The Rac2 GTPase contributes to cathepsin H-mediated protection against cytokine-induced apoptosis in insulin-secreting cells

Research output: Contribution to journal › Journal article › peer-review

Standard

The Rac2 GTPase contributes to cathepsin H-mediated protection against cytokine-induced apoptosis in insulin-secreting cells. / Floyel, Tina; Mirza, Aashiq Hussain; Kaur, Simranjeet; Frorup, Caroline; Yarani, Reza; Storling, Joachim; Pociot, Flemming.

In: Molecular and Cellular Endocrinology, Vol. 518, 110993, 2020.

Research output: Contribution to journal › Journal article › peer-review

Harvard

Floyel, T, Mirza, AH, Kaur, S, Frorup, C, Yarani, R, Storling, J & Pociot, F 2020, 'The Rac2 GTPase contributes to cathepsin H-mediated protection against cytokine-induced apoptosis in insulin-secreting cells', Molecular and Cellular Endocrinology, vol. 518, 110993. https://doi.org/10.1016/j.mce.2020.110993

APA

Floyel, T., Mirza, A. H., Kaur, S., Frorup, C., Yarani, R., Storling, J., & Pociot, F. (2020). The Rac2 GTPase contributes to cathepsin H-mediated protection against cytokine-induced apoptosis in insulin-secreting cells. Molecular and Cellular Endocrinology, 518, [110993]. https://doi.org/10.1016/j.mce.2020.110993

Vancouver

Floyel T, Mirza AH, Kaur S, Frorup C, Yarani R, Storling J et al. The Rac2 GTPase contributes to cathepsin H-mediated protection against cytokine-induced apoptosis in insulin-secreting cells. Molecular and Cellular Endocrinology. 2020;518. 110993. https://doi.org/10.1016/j.mce.2020.110993

Author

Floyel, Tina ; Mirza, Aashiq Hussain ; Kaur, Simranjeet ; Frorup, Caroline ; Yarani, Reza ; Storling, Joachim ; Pociot, Flemming. / The Rac2 GTPase contributes to cathepsin H-mediated protection against cytokine-induced apoptosis in insulin-secreting cells. In: Molecular and Cellular Endocrinology. 2020 ; Vol. 518.

Bibtex

@article{93047801437e4aec8066c7a199f1d235,
title = "The Rac2 GTPase contributes to cathepsin H-mediated protection against cytokine-induced apoptosis in insulin-secreting cells",
abstract = "The type 1 diabetes (T1D) risk locus on chromosome 15q25.1 harbors the candidate gene CTSH (cathepsin H). We previously demonstrated that CTSH regulates beta-cell function in vitro and in vivo. CTSH overexpression protected insulin-secreting INS-1 cells against cytokine-induced apoptosis. The purpose of the present study was to identify the genes through which CTSH mediates its protective effects. Micmarray analysis identified 63 annotated genes differentially expressed between CTSH-overexpressing INS-1 cells and control cells treated with interleukin-1 beta and interferon-gamma for up to 16h. Permutation test identified 10 significant genes across all timepoints: Elmod1, Fam49a, Gas7, Gnal5, Msrb3, Nox1, Ptgs1, Rac2, Scn7a and Ttn. Pathway analysis identified the {"}Inflammation mediated by chemokine and cytokine signaling pathway{"} with Gnal5, Ptgs1 and Rac2 as significant. Knockdown of Rac2 abolished the protective effect of CTSH overexpression on cytokine-induced apoptosis, suggesting that the small GTPase and T1D candidate gene Rac2 contributes to the anti-apoptotic effect of CTSH.",
keywords = "Type 1 diabetes, Beta cell, Inflammation, Cell death, CTSH, Microarray, GENOME-WIDE ASSOCIATION, HUMAN PANCREATIC-ISLETS, CANDIDATE GENES, NITRIC-OXIDE, REACTIVE OXYGEN, EXPRESSION, CYCLOOXYGENASE-2, INFLAMMATION, ACTIVATION, PATHOGENESIS",
author = "Tina Floyel and Mirza, {Aashiq Hussain} and Simranjeet Kaur and Caroline Frorup and Reza Yarani and Joachim Storling and Flemming Pociot",
year = "2020",
doi = "10.1016/j.mce.2020.110993",
language = "English",
volume = "518",
journal = "Molecular and Cellular Endocrinology",
issn = "0303-7207",
publisher = "Elsevier Ireland Ltd",

}

RIS

TY - JOUR

T1 - The Rac2 GTPase contributes to cathepsin H-mediated protection against cytokine-induced apoptosis in insulin-secreting cells

AU - Floyel, Tina

AU - Mirza, Aashiq Hussain

AU - Kaur, Simranjeet

AU - Frorup, Caroline

AU - Yarani, Reza

AU - Storling, Joachim

AU - Pociot, Flemming

PY - 2020

Y1 - 2020

N2 - The type 1 diabetes (T1D) risk locus on chromosome 15q25.1 harbors the candidate gene CTSH (cathepsin H). We previously demonstrated that CTSH regulates beta-cell function in vitro and in vivo. CTSH overexpression protected insulin-secreting INS-1 cells against cytokine-induced apoptosis. The purpose of the present study was to identify the genes through which CTSH mediates its protective effects. Micmarray analysis identified 63 annotated genes differentially expressed between CTSH-overexpressing INS-1 cells and control cells treated with interleukin-1 beta and interferon-gamma for up to 16h. Permutation test identified 10 significant genes across all timepoints: Elmod1, Fam49a, Gas7, Gnal5, Msrb3, Nox1, Ptgs1, Rac2, Scn7a and Ttn. Pathway analysis identified the "Inflammation mediated by chemokine and cytokine signaling pathway" with Gnal5, Ptgs1 and Rac2 as significant. Knockdown of Rac2 abolished the protective effect of CTSH overexpression on cytokine-induced apoptosis, suggesting that the small GTPase and T1D candidate gene Rac2 contributes to the anti-apoptotic effect of CTSH.

AB - The type 1 diabetes (T1D) risk locus on chromosome 15q25.1 harbors the candidate gene CTSH (cathepsin H). We previously demonstrated that CTSH regulates beta-cell function in vitro and in vivo. CTSH overexpression protected insulin-secreting INS-1 cells against cytokine-induced apoptosis. The purpose of the present study was to identify the genes through which CTSH mediates its protective effects. Micmarray analysis identified 63 annotated genes differentially expressed between CTSH-overexpressing INS-1 cells and control cells treated with interleukin-1 beta and interferon-gamma for up to 16h. Permutation test identified 10 significant genes across all timepoints: Elmod1, Fam49a, Gas7, Gnal5, Msrb3, Nox1, Ptgs1, Rac2, Scn7a and Ttn. Pathway analysis identified the "Inflammation mediated by chemokine and cytokine signaling pathway" with Gnal5, Ptgs1 and Rac2 as significant. Knockdown of Rac2 abolished the protective effect of CTSH overexpression on cytokine-induced apoptosis, suggesting that the small GTPase and T1D candidate gene Rac2 contributes to the anti-apoptotic effect of CTSH.

KW - Type 1 diabetes

KW - Beta cell

KW - Inflammation

KW - Cell death

KW - CTSH

KW - Microarray

KW - GENOME-WIDE ASSOCIATION

KW - HUMAN PANCREATIC-ISLETS

KW - CANDIDATE GENES

KW - NITRIC-OXIDE

KW - REACTIVE OXYGEN

KW - EXPRESSION

KW - CYCLOOXYGENASE-2

KW - INFLAMMATION

KW - ACTIVATION

KW - PATHOGENESIS

U2 - 10.1016/j.mce.2020.110993

DO - 10.1016/j.mce.2020.110993

M3 - Journal article

C2 - 32814070

VL - 518

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

M1 - 110993

ER -

ID: 256986062