JNK1 Deficient Insulin-Producing Cells Are Protected against Interleukin-1 beta-Induced Apoptosis Associated with Abrogated Myc Expression
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JNK1 Deficient Insulin-Producing Cells Are Protected against Interleukin-1 beta-Induced Apoptosis Associated with Abrogated Myc Expression. / Prause, Michala; Mayer, Christopher Michael; Brorsson, Caroline; Frederiksen, Klaus Stensgaard; Billestrup, Nils; Storling, Joachim; Mandrup-Poulsen, Thomas.
In: Journal of Diabetes Research, Vol. 2016, 1312705, 2016.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - JNK1 Deficient Insulin-Producing Cells Are Protected against Interleukin-1 beta-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 - Storling, 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.
U2 - 10.1155/2016/1312705
DO - 10.1155/2016/1312705
M3 - Journal article
C2 - 26962537
VL - 2016
JO - Journal of Diabetes Research
JF - Journal of Diabetes Research
SN - 2314-6745
M1 - 1312705
ER -
ID: 164621097