CIIA prevents SOD1(G93A)-induced cytotoxicity by blocking ASK1-mediated signaling

Jae Keun Lee; Sang Gil Hwang; Jin Hee Shin; Jaekyung Shim; Eui Ju Choi

doi:10.3389/fncel.2014.00179

CIIA prevents SOD1(G93A)-induced cytotoxicity by blocking ASK1-mediated signaling

Jae Keun Lee, Sang Gil Hwang, Jin Hee Shin, Jaekyung Shim, Eui Ju Choi

Department of Life Sciences

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease with higher selectivity in degeneration of motor neurons. However, the molecular mechanism by which the ALS-linked mutants of human superoxide dismutase 1 (SOD1) gene induce neurotoxicity remains obscure yet. Here, we show that depletion of CIIA expression by RNA interference (RNAi) promoted cytotoxicity caused by ALS-linked G93A mutant of the SOD1 gene. The RNAi-mediated knockdown of CIIA also enhanced the SOD1(G93A)-induced interaction between ASK1 and TRAF2 as well as ASK1 activity. Furthermore, endogenous silencing of CIIA by RNAi augmented the effects of SOD1(G93A) on reduction of mitochondria membrane potential (Δψ_m), release of cytochrome c into the cytoplasm, and caspase activation. Together, our results suggest that CIIA negatively modulates ASK1-mediated cytotoxic signaling processes in a SOD1(G93A)-expressing cellular model of ALS.

Original language	English
Article number	179
Journal	Frontiers in Cellular Neuroscience
Volume	8
Issue number	JUN
DOIs	https://doi.org/10.3389/fncel.2014.00179
Publication status	Published - 2014

Keywords

ALS (amyotrophic lateral sclerosis)
ASK1 (apoptosis signal-regulating kinase 1)
Cytotoxicity
Mitochondria
ROS (reactive oxygen species)

ASJC Scopus subject areas

Cellular and Molecular Neuroscience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3389/fncel.2014.00179

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@article{efa93ac79cb74f73a157287a0d2b8695,

title = "CIIA prevents SOD1(G93A)-induced cytotoxicity by blocking ASK1-mediated signaling",

abstract = "Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease with higher selectivity in degeneration of motor neurons. However, the molecular mechanism by which the ALS-linked mutants of human superoxide dismutase 1 (SOD1) gene induce neurotoxicity remains obscure yet. Here, we show that depletion of CIIA expression by RNA interference (RNAi) promoted cytotoxicity caused by ALS-linked G93A mutant of the SOD1 gene. The RNAi-mediated knockdown of CIIA also enhanced the SOD1(G93A)-induced interaction between ASK1 and TRAF2 as well as ASK1 activity. Furthermore, endogenous silencing of CIIA by RNAi augmented the effects of SOD1(G93A) on reduction of mitochondria membrane potential (Δψm), release of cytochrome c into the cytoplasm, and caspase activation. Together, our results suggest that CIIA negatively modulates ASK1-mediated cytotoxic signaling processes in a SOD1(G93A)-expressing cellular model of ALS.",

keywords = "ALS (amyotrophic lateral sclerosis), ASK1 (apoptosis signal-regulating kinase 1), Cytotoxicity, Mitochondria, ROS (reactive oxygen species)",

author = "Lee, {Jae Keun} and Hwang, {Sang Gil} and Shin, {Jin Hee} and Jaekyung Shim and Choi, {Eui Ju}",

year = "2014",

doi = "10.3389/fncel.2014.00179",

language = "English",

volume = "8",

journal = "Frontiers in Cellular Neuroscience",

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publisher = "Frontiers Research Foundation",

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T1 - CIIA prevents SOD1(G93A)-induced cytotoxicity by blocking ASK1-mediated signaling

AU - Lee, Jae Keun

AU - Hwang, Sang Gil

AU - Shin, Jin Hee

AU - Shim, Jaekyung

AU - Choi, Eui Ju

PY - 2014

Y1 - 2014

N2 - Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease with higher selectivity in degeneration of motor neurons. However, the molecular mechanism by which the ALS-linked mutants of human superoxide dismutase 1 (SOD1) gene induce neurotoxicity remains obscure yet. Here, we show that depletion of CIIA expression by RNA interference (RNAi) promoted cytotoxicity caused by ALS-linked G93A mutant of the SOD1 gene. The RNAi-mediated knockdown of CIIA also enhanced the SOD1(G93A)-induced interaction between ASK1 and TRAF2 as well as ASK1 activity. Furthermore, endogenous silencing of CIIA by RNAi augmented the effects of SOD1(G93A) on reduction of mitochondria membrane potential (Δψm), release of cytochrome c into the cytoplasm, and caspase activation. Together, our results suggest that CIIA negatively modulates ASK1-mediated cytotoxic signaling processes in a SOD1(G93A)-expressing cellular model of ALS.

AB - Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease with higher selectivity in degeneration of motor neurons. However, the molecular mechanism by which the ALS-linked mutants of human superoxide dismutase 1 (SOD1) gene induce neurotoxicity remains obscure yet. Here, we show that depletion of CIIA expression by RNA interference (RNAi) promoted cytotoxicity caused by ALS-linked G93A mutant of the SOD1 gene. The RNAi-mediated knockdown of CIIA also enhanced the SOD1(G93A)-induced interaction between ASK1 and TRAF2 as well as ASK1 activity. Furthermore, endogenous silencing of CIIA by RNAi augmented the effects of SOD1(G93A) on reduction of mitochondria membrane potential (Δψm), release of cytochrome c into the cytoplasm, and caspase activation. Together, our results suggest that CIIA negatively modulates ASK1-mediated cytotoxic signaling processes in a SOD1(G93A)-expressing cellular model of ALS.

KW - ALS (amyotrophic lateral sclerosis)

KW - ASK1 (apoptosis signal-regulating kinase 1)

KW - Cytotoxicity

KW - Mitochondria

KW - ROS (reactive oxygen species)

UR - http://www.scopus.com/inward/record.url?scp=84903398571&partnerID=8YFLogxK

U2 - 10.3389/fncel.2014.00179

DO - 10.3389/fncel.2014.00179

M3 - Article

AN - SCOPUS:84903398571

SN - 1662-5102

VL - 8

JO - Frontiers in Cellular Neuroscience

JF - Frontiers in Cellular Neuroscience

IS - JUN

M1 - 179

ER -

CIIA prevents SOD1(G93A)-induced cytotoxicity by blocking ASK1-mediated signaling

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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