The MAP kinase inhibitor PD98059 reduces chromosomal instability in the autoimmune encephalomyelitis SJL/J-mouse model of multiple sclerosis

Sabry M. Attia; Sheikh F. Ahmad; Ahmed Nadeem; Mohamed S.M. Attia; Mushtaq A. Ansari; Gamaleldin I. Harisa; Mohammed A. Al-Hamamah; Mohamed A. Mahmoud; Saleh A. Bakheet

doi:10.1016/j.mrgentox.2020.503278

The MAP kinase inhibitor PD98059 reduces chromosomal instability in the autoimmune encephalomyelitis SJL/J-mouse model of multiple sclerosis

Sabry M. Attia^*, Sheikh F. Ahmad, Ahmed Nadeem, Mohamed S.M. Attia, Mushtaq A. Ansari, Gamaleldin I. Harisa, Mohammed A. Al-Hamamah, Mohamed A. Mahmoud, Saleh A. Bakheet

^*Corresponding author for this work

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

6 Scopus citations

Abstract

Multiple sclerosis (MS), a disease in which the immune system attacks nerve cells, has been associated with both genetic and environmental risk factors. We observed increased micronucleus (MN) formation in SJL/J mouse experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Most of these MN were due to chromosomal loss. Increased activation of MAP kinases, which leads to disruption of the mitotic spindle and improper segregation of chromosomes, is associated with MS. MAP kinase inhibitors, such as PD98059, may therefore be beneficial for MS. In the EAE model, PD98059 treatment reduced adverse effects, including MN formation, lipid peroxidation, and GSH oxidation. Interventions that mitigate chromosomal instability may have therapeutic value in MS.

Original language	English
Article number	503278
Journal	Mutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume	861-862
DOIs	https://doi.org/10.1016/j.mrgentox.2020.503278
State	Published - 1 Jan 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2020 Elsevier B.V.

Keywords

Aneugenicity
Clastogenicity
Experimental autoimmune encephalomyelitis
Fluorescence in situ hybridization
Oxidative stress

ASJC Scopus subject areas

Genetics
Health, Toxicology and Mutagenesis

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10.1016/j.mrgentox.2020.503278

Cite this

Attia, S. M., Ahmad, S. F., Nadeem, A., Attia, M. S. M., Ansari, M. A., Harisa, G. I., Al-Hamamah, M. A., Mahmoud, M. A., & Bakheet, S. A. (2021). The MAP kinase inhibitor PD98059 reduces chromosomal instability in the autoimmune encephalomyelitis SJL/J-mouse model of multiple sclerosis. Mutation Research - Genetic Toxicology and Environmental Mutagenesis, 861-862, Article 503278. https://doi.org/10.1016/j.mrgentox.2020.503278

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title = "The MAP kinase inhibitor PD98059 reduces chromosomal instability in the autoimmune encephalomyelitis SJL/J-mouse model of multiple sclerosis",

abstract = "Multiple sclerosis (MS), a disease in which the immune system attacks nerve cells, has been associated with both genetic and environmental risk factors. We observed increased micronucleus (MN) formation in SJL/J mouse experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Most of these MN were due to chromosomal loss. Increased activation of MAP kinases, which leads to disruption of the mitotic spindle and improper segregation of chromosomes, is associated with MS. MAP kinase inhibitors, such as PD98059, may therefore be beneficial for MS. In the EAE model, PD98059 treatment reduced adverse effects, including MN formation, lipid peroxidation, and GSH oxidation. Interventions that mitigate chromosomal instability may have therapeutic value in MS.",

keywords = "Aneugenicity, Clastogenicity, Experimental autoimmune encephalomyelitis, Fluorescence in situ hybridization, Oxidative stress",

author = "Attia, {Sabry M.} and Ahmad, {Sheikh F.} and Ahmed Nadeem and Attia, {Mohamed S.M.} and Ansari, {Mushtaq A.} and Harisa, {Gamaleldin I.} and Al-Hamamah, {Mohammed A.} and Mahmoud, {Mohamed A.} and Bakheet, {Saleh A.}",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier B.V.",

year = "2021",

month = jan,

day = "1",

doi = "10.1016/j.mrgentox.2020.503278",

language = "English",

volume = "861-862",

journal = "Mutation Research - Genetic Toxicology and Environmental Mutagenesis",

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Attia, SM, Ahmad, SF, Nadeem, A, Attia, MSM, Ansari, MA, Harisa, GI, Al-Hamamah, MA, Mahmoud, MA & Bakheet, SA 2021, 'The MAP kinase inhibitor PD98059 reduces chromosomal instability in the autoimmune encephalomyelitis SJL/J-mouse model of multiple sclerosis', Mutation Research - Genetic Toxicology and Environmental Mutagenesis, vol. 861-862, 503278. https://doi.org/10.1016/j.mrgentox.2020.503278

The MAP kinase inhibitor PD98059 reduces chromosomal instability in the autoimmune encephalomyelitis SJL/J-mouse model of multiple sclerosis. / Attia, Sabry M.; Ahmad, Sheikh F.; Nadeem, Ahmed et al.
In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis, Vol. 861-862, 503278, 01.01.2021.

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

TY - JOUR

T1 - The MAP kinase inhibitor PD98059 reduces chromosomal instability in the autoimmune encephalomyelitis SJL/J-mouse model of multiple sclerosis

AU - Attia, Sabry M.

AU - Ahmad, Sheikh F.

AU - Nadeem, Ahmed

AU - Attia, Mohamed S.M.

AU - Ansari, Mushtaq A.

AU - Harisa, Gamaleldin I.

AU - Al-Hamamah, Mohammed A.

AU - Mahmoud, Mohamed A.

AU - Bakheet, Saleh A.

PY - 2021/1/1

Y1 - 2021/1/1

N2 - Multiple sclerosis (MS), a disease in which the immune system attacks nerve cells, has been associated with both genetic and environmental risk factors. We observed increased micronucleus (MN) formation in SJL/J mouse experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Most of these MN were due to chromosomal loss. Increased activation of MAP kinases, which leads to disruption of the mitotic spindle and improper segregation of chromosomes, is associated with MS. MAP kinase inhibitors, such as PD98059, may therefore be beneficial for MS. In the EAE model, PD98059 treatment reduced adverse effects, including MN formation, lipid peroxidation, and GSH oxidation. Interventions that mitigate chromosomal instability may have therapeutic value in MS.

AB - Multiple sclerosis (MS), a disease in which the immune system attacks nerve cells, has been associated with both genetic and environmental risk factors. We observed increased micronucleus (MN) formation in SJL/J mouse experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Most of these MN were due to chromosomal loss. Increased activation of MAP kinases, which leads to disruption of the mitotic spindle and improper segregation of chromosomes, is associated with MS. MAP kinase inhibitors, such as PD98059, may therefore be beneficial for MS. In the EAE model, PD98059 treatment reduced adverse effects, including MN formation, lipid peroxidation, and GSH oxidation. Interventions that mitigate chromosomal instability may have therapeutic value in MS.

KW - Aneugenicity

KW - Clastogenicity

KW - Experimental autoimmune encephalomyelitis

KW - Fluorescence in situ hybridization

KW - Oxidative stress

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SN - 1383-5718

VL - 861-862

JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis

JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis

M1 - 503278

ER -

The MAP kinase inhibitor PD98059 reduces chromosomal instability in the autoimmune encephalomyelitis SJL/J-mouse model of multiple sclerosis

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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