View in EDS

Obligatory Role of Early Ca2+ Responses in H2O2-Induced β-Cell Apoptosis

Saved in:
Bibliographic Details
Title: Obligatory Role of Early Ca2+ Responses in H2O2-Induced β-Cell Apoptosis
Authors: Sato, Taiji, Kaneko, Yukiko, Sawatani, Toshiaki, Noguchi, Akiko, Ishikawa, Tomohisa
Source: Biological & Pharmaceutical Bulletin. 38:1599-1605
Publisher Information: Pharmaceutical Society of Japan, 2015.
Publication Year: 2015
Subject Terms: Inositol 1,4,5-Trisphosphate Receptors -- antagonists & inhibitors -- metabolism, Insulin-Secreting Cells -- drug effects -- metabolism, Boron Compounds, 0301 basic medicine, 0303 health sciences, Cytochromes c -- metabolism, Cytochromes c, Apoptosis, Hydrogen Peroxide, Pharmacologie, 16. Peace & justice, Cell Line, Mitochondria, Rats, Apoptosis -- drug effects -- physiology, 03 medical and health sciences, Mitochondria -- metabolism, Insulin-Secreting Cells, Calcium -- metabolism, Animals, Inositol 1,4,5-Trisphosphate Receptors, Boron Compounds -- pharmacology, Calcium
Description: Our previous study using apoptosis analysis suggested that Ca(2+) release through inositol 1,4,5-trisphosphate (IP3) receptors and the subsequent Ca(2+) influx through store-operated channels (SOCs) constitute a triggering signal for H2O2-induced β-cell apoptosis. In the present study, we further examined the obligatory role of early Ca(2+) responses in β-cell apoptosis induction. H2O2 induced elevation of the cytosolic Ca(2+) concentration ([Ca(2+)]c) consisting of two phases: an initial transient [Ca(2+)]c elevation within 30 min and a slowly developing one thereafter. The first phase was almost abolished by 2-aminoethoxydiphenylborate (2-APB), which blocks IP3 receptors and cation channels including SOCs, while the second phase was only partially inhibited by 2-APB. The inhibition by 2-APB of the second phase was not observed when 2-APB was added 30 min after the treatment with H2O2. 2-APB also largely inhibited elevation of the mitochondrial Ca(2+) concentration ([Ca(2+)]m) induced by H2O2 when 2-APB was applied simultaneously with H2O2, but not when applied 30 min after H2O2 application. In addition, 2-APB inhibited the release of mitochondrial cytochrome c to the cytosol induced by H2O2 when 2-APB was applied simultaneously with H2O2 but not 30 min post-treatment. H2O2-induced [Ca(2+)]m elevation and cell death were not inhibited by Ru360, an inhibitor of the mitochondrial calcium uniporter (MCU). These results suggest that the H2O2-induced initial [Ca(2+)]c elevation, occurring within 30 min and mediated by Ca(2+) release through IP3 receptors and subsequent Ca(2+) influx through SOCs, leads to [Ca(2+)]m elevation, possibly through a mechanism independent of MCU, thereby inducing cytochrome c release and consequent apoptosis.
Document Type: Article
File Description: 2 full-text file(s): application/pdf; application/pdf
Language: English
ISSN: 1347-5215
0918-6158
DOI: 10.1248/bpb.b15-00396
Access URL: https://www.jstage.jst.go.jp/article/bpb/38/10/38_b15-00396/_pdf
https://pubmed.ncbi.nlm.nih.gov/26424020
https://pubmed.ncbi.nlm.nih.gov/26424020/
https://www.jstage.jst.go.jp/article/bpb/38/10/38_b15-00396/_article
https://www.jstage.jst.go.jp/article/bpb/38/10/38_b15-00396/_pdf
https://ci.nii.ac.jp/naid/130005101574
http://europepmc.org/abstract/MED/26424020
Accession Number: edsair.doi.dedup.....5e3d137095abf5427ca32e8aa0fe268c
Database: OpenAIRE
Description
Abstract:Our previous study using apoptosis analysis suggested that Ca(2+) release through inositol 1,4,5-trisphosphate (IP3) receptors and the subsequent Ca(2+) influx through store-operated channels (SOCs) constitute a triggering signal for H2O2-induced β-cell apoptosis. In the present study, we further examined the obligatory role of early Ca(2+) responses in β-cell apoptosis induction. H2O2 induced elevation of the cytosolic Ca(2+) concentration ([Ca(2+)]c) consisting of two phases: an initial transient [Ca(2+)]c elevation within 30 min and a slowly developing one thereafter. The first phase was almost abolished by 2-aminoethoxydiphenylborate (2-APB), which blocks IP3 receptors and cation channels including SOCs, while the second phase was only partially inhibited by 2-APB. The inhibition by 2-APB of the second phase was not observed when 2-APB was added 30 min after the treatment with H2O2. 2-APB also largely inhibited elevation of the mitochondrial Ca(2+) concentration ([Ca(2+)]m) induced by H2O2 when 2-APB was applied simultaneously with H2O2, but not when applied 30 min after H2O2 application. In addition, 2-APB inhibited the release of mitochondrial cytochrome c to the cytosol induced by H2O2 when 2-APB was applied simultaneously with H2O2 but not 30 min post-treatment. H2O2-induced [Ca(2+)]m elevation and cell death were not inhibited by Ru360, an inhibitor of the mitochondrial calcium uniporter (MCU). These results suggest that the H2O2-induced initial [Ca(2+)]c elevation, occurring within 30 min and mediated by Ca(2+) release through IP3 receptors and subsequent Ca(2+) influx through SOCs, leads to [Ca(2+)]m elevation, possibly through a mechanism independent of MCU, thereby inducing cytochrome c release and consequent apoptosis.
ISSN:13475215
09186158
DOI:10.1248/bpb.b15-00396