‐BLVRA also recovered hIAPP‐induced dysfunction in basal and glucose‐stimulated insulin secretions. These results suggested that transduced Tat‐BLVRA enhanced the tolerance of β‐cells against IAPP‐induced cytotoxicity by alleviating oxidative stress and ER stress. Therefore, Tat‐mediated transduction of BLVRA may provide a potential tool to ameliorate β‐cell deficit in pancreas with T2DM.