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JNK1 Deficient Insulin-Producing Cells Are Protected against Interleukin-1β-Induced Apoptosis Associated with Abrogated Myc Expression

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@article{d56cc255a4c4459e800fbc02170167c0,
title = "JNK1 Deficient Insulin-Producing Cells Are Protected against Interleukin-1β-Induced Apoptosis Associated with Abrogated Myc Expression",
abstract = "The relative contributions of the JNK subtypes in inflammatory β-cell failure and apoptosis are unclear. The JNK protein family consists of JNK1, JNK2, and JNK3 subtypes, encompassing many different isoforms. INS-1 cells express JNK1α1, JNK1α2, JNK1β1, JNK1β2, JNK2α1, JNK2α2, JNK3α1, and JNK3α2 mRNA isoform transcripts translating into 46 and 54 kDa isoform JNK proteins. Utilizing Lentiviral mediated expression of shRNAs against JNK1, JNK2, or JNK3 in insulin-producing INS-1 cells, we investigated the role of individual JNK subtypes in IL-1β-induced β-cell apoptosis. JNK1 knockdown prevented IL-1β-induced INS-1 cell apoptosis associated with decreased 46 kDa isoform JNK protein phosphorylation and attenuated Myc expression. Transient knockdown of Myc also prevented IL-1β-induced apoptosis as well as caspase 3 cleavage. JNK2 shRNA potentiated IL-1β-induced apoptosis and caspase 3 cleavage, whereas JNK3 shRNA did not affect IL-1β-induced β-cell death compared to nonsense shRNA expressing INS-1 cells. In conclusion, JNK1 mediates INS-1 cell death associated with increased Myc expression. These findings underline the importance of differentiated targeting of JNK subtypes in the development of inflammatory β-cell failure and destruction.",
keywords = "Animals, Apoptosis, Caspase 3, Cell Line, Tumor, Insulin, Insulin-Secreting Cells, Interleukin-1beta, Mice, Mitogen-Activated Protein Kinase 10, Mitogen-Activated Protein Kinase 8, Mitogen-Activated Protein Kinase 9, Proto-Oncogene Proteins c-myc, RNA Interference, Rats, Signal Transduction, Time Factors, Transfection, Journal Article, Research Support, Non-U.S. Gov't",
author = "Michala Prause and Mayer, {Christopher Michael} and Caroline Brorsson and Frederiksen, {Klaus Stensgaard} and Nils Billestrup and Joachim St{\o}rling and Thomas Mandrup-Poulsen",
year = "2016",
doi = "10.1155/2016/1312705",
language = "English",
volume = "2016",
pages = "1312705",
journal = "Journal of Diabetes Research",
issn = "2314-6745",
publisher = "Hindawi Publishing Corporation",

}

RIS

TY - JOUR

T1 - JNK1 Deficient Insulin-Producing Cells Are Protected against Interleukin-1β-Induced Apoptosis Associated with Abrogated Myc Expression

AU - Prause, Michala

AU - Mayer, Christopher Michael

AU - Brorsson, Caroline

AU - Frederiksen, Klaus Stensgaard

AU - Billestrup, Nils

AU - Størling, Joachim

AU - Mandrup-Poulsen, Thomas

PY - 2016

Y1 - 2016

N2 - The relative contributions of the JNK subtypes in inflammatory β-cell failure and apoptosis are unclear. The JNK protein family consists of JNK1, JNK2, and JNK3 subtypes, encompassing many different isoforms. INS-1 cells express JNK1α1, JNK1α2, JNK1β1, JNK1β2, JNK2α1, JNK2α2, JNK3α1, and JNK3α2 mRNA isoform transcripts translating into 46 and 54 kDa isoform JNK proteins. Utilizing Lentiviral mediated expression of shRNAs against JNK1, JNK2, or JNK3 in insulin-producing INS-1 cells, we investigated the role of individual JNK subtypes in IL-1β-induced β-cell apoptosis. JNK1 knockdown prevented IL-1β-induced INS-1 cell apoptosis associated with decreased 46 kDa isoform JNK protein phosphorylation and attenuated Myc expression. Transient knockdown of Myc also prevented IL-1β-induced apoptosis as well as caspase 3 cleavage. JNK2 shRNA potentiated IL-1β-induced apoptosis and caspase 3 cleavage, whereas JNK3 shRNA did not affect IL-1β-induced β-cell death compared to nonsense shRNA expressing INS-1 cells. In conclusion, JNK1 mediates INS-1 cell death associated with increased Myc expression. These findings underline the importance of differentiated targeting of JNK subtypes in the development of inflammatory β-cell failure and destruction.

AB - The relative contributions of the JNK subtypes in inflammatory β-cell failure and apoptosis are unclear. The JNK protein family consists of JNK1, JNK2, and JNK3 subtypes, encompassing many different isoforms. INS-1 cells express JNK1α1, JNK1α2, JNK1β1, JNK1β2, JNK2α1, JNK2α2, JNK3α1, and JNK3α2 mRNA isoform transcripts translating into 46 and 54 kDa isoform JNK proteins. Utilizing Lentiviral mediated expression of shRNAs against JNK1, JNK2, or JNK3 in insulin-producing INS-1 cells, we investigated the role of individual JNK subtypes in IL-1β-induced β-cell apoptosis. JNK1 knockdown prevented IL-1β-induced INS-1 cell apoptosis associated with decreased 46 kDa isoform JNK protein phosphorylation and attenuated Myc expression. Transient knockdown of Myc also prevented IL-1β-induced apoptosis as well as caspase 3 cleavage. JNK2 shRNA potentiated IL-1β-induced apoptosis and caspase 3 cleavage, whereas JNK3 shRNA did not affect IL-1β-induced β-cell death compared to nonsense shRNA expressing INS-1 cells. In conclusion, JNK1 mediates INS-1 cell death associated with increased Myc expression. These findings underline the importance of differentiated targeting of JNK subtypes in the development of inflammatory β-cell failure and destruction.

KW - Animals

KW - Apoptosis

KW - Caspase 3

KW - Cell Line, Tumor

KW - Insulin

KW - Insulin-Secreting Cells

KW - Interleukin-1beta

KW - Mice

KW - Mitogen-Activated Protein Kinase 10

KW - Mitogen-Activated Protein Kinase 8

KW - Mitogen-Activated Protein Kinase 9

KW - Proto-Oncogene Proteins c-myc

KW - RNA Interference

KW - Rats

KW - Signal Transduction

KW - Time Factors

KW - Transfection

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1155/2016/1312705

DO - 10.1155/2016/1312705

M3 - Journal article

C2 - 26962537

VL - 2016

SP - 1312705

JO - Journal of Diabetes Research

JF - Journal of Diabetes Research

SN - 2314-6745

ER -

ID: 52804994