The mammalian circadian clock gene Per2 modulates cell death in response to oxidative stress

Living in the earth’s oxygenated environment forced organisms to develop strategies to cope with the damaging effects of molecular oxygen known as reactive oxygen species (ROS). Here we show that Per2, a molecular component of the mammalian circadian clock, is involved in regulating a cell’s respons...

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Main Authors: Maria Chiara Magnone, Sonja eLangmesser, April Candice Bezdek, Tiziano eTallone, Sandro eRusconi, Urs eAlbrecht
Format: Article
Language:English
Published: Frontiers Media S.A. 2015-01-01
Series:Frontiers in Neurology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fneur.2014.00289/full
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author Maria Chiara Magnone
Sonja eLangmesser
April Candice Bezdek
Tiziano eTallone
Sandro eRusconi
Urs eAlbrecht
author_facet Maria Chiara Magnone
Sonja eLangmesser
April Candice Bezdek
Tiziano eTallone
Sandro eRusconi
Urs eAlbrecht
author_sort Maria Chiara Magnone
collection DOAJ
description Living in the earth’s oxygenated environment forced organisms to develop strategies to cope with the damaging effects of molecular oxygen known as reactive oxygen species (ROS). Here we show that Per2, a molecular component of the mammalian circadian clock, is involved in regulating a cell’s response to oxidative stress. Mouse embryonic fibroblasts (MEFs) containing a mutation in the Per2 gene are more resistant to cytotoxic effects mediated by ROS than wild type cells which is paralleled by an altered regulation of bcl-2 expression in Per2 mutant MEFs. The elevated survival rate and alteration of NADH/NAD+ ratio in the mutant cells is reversed by introduction of the wild type Per2 gene. Interestingly, clock synchronized cells display a time dependent sensitivity to paraquat, a ROS inducing agent. Our observations indicate that the circadian clock is involved in regulating the fate of a cell to survive or to die in response to oxidative stress, which could have implications for cancer development and the aging process.
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spelling doaj.art-5be31b4352794d61a1534b5f7e86acb42022-12-21T23:28:28ZengFrontiers Media S.A.Frontiers in Neurology1664-22952015-01-01510.3389/fneur.2014.00289127293The mammalian circadian clock gene Per2 modulates cell death in response to oxidative stressMaria Chiara Magnone0Sonja eLangmesser1April Candice Bezdek2Tiziano eTallone3Sandro eRusconi4Urs eAlbrecht5University of FribourgUniversity of FribourgUniversity of FribourgUniversity of FribourgUniversity of FribourgUniversity of FribourgLiving in the earth’s oxygenated environment forced organisms to develop strategies to cope with the damaging effects of molecular oxygen known as reactive oxygen species (ROS). Here we show that Per2, a molecular component of the mammalian circadian clock, is involved in regulating a cell’s response to oxidative stress. Mouse embryonic fibroblasts (MEFs) containing a mutation in the Per2 gene are more resistant to cytotoxic effects mediated by ROS than wild type cells which is paralleled by an altered regulation of bcl-2 expression in Per2 mutant MEFs. The elevated survival rate and alteration of NADH/NAD+ ratio in the mutant cells is reversed by introduction of the wild type Per2 gene. Interestingly, clock synchronized cells display a time dependent sensitivity to paraquat, a ROS inducing agent. Our observations indicate that the circadian clock is involved in regulating the fate of a cell to survive or to die in response to oxidative stress, which could have implications for cancer development and the aging process.http://journal.frontiersin.org/Journal/10.3389/fneur.2014.00289/fullApoptosisParaquatCircadian clockBcl-2adenovirusp53
spellingShingle Maria Chiara Magnone
Sonja eLangmesser
April Candice Bezdek
Tiziano eTallone
Sandro eRusconi
Urs eAlbrecht
The mammalian circadian clock gene Per2 modulates cell death in response to oxidative stress
Frontiers in Neurology
Apoptosis
Paraquat
Circadian clock
Bcl-2
adenovirus
p53
title The mammalian circadian clock gene Per2 modulates cell death in response to oxidative stress
title_full The mammalian circadian clock gene Per2 modulates cell death in response to oxidative stress
title_fullStr The mammalian circadian clock gene Per2 modulates cell death in response to oxidative stress
title_full_unstemmed The mammalian circadian clock gene Per2 modulates cell death in response to oxidative stress
title_short The mammalian circadian clock gene Per2 modulates cell death in response to oxidative stress
title_sort mammalian circadian clock gene per2 modulates cell death in response to oxidative stress
topic Apoptosis
Paraquat
Circadian clock
Bcl-2
adenovirus
p53
url http://journal.frontiersin.org/Journal/10.3389/fneur.2014.00289/full
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