PMID- 23707560
OWN - NLM
STAT- MEDLINE
DCOM- 20130923
LR  - 20161126
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1832
IP  - 10
DP  - 2013 Oct
TI  - Global protein and histone arginine methylation are affected in a tissue-specific 
      manner in a rat model of diet-induced hyperhomocysteinemia.
PG  - 1708-14
LID - S0925-4439(13)00175-0 [pii]
LID - 10.1016/j.bbadis.2013.05.013 [doi]
AB  - Accumulation of S-adenosylhomocysteine (AdoHcy), the homocysteine (Hcy) precursor 
      and a potent methyltransferase inhibitor, may mediate the neurological and 
      vascular complications associated with elevated Hcy. Protein arginine methylation 
      is a crucial post-translational modification and generates monomethylarginine 
      (MMA) and dimethylarginine (asymmetric, ADMA, and symmetric, SDMA) residues. We 
      aimed at determining whether protein arginine methylation status is disturbed in 
      an animal model of diet-induced hyperhomocysteinemia (HHcy). HHcy was achieved by 
      dietary manipulation of Wistar rats: methionine-enrichment (HM), B vitamins 
      deficiency (LV), or both (HMLV). Total Hcy, S-adenosylmethionine (AdoMet), 
      AdoHcy, MMA, ADMA and SDMA concentrations in plasma or tissues (heart, brain and 
      liver) were determined by adequate high-performance liquid chromatography or 
      liquid chromatography-electrospray ionization-tandem mass spectrometry methods. 
      Moreover, in tissues from the HMLV group, histone arginine asymmetric 
      dimethylation was evaluated by Western blotting, and the histone methylation 
      marks H3R17me2a, H3R8me2a and H4R3me2a were studied. HHcy was induced by all 
      special diets, with elevation of AdoHcy concentrations in liver (LV and HMLV) and 
      heart (HMLV) (all versus control). Plasma ADMA levels were lower in all 
      hyperhomocysteinemic animals. Protein-incorporated ADMA levels were decreased in 
      brain and in heart (both for the LV and HMLV groups). Moreover, in brain of 
      animals exposed to the HMLV diet, the H3R8me2a mark was profoundly decreased. In 
      conclusion, our results show that diet-induced Hcy elevation disturbs global 
      protein arginine methylation in a tissue-specific manner and affects histone 
      arginine methylation in brain. Future research is warranted to disclose the 
      functional implications of the global protein and histone arginine 
      hypomethylation triggered by Hcy elevation.
CI  - Copyright (c) 2013 Elsevier B.V. All rights reserved.
FAU - Esse, Ruben
AU  - Esse R
AD  - Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The 
      Netherlands.
FAU - Florindo, Cristina
AU  - Florindo C
FAU - Imbard, Apolline
AU  - Imbard A
FAU - Rocha, Monica S
AU  - Rocha MS
FAU - de Vriese, An S
AU  - de Vriese AS
FAU - Smulders, Yvo M
AU  - Smulders YM
FAU - Teerlink, Tom
AU  - Teerlink T
FAU - Tavares de Almeida, Isabel
AU  - Tavares de Almeida I
FAU - Castro, Rita
AU  - Castro R
FAU - Blom, Henk J
AU  - Blom HJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130522
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Histones)
RN  - 0 (Proteins)
RN  - 94ZLA3W45F (Arginine)
SB  - IM
MH  - Animals
MH  - Arginine/*metabolism
MH  - *Diet
MH  - *Disease Models, Animal
MH  - Female
MH  - Histones/chemistry/*metabolism
MH  - Hyperhomocysteinemia/etiology/*metabolism
MH  - Methylation
MH  - Proteins/*metabolism
MH  - Rats
MH  - Rats, Wistar
OTO - NOTNLM
OT  - B vitamins deficiency
OT  - H3R8 methylation
OT  - Homocysteine
OT  - Protein methylation
OT  - S-adenosylhomocysteine
EDAT- 2013/05/28 06:00
MHDA- 2013/09/24 06:00
CRDT- 2013/05/28 06:00
PHST- 2012/12/10 00:00 [received]
PHST- 2013/05/08 00:00 [revised]
PHST- 2013/05/13 00:00 [accepted]
PHST- 2013/05/28 06:00 [entrez]
PHST- 2013/05/28 06:00 [pubmed]
PHST- 2013/09/24 06:00 [medline]
AID - S0925-4439(13)00175-0 [pii]
AID - 10.1016/j.bbadis.2013.05.013 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2013 Oct;1832(10):1708-14. doi: 
      10.1016/j.bbadis.2013.05.013. Epub 2013 May 22.