Flavin-containing monooxygenase mRNA levels are up-regulated in ALS brain areas in SOD1-mutant mice

Stella Gagliardi, Paolo Ogliari, Annalisa Davin, Manuel Corato, Emanuela Cova, Kenneth Abel, John R. Cashman, Mauro Ceroni, Cristina Cereda

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Flavin-containing monooxygenases (FMOs) are a family of microsomal enzymes involved in the oxygenation of a variety of nucleophilic heteroatom-containing xenobiotics. Recent results have pointed to a relation between Amyotrophic Lateral Sclerosis (ALS) and FMO genes. ALS is an adult-onset, progressive, and fatal neurodegenerative disease. We have compared FMO mRNA expression in the control mouse strain C57BL/6J and in a SOD1-mutated (G93A) ALS mouse model. Fmo expression was examined in total brain, and in subregions including cerebellum, cerebral hemisphere, brainstem, and spinal cord of control and SOD1-mutated mice. We have also considered expression in male and female mice because FMO regulation is gender-related. Real-Time TaqMan PCR was used for FMO expression analysis. Normalization was done using hypoxanthine-guanine phosphoribosyl transferase (Hprt) as a control housekeeping gene. Fmo genes, except Fmo3, were detectably expressed in the central nervous system of both control and ALS model mice. FMO expression was generally greater in the ALS mouse model than in control mice, with the highest increase in Fmo1 expression in spinal cord and brainstem. In addition, we showed greater Fmo expression in males than in female mice in the ALS model. The expression of Fmo1 mRNA correlated with Sod1 mRNA expression in pathologic brain areas. We hypothesize that alteration of FMO gene expression is a consequence of the pathological environment linked to oxidative stress related to mutated SOD1.

Original languageEnglish
Pages (from-to)150-158
Number of pages9
JournalNeurotoxicity Research
Volume20
Issue number2
DOIs
Publication statusPublished - Aug 2011

Fingerprint

dimethylaniline monooxygenase (N-oxide forming)
Amyotrophic Lateral Sclerosis
Brain
Messenger RNA
Genes
Brain Stem
Spinal Cord
Neurodegenerative diseases
Hypoxanthine
Oxidative stress
Oxygenation
Essential Genes
Guanine
Cerebrum
Neurology
Xenobiotics
Transferases
Inbred C57BL Mouse
Gene expression
Neurodegenerative Diseases

Keywords

  • Amyotrophic lateral sclerosis
  • Exposure to toxins
  • FMO
  • qPCR
  • SOD1

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Flavin-containing monooxygenase mRNA levels are up-regulated in ALS brain areas in SOD1-mutant mice. / Gagliardi, Stella; Ogliari, Paolo; Davin, Annalisa; Corato, Manuel; Cova, Emanuela; Abel, Kenneth; Cashman, John R.; Ceroni, Mauro; Cereda, Cristina.

In: Neurotoxicity Research, Vol. 20, No. 2, 08.2011, p. 150-158.

Research output: Contribution to journalArticle

Gagliardi, Stella ; Ogliari, Paolo ; Davin, Annalisa ; Corato, Manuel ; Cova, Emanuela ; Abel, Kenneth ; Cashman, John R. ; Ceroni, Mauro ; Cereda, Cristina. / Flavin-containing monooxygenase mRNA levels are up-regulated in ALS brain areas in SOD1-mutant mice. In: Neurotoxicity Research. 2011 ; Vol. 20, No. 2. pp. 150-158.
@article{20f10d25d7e74cb1bf2a6ee6ada914fa,
title = "Flavin-containing monooxygenase mRNA levels are up-regulated in ALS brain areas in SOD1-mutant mice",
abstract = "Flavin-containing monooxygenases (FMOs) are a family of microsomal enzymes involved in the oxygenation of a variety of nucleophilic heteroatom-containing xenobiotics. Recent results have pointed to a relation between Amyotrophic Lateral Sclerosis (ALS) and FMO genes. ALS is an adult-onset, progressive, and fatal neurodegenerative disease. We have compared FMO mRNA expression in the control mouse strain C57BL/6J and in a SOD1-mutated (G93A) ALS mouse model. Fmo expression was examined in total brain, and in subregions including cerebellum, cerebral hemisphere, brainstem, and spinal cord of control and SOD1-mutated mice. We have also considered expression in male and female mice because FMO regulation is gender-related. Real-Time TaqMan PCR was used for FMO expression analysis. Normalization was done using hypoxanthine-guanine phosphoribosyl transferase (Hprt) as a control housekeeping gene. Fmo genes, except Fmo3, were detectably expressed in the central nervous system of both control and ALS model mice. FMO expression was generally greater in the ALS mouse model than in control mice, with the highest increase in Fmo1 expression in spinal cord and brainstem. In addition, we showed greater Fmo expression in males than in female mice in the ALS model. The expression of Fmo1 mRNA correlated with Sod1 mRNA expression in pathologic brain areas. We hypothesize that alteration of FMO gene expression is a consequence of the pathological environment linked to oxidative stress related to mutated SOD1.",
keywords = "Amyotrophic lateral sclerosis, Exposure to toxins, FMO, qPCR, SOD1",
author = "Stella Gagliardi and Paolo Ogliari and Annalisa Davin and Manuel Corato and Emanuela Cova and Kenneth Abel and Cashman, {John R.} and Mauro Ceroni and Cristina Cereda",
year = "2011",
month = "8",
doi = "10.1007/s12640-010-9230-y",
language = "English",
volume = "20",
pages = "150--158",
journal = "Neurotoxicity Research",
issn = "1029-8428",
publisher = "Springer New York",
number = "2",

}

TY - JOUR

T1 - Flavin-containing monooxygenase mRNA levels are up-regulated in ALS brain areas in SOD1-mutant mice

AU - Gagliardi, Stella

AU - Ogliari, Paolo

AU - Davin, Annalisa

AU - Corato, Manuel

AU - Cova, Emanuela

AU - Abel, Kenneth

AU - Cashman, John R.

AU - Ceroni, Mauro

AU - Cereda, Cristina

PY - 2011/8

Y1 - 2011/8

N2 - Flavin-containing monooxygenases (FMOs) are a family of microsomal enzymes involved in the oxygenation of a variety of nucleophilic heteroatom-containing xenobiotics. Recent results have pointed to a relation between Amyotrophic Lateral Sclerosis (ALS) and FMO genes. ALS is an adult-onset, progressive, and fatal neurodegenerative disease. We have compared FMO mRNA expression in the control mouse strain C57BL/6J and in a SOD1-mutated (G93A) ALS mouse model. Fmo expression was examined in total brain, and in subregions including cerebellum, cerebral hemisphere, brainstem, and spinal cord of control and SOD1-mutated mice. We have also considered expression in male and female mice because FMO regulation is gender-related. Real-Time TaqMan PCR was used for FMO expression analysis. Normalization was done using hypoxanthine-guanine phosphoribosyl transferase (Hprt) as a control housekeeping gene. Fmo genes, except Fmo3, were detectably expressed in the central nervous system of both control and ALS model mice. FMO expression was generally greater in the ALS mouse model than in control mice, with the highest increase in Fmo1 expression in spinal cord and brainstem. In addition, we showed greater Fmo expression in males than in female mice in the ALS model. The expression of Fmo1 mRNA correlated with Sod1 mRNA expression in pathologic brain areas. We hypothesize that alteration of FMO gene expression is a consequence of the pathological environment linked to oxidative stress related to mutated SOD1.

AB - Flavin-containing monooxygenases (FMOs) are a family of microsomal enzymes involved in the oxygenation of a variety of nucleophilic heteroatom-containing xenobiotics. Recent results have pointed to a relation between Amyotrophic Lateral Sclerosis (ALS) and FMO genes. ALS is an adult-onset, progressive, and fatal neurodegenerative disease. We have compared FMO mRNA expression in the control mouse strain C57BL/6J and in a SOD1-mutated (G93A) ALS mouse model. Fmo expression was examined in total brain, and in subregions including cerebellum, cerebral hemisphere, brainstem, and spinal cord of control and SOD1-mutated mice. We have also considered expression in male and female mice because FMO regulation is gender-related. Real-Time TaqMan PCR was used for FMO expression analysis. Normalization was done using hypoxanthine-guanine phosphoribosyl transferase (Hprt) as a control housekeeping gene. Fmo genes, except Fmo3, were detectably expressed in the central nervous system of both control and ALS model mice. FMO expression was generally greater in the ALS mouse model than in control mice, with the highest increase in Fmo1 expression in spinal cord and brainstem. In addition, we showed greater Fmo expression in males than in female mice in the ALS model. The expression of Fmo1 mRNA correlated with Sod1 mRNA expression in pathologic brain areas. We hypothesize that alteration of FMO gene expression is a consequence of the pathological environment linked to oxidative stress related to mutated SOD1.

KW - Amyotrophic lateral sclerosis

KW - Exposure to toxins

KW - FMO

KW - qPCR

KW - SOD1

UR - http://www.scopus.com/inward/record.url?scp=80052623000&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052623000&partnerID=8YFLogxK

U2 - 10.1007/s12640-010-9230-y

DO - 10.1007/s12640-010-9230-y

M3 - Article

C2 - 21082301

AN - SCOPUS:80052623000

VL - 20

SP - 150

EP - 158

JO - Neurotoxicity Research

JF - Neurotoxicity Research

SN - 1029-8428

IS - 2

ER -