The natural pesticide dihydrorotenone induces human plasma cell apoptosis by triggering endoplasmic reticulum stress and activating p38 signaling pathway.
Dihydrorotenone (DHR) is a natural pesticide widely used in farming industry, such as organic produces. DHR is a potent mitochondrial inhibitor and probably induces Parkinsonian syndrome, however, it is not known whether DHR is toxic to other systems. In the present study, we evaluated the cytotoxic...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2013-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3724796?pdf=render |
id |
doaj-b287a7d5d00d4e96a2b333cc94b0f62f |
---|---|
record_format |
Article |
spelling |
doaj-b287a7d5d00d4e96a2b333cc94b0f62f2020-11-25T02:47:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6991110.1371/journal.pone.0069911The natural pesticide dihydrorotenone induces human plasma cell apoptosis by triggering endoplasmic reticulum stress and activating p38 signaling pathway.Jieyu ZhangJuan TangBiyin CaoZubin ZhangJie LiAaron D SchimmerSudan HeXinliang MaoDihydrorotenone (DHR) is a natural pesticide widely used in farming industry, such as organic produces. DHR is a potent mitochondrial inhibitor and probably induces Parkinsonian syndrome, however, it is not known whether DHR is toxic to other systems. In the present study, we evaluated the cytotoxicity of DHR on human plasma cells. As predicted, DHR impaired mitochondrial function by decreasing mitochondrial membrane potential in plasma cells. Because mito-dysfunction leads to unfolded protein response (UPR) and endoplasmic reticulum (ER) stress, we examined the signature proteins in ER stress, including GRP78, ATF4, and CHOP. After DHR treatment, these proteins were significantly upregulated. It is reported that activation of the mitogen-activated protein kinases p38 and JNK are involved in endoplasmic reticulum stress. However, in the subsequent study, DHR was found to activate p38 but not the JNK signaling. When pre-treated with p38 inhibitor SB203580, activation of p38 and cell apoptosis induced by DHR was partially blocked. Thus, we found that DHR induced human plasma cell death by activating the p38 but not the JNK signaling pathway. Because plasma cells are very important in the immune system, this study provided a new insight in the safety evaluation of DHR application.http://europepmc.org/articles/PMC3724796?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jieyu Zhang Juan Tang Biyin Cao Zubin Zhang Jie Li Aaron D Schimmer Sudan He Xinliang Mao |
spellingShingle |
Jieyu Zhang Juan Tang Biyin Cao Zubin Zhang Jie Li Aaron D Schimmer Sudan He Xinliang Mao The natural pesticide dihydrorotenone induces human plasma cell apoptosis by triggering endoplasmic reticulum stress and activating p38 signaling pathway. PLoS ONE |
author_facet |
Jieyu Zhang Juan Tang Biyin Cao Zubin Zhang Jie Li Aaron D Schimmer Sudan He Xinliang Mao |
author_sort |
Jieyu Zhang |
title |
The natural pesticide dihydrorotenone induces human plasma cell apoptosis by triggering endoplasmic reticulum stress and activating p38 signaling pathway. |
title_short |
The natural pesticide dihydrorotenone induces human plasma cell apoptosis by triggering endoplasmic reticulum stress and activating p38 signaling pathway. |
title_full |
The natural pesticide dihydrorotenone induces human plasma cell apoptosis by triggering endoplasmic reticulum stress and activating p38 signaling pathway. |
title_fullStr |
The natural pesticide dihydrorotenone induces human plasma cell apoptosis by triggering endoplasmic reticulum stress and activating p38 signaling pathway. |
title_full_unstemmed |
The natural pesticide dihydrorotenone induces human plasma cell apoptosis by triggering endoplasmic reticulum stress and activating p38 signaling pathway. |
title_sort |
natural pesticide dihydrorotenone induces human plasma cell apoptosis by triggering endoplasmic reticulum stress and activating p38 signaling pathway. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Dihydrorotenone (DHR) is a natural pesticide widely used in farming industry, such as organic produces. DHR is a potent mitochondrial inhibitor and probably induces Parkinsonian syndrome, however, it is not known whether DHR is toxic to other systems. In the present study, we evaluated the cytotoxicity of DHR on human plasma cells. As predicted, DHR impaired mitochondrial function by decreasing mitochondrial membrane potential in plasma cells. Because mito-dysfunction leads to unfolded protein response (UPR) and endoplasmic reticulum (ER) stress, we examined the signature proteins in ER stress, including GRP78, ATF4, and CHOP. After DHR treatment, these proteins were significantly upregulated. It is reported that activation of the mitogen-activated protein kinases p38 and JNK are involved in endoplasmic reticulum stress. However, in the subsequent study, DHR was found to activate p38 but not the JNK signaling. When pre-treated with p38 inhibitor SB203580, activation of p38 and cell apoptosis induced by DHR was partially blocked. Thus, we found that DHR induced human plasma cell death by activating the p38 but not the JNK signaling pathway. Because plasma cells are very important in the immune system, this study provided a new insight in the safety evaluation of DHR application. |
url |
http://europepmc.org/articles/PMC3724796?pdf=render |
work_keys_str_mv |
AT jieyuzhang thenaturalpesticidedihydrorotenoneinduceshumanplasmacellapoptosisbytriggeringendoplasmicreticulumstressandactivatingp38signalingpathway AT juantang thenaturalpesticidedihydrorotenoneinduceshumanplasmacellapoptosisbytriggeringendoplasmicreticulumstressandactivatingp38signalingpathway AT biyincao thenaturalpesticidedihydrorotenoneinduceshumanplasmacellapoptosisbytriggeringendoplasmicreticulumstressandactivatingp38signalingpathway AT zubinzhang thenaturalpesticidedihydrorotenoneinduceshumanplasmacellapoptosisbytriggeringendoplasmicreticulumstressandactivatingp38signalingpathway AT jieli thenaturalpesticidedihydrorotenoneinduceshumanplasmacellapoptosisbytriggeringendoplasmicreticulumstressandactivatingp38signalingpathway AT aarondschimmer thenaturalpesticidedihydrorotenoneinduceshumanplasmacellapoptosisbytriggeringendoplasmicreticulumstressandactivatingp38signalingpathway AT sudanhe thenaturalpesticidedihydrorotenoneinduceshumanplasmacellapoptosisbytriggeringendoplasmicreticulumstressandactivatingp38signalingpathway AT xinliangmao thenaturalpesticidedihydrorotenoneinduceshumanplasmacellapoptosisbytriggeringendoplasmicreticulumstressandactivatingp38signalingpathway AT jieyuzhang naturalpesticidedihydrorotenoneinduceshumanplasmacellapoptosisbytriggeringendoplasmicreticulumstressandactivatingp38signalingpathway AT juantang naturalpesticidedihydrorotenoneinduceshumanplasmacellapoptosisbytriggeringendoplasmicreticulumstressandactivatingp38signalingpathway AT biyincao naturalpesticidedihydrorotenoneinduceshumanplasmacellapoptosisbytriggeringendoplasmicreticulumstressandactivatingp38signalingpathway AT zubinzhang naturalpesticidedihydrorotenoneinduceshumanplasmacellapoptosisbytriggeringendoplasmicreticulumstressandactivatingp38signalingpathway AT jieli naturalpesticidedihydrorotenoneinduceshumanplasmacellapoptosisbytriggeringendoplasmicreticulumstressandactivatingp38signalingpathway AT aarondschimmer naturalpesticidedihydrorotenoneinduceshumanplasmacellapoptosisbytriggeringendoplasmicreticulumstressandactivatingp38signalingpathway AT sudanhe naturalpesticidedihydrorotenoneinduceshumanplasmacellapoptosisbytriggeringendoplasmicreticulumstressandactivatingp38signalingpathway AT xinliangmao naturalpesticidedihydrorotenoneinduceshumanplasmacellapoptosisbytriggeringendoplasmicreticulumstressandactivatingp38signalingpathway |
_version_ |
1724751870422941696 |