PMID- 32799662
OWN - NLM
STAT- MEDLINE
DCOM- 20210920
LR  - 20221207
IS  - 1205-7541 (Electronic)
IS  - 0008-4212 (Linking)
VI  - 99
IP  - 1
DP  - 2021 Jan
TI  - High-methionine diet in skeletal muscle remodeling: epigenetic mechanism of 
      homocysteine-mediated growth retardation.
PG  - 56-63
LID - 10.1139/cjpp-2020-0093 [doi]
AB  - Epigenetic DNA methylation (1-carbon metabolism) is crucial for gene 
      imprinting/off-printing that ensures epigenetic memory but also generates a 
      copious amount of homocysteine (Hcy), unequivocally. That is why during 
      pregnancy, expectant mothers are recommended "folic acid" preemptively to avoid 
      birth defects in the young ones because of elevated Hcy levels (i.e., 
      hyperhomocysteinemia (HHcy)). As we know, children born with HHcy have several 
      musculoskeletal abnormalities, including growth retardation. Here, we focus on 
      the gut-dysbiotic microbiome implication(s) that we believe instigates the 
      "1-carbon metabolism" and HHcy causing growth retardation along with skeletal 
      muscle abnormalities. We test our hypothesis whether high-methionine diet (HMD) 
      (an amino acid that is high in red meat), a substrate for Hcy, can cause skeletal 
      muscle and growth retardation, and treatment with probiotics (PB) to mitigate 
      skeletal muscle dysfunction. To test this, we employed cystathionine beta-synthase, 
      CBS deficient mouse (CBS(+/-)) fed with/without HMD and with/without a probiotic 
      (Lactobacillus rhamnosus) in drinking water for 16 weeks. Matrix 
      metalloproteinase (MMP) activity, a hallmark of remodeling, was measured by 
      zymography. Muscle functions were scored via electric stimulation. Our results 
      suggest that compared to the wild-type, CBS(+/-) mice exhibited reduced growth 
      phenotype. MMP-2 activity was robust in CBS(+/-) and HMD effects were 
      successfully attenuated by PB intervention. Electrical stimulation magnitude was 
      decreased in CBS(+/-) and CBS(+/-) treated with HMD. Interestingly; PB mitigated 
      skeletal muscle growth retardation and atrophy. Collectively, results imply that 
      individuals with mild/moderate HHcy seem more prone to skeletal muscle injury and 
      its dysfunction.
FAU - Singh, Mahavir
AU  - Singh M
AD  - Department of Physiology, University of Louisville School of Medicine, 
      Louisville, KY 40202, USA.
FAU - George, Akash K
AU  - George AK
AD  - Department of Physiology, University of Louisville School of Medicine, 
      Louisville, KY 40202, USA.
FAU - Eyob, Wintana
AU  - Eyob W
AD  - College of Arts and Sciences, Case Western Reserve University, 10900 Euclid Ave., 
      Cleveland, OH 44106, USA.
FAU - Homme, Rubens P
AU  - Homme RP
AD  - Department of Physiology, University of Louisville School of Medicine, 
      Louisville, KY 40202, USA.
FAU - Stansic, Dragana
AU  - Stansic D
AD  - Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, 
      Kragujevac, Serbia.
FAU - Tyagi, Suresh C
AU  - Tyagi SC
AD  - Department of Physiology, University of Louisville School of Medicine, 
      Louisville, KY 40202, USA.
LA  - eng
PT  - Journal Article
DEP - 20200815
PL  - Canada
TA  - Can J Physiol Pharmacol
JT  - Canadian journal of physiology and pharmacology
JID - 0372712
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - AE28F7PNPL (Methionine)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.24 (Mmp2 protein, mouse)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
SB  - IM
MH  - Animals
MH  - Cystathionine beta-Synthase/deficiency/genetics
MH  - DNA Methylation
MH  - Disease Models, Animal
MH  - Dysbiosis/*complications/metabolism/microbiology/therapy
MH  - Epigenesis, Genetic
MH  - Female
MH  - Gastrointestinal Microbiome/physiology
MH  - Growth Disorders/blood/metabolism/pathology/*prevention & control
MH  - Homocysteine/blood/metabolism
MH  - Humans
MH  - Hyperhomocysteinemia/blood/*complications/genetics/metabolism
MH  - Lacticaseibacillus rhamnosus
MH  - Male
MH  - Matrix Metalloproteinase 2/genetics/metabolism
MH  - Methionine/administration & dosage/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Muscle, Skeletal/metabolism/*pathology
MH  - Probiotics/*administration & dosage
OTO - NOTNLM
OT  - 1-carbon metabolism
OT  - cystathionine beta-synthase
OT  - dysbiose
OT  - dysbiosis
OT  - metabolisme du carbone 1
OT  - oxyde de trimethylamine
OT  - phosphatidylethanolamine N-methyltransferase
OT  - phosphatidylethanolamine N-methyltransferase
OT  - trimethylamine oxide
EDAT- 2020/08/18 06:00
MHDA- 2021/09/21 06:00
CRDT- 2020/08/18 06:00
PHST- 2020/08/18 06:00 [pubmed]
PHST- 2021/09/21 06:00 [medline]
PHST- 2020/08/18 06:00 [entrez]
AID - 10.1139/cjpp-2020-0093 [doi]
PST - ppublish
SO  - Can J Physiol Pharmacol. 2021 Jan;99(1):56-63. doi: 10.1139/cjpp-2020-0093. Epub 
      2020 Aug 15.