PMID- 28384716
OWN - NLM
STAT- MEDLINE
DCOM- 20170626
LR  - 20240325
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 58
IP  - 4
DP  - 2017 Apr 1
TI  - Analysis of MTHFR, CBS, Glutathione, Taurine, and Hydrogen Sulfide Levels in 
      Retinas of Hyperhomocysteinemic Mice.
PG  - 1954-1963
LID - 10.1167/iovs.16-21247 [doi]
AB  - PURPOSE: Hyperhomocysteinemia (Hhcy) is implicated in certain retinal 
      neurovascular diseases, although whether it is causative remains uncertain. In 
      isolated ganglion cells (GCs), mild Hhcy induces profound death, whereas retinal 
      phenotypes in Hhcy mice caused by mutations in remethylation (methylene 
      tetrahydrofolatereductase [Mthfr+/-]) or transsulfuration pathways (cystathionine 
      beta-synthase [Cbs+/-]) demonstrate mild GC loss and mild vasculopathy. The current 
      work investigated compensation in vivo of one pathway for the other, and, because 
      the transsulfuration pathway yields cysteine necessary for formation of 
      glutathione (GSH), taurine, and hydrogen sulfide (H2S), they were analyzed also. 
      METHODS: Retinas isolated from wild-type (WT), Mthfr+/-, and Cbs+/- mice (12 and 
      22 weeks) were analyzed for methylene tetrahydrofolate reductase (MTHFR), 
      cystathionine-beta-synthase (CBS), and cystathionase (CTH) RNA/protein levels. 
      Retinas were evaluated for levels of reduced:oxidized GSH (GSH:GSSG), Slc7a11 
      (xCT), taurine, taurine transporter (TAUT), and H2S. RESULTS: Aside from 
      decreased CBS RNA/protein levels in Cbs+/- retinas, there were minimal 
      alterations in remethylation/transsulfuration pathways in the two mutant mice 
      strains. Glutathione and taurine levels in Mthfr+/- and Cbs+/- retinas were 
      similar to WT, which may be due to robust levels of xCT and TAUT in mutant 
      retinas. Interestingly, levels of H2S were markedly increased in retinas of 
      Mthfr+/- and Cbs+/- mice compared with WT. CONCLUSIONS: Ganglion cell loss and 
      vasculopathy observed in Mthfr+/- and Cbs+/- mouse retinas may be milder than 
      expected, not because of compensatory increases of enzymes in 
      remethylation/transsulfuration pathways, but because downstream transsulfuration 
      pathway products GSH, taurine, and H2S are maintained at robust levels. Elevation 
      of H2S is particularly intriguing owing to neuroprotective properties reported 
      for this gasotransmitter.
FAU - Cui, Xuezhi
AU  - Cui X
AD  - Department of Cellular Biology and Anatomy, The Medical College of Georgia at 
      Augusta University, Augusta, Georgia, United States 2The James and Jean Culver 
      Vision Discovery Institute, Augusta University, Augusta, Georgia, United States.
FAU - Navneet, Soumya
AU  - Navneet S
AD  - Department of Cellular Biology and Anatomy, The Medical College of Georgia at 
      Augusta University, Augusta, Georgia, United States 2The James and Jean Culver 
      Vision Discovery Institute, Augusta University, Augusta, Georgia, United States.
FAU - Wang, Jing
AU  - Wang J
AD  - Department of Cellular Biology and Anatomy, The Medical College of Georgia at 
      Augusta University, Augusta, Georgia, United States 2The James and Jean Culver 
      Vision Discovery Institute, Augusta University, Augusta, Georgia, United States.
FAU - Roon, Penny
AU  - Roon P
AD  - Department of Cellular Biology and Anatomy, The Medical College of Georgia at 
      Augusta University, Augusta, Georgia, United States.
FAU - Chen, Wei
AU  - Chen W
AD  - Department of Chemistry, Washington State University, Pullman, Washington, United 
      States.
FAU - Xian, Ming
AU  - Xian M
AD  - Department of Chemistry, Washington State University, Pullman, Washington, United 
      States.
FAU - Smith, Sylvia B
AU  - Smith SB
AD  - Department of Cellular Biology and Anatomy, The Medical College of Georgia at 
      Augusta University, Augusta, Georgia, United States 2The James and Jean Culver 
      Vision Discovery Institute, Augusta University, Augusta, Georgia, United States 
      4Department of Ophthalmology, Augusta University, Augusta, Georgia, United 
      States.
LA  - eng
GR  - R01 EY012830/EY/NEI NIH HHS/United States
GR  - R01 HL116571/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 1EQV5MLY3D (Taurine)
RN  - 63231-63-0 (RNA)
RN  - EC 1.5.1.20 (MTHFR protein, mouse)
RN  - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
RN  - GAN16C9B8O (Glutathione)
RN  - YY9FVM7NSN (Hydrogen Sulfide)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - *Gene Expression Regulation
MH  - Glutathione/*metabolism
MH  - Hydrogen Sulfide/*metabolism
MH  - Hyperhomocysteinemia/complications/*genetics/metabolism
MH  - Methylenetetrahydrofolate Reductase (NADPH2)/biosynthesis/*genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - RNA/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Retina/metabolism/pathology
MH  - Retinal Diseases/etiology/genetics/metabolism
MH  - Retinal Ganglion Cells/*metabolism/pathology
MH  - Taurine/*metabolism
PMC - PMC5381329
EDAT- 2017/04/07 06:00
MHDA- 2017/06/27 06:00
PMCR- 2017/04/01
CRDT- 2017/04/07 06:00
PHST- 2017/04/07 06:00 [entrez]
PHST- 2017/04/07 06:00 [pubmed]
PHST- 2017/06/27 06:00 [medline]
PHST- 2017/04/01 00:00 [pmc-release]
AID - 2617096 [pii]
AID - IOVS-16-21247 [pii]
AID - 10.1167/iovs.16-21247 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2017 Apr 1;58(4):1954-1963. doi: 
      10.1167/iovs.16-21247.