PMID- 25608649
OWN - NLM
STAT- MEDLINE
DCOM- 20150916
LR  - 20240322
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 16
IP  - 1
DP  - 2015 Jan 6
TI  - Mechanisms of hyperhomocysteinemia induced skeletal muscle myopathy after 
      ischemia in the CBS-/+ mouse model.
PG  - 1252-65
LID - 10.3390/ijms16011252 [doi]
AB  - Although hyperhomocysteinemia (HHcy) elicits lower than normal body weights and 
      skeletal muscle weakness, the mechanisms remain unclear. Despite the fact that 
      HHcy-mediated enhancement in ROS and consequent damage to regulators of different 
      cellular processes is relatively well established in other organs, the nature of 
      such events is unknown in skeletal muscles. Previously, we reported that HHcy 
      attenuation of PGC-1alpha and HIF-1alpha levels enhanced the likelihood of muscle atrophy 
      and declined function after ischemia. In the current study, we examined muscle 
      levels of homocysteine (Hcy) metabolizing enzymes, anti-oxidant capacity and 
      focused on protein modifications that might compromise PGC-1alpha function during 
      ischemic angiogenesis. Although skeletal muscles express the key enzyme (MTHFR) 
      that participates in re-methylation of Hcy into methionine, lack of 
      trans-sulfuration enzymes (CBS and CSE) make skeletal muscles more susceptible to 
      the HHcy-induced myopathy. Our study indicates that elevated Hcy levels in the 
      CBS-/+ mouse skeletal muscles caused diminished anti-oxidant capacity and 
      contributed to enhanced total protein as well as PGC-1alpha specific 
      nitrotyrosylation after ischemia. Furthermore, in the presence of NO donor SNP, 
      either homocysteine (Hcy) or its cyclized version, Hcy thiolactone, not only 
      increased PGC-1alpha specific protein nitrotyrosylation but also reduced its 
      association with PPARgamma in C2C12 cells. Altogether these results suggest that HHcy 
      exerts its myopathic effects via reduction of the PGC-1/PPARgamma axis after 
      ischemia.
FAU - Veeranki, Sudhakar
AU  - Veeranki S
AD  - Department of Physiology & Biophysics, University of Louisville, Louisville, KY 
      40202, USA. s0veer02@louisville.edu.
FAU - Tyagi, Suresh C
AU  - Tyagi SC
AD  - Department of Physiology & Biophysics, University of Louisville, Louisville, KY 
      40202, USA. s0tyag01@exchange.louisville.edu.
LA  - eng
GR  - R01 NS084823/NS/NINDS NIH HHS/United States
GR  - R01 HL074185/HL/NHLBI NIH HHS/United States
GR  - R01 HL108621/HL/NHLBI NIH HHS/United States
GR  - NS-84823/NS/NINDS NIH HHS/United States
GR  - HL-108621/HL/NHLBI NIH HHS/United States
GR  - HL-74185/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150106
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Antioxidants)
RN  - 0 (Nitric Oxide Donors)
RN  - 0 (PPAR gamma)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, mouse)
RN  - 0 (Transcription Factors)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 3604-79-3 (3-nitrotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
RN  - Homocysteinemia
SB  - IM
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Blotting, Western
MH  - Cystathionine beta-Synthase/*metabolism
MH  - Disease Models, Animal
MH  - Homocysteine/metabolism/pharmacology
MH  - Hyperhomocysteinemia/complications/enzymology/*pathology
MH  - Ischemia/complications/enzymology/*pathology
MH  - Mice, Inbred C57BL
MH  - Models, Biological
MH  - Muscle, Skeletal/*blood supply/drug effects/*pathology
MH  - Muscular Diseases/*enzymology/*pathology
MH  - Nitric Oxide Donors/pharmacology
MH  - PPAR gamma/metabolism
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
MH  - Protein Binding/drug effects
MH  - Transcription Factors/metabolism
MH  - Tyrosine/analogs & derivatives/metabolism
PMC - PMC4307302
EDAT- 2015/01/23 06:00
MHDA- 2015/09/17 06:00
PMCR- 2015/01/01
CRDT- 2015/01/23 06:00
PHST- 2014/11/12 00:00 [received]
PHST- 2014/12/30 00:00 [accepted]
PHST- 2015/01/23 06:00 [entrez]
PHST- 2015/01/23 06:00 [pubmed]
PHST- 2015/09/17 06:00 [medline]
PHST- 2015/01/01 00:00 [pmc-release]
AID - ijms16011252 [pii]
AID - ijms-16-01252 [pii]
AID - 10.3390/ijms16011252 [doi]
PST - epublish
SO  - Int J Mol Sci. 2015 Jan 6;16(1):1252-65. doi: 10.3390/ijms16011252.