PMID- 20798530
OWN - NLM
STAT- MEDLINE
DCOM- 20101208
LR  - 20190212
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 26
IP  - 3
DP  - 2010
TI  - Hyperhomocysteinemia is associated with decreased erythropoietin expression in 
      rats.
PG  - 449-56
LID - 10.1159/000320568 [doi]
AB  - BACKGROUND/AIMS: Elevated plasma homocysteine (Hcy) levels have been identified 
      as a pathogenic factor causing a variety of pathological changes in different 
      cells and tissues. In vertebrates, Hcy is produced solely from 
      S-adenosylhomocysteine (AdoHcy) through the catalysis of AdoHcy-hydrolase. The 
      direction of AdoHcy-hydrolase activity is determined by its cytosolic substrate 
      concentrations, thereby controlling intracellular AdoHcy levels. Most 
      S-adenosylmethionine (AdoMet)-dependent methyltransferases are regulated in vivo 
      by the ratio of AdoMet/AdoHcy, which is termed "methylation potential" (MP). To 
      test whether high rates of erythropoietin (EPO) expression is reduced by a low MP 
      in vivo we choosed the model of increased EPO production following carbon 
      monoxide (CO) exposure in rats in which high transcriptional activity is 
      responsible for renal EPO production. RESULTS: To induce a sustained 
      hyperhomocysteinemia in rats, we infused i.v. a low or high dose of Hcy resulting 
      in Hcy plasma levels of 87.4+/-6.2 and 300.8+/-23.7 mumol/l, respectively. Renal 
      tissue contents of AdoHcy, AdoMet, and adenosine (Ado) were measured after freeze 
      clamp by means of HPLC. Within 4h of CO exposure EPO serum levels increased from 
      13.6+/-0.4 (control) to 2254.8+/-278.3 mIU/ml. Only high dose of Hcy reduces 
      both, the MP from 40.8+/-2.0 to 8.2+/-1.0 in the kidney as well as EPO serum 
      levels by 40% compared to control rats. CONCLUSION: Our data show that severe 
      hyperhomocysteinemia (HHcy) affects the MP in the renal tissue and lowers EPO 
      expression following CO induced intoxication. This result supports the concept 
      that efficient EPO production requires an unimpaired MP.
CI  - Copyright 2010 S. Karger AG, Basel.
FAU - Grenz, Almut
AU  - Grenz A
AD  - Mucosal Inflammation Program, Department of Anesthesiology and Perioperative 
      Medicine, University of Colorado Health Sciences Center, Denver, USA.
FAU - Hermes, Marina
AU  - Hermes M
FAU - Hammel, Peter
AU  - Hammel P
FAU - Roll, Jan B
AU  - Roll JB
FAU - Osswald, Hartmut
AU  - Osswald H
FAU - Kloor, Doris
AU  - Kloor D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100824
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 11096-26-7 (Erythropoietin)
RN  - 7U1EE4V452 (Carbon Monoxide)
RN  - EC 3.3.1.1 (Adenosylhomocysteinase)
SB  - IM
MH  - Adenosylhomocysteinase/metabolism
MH  - Animals
MH  - Carbon Monoxide/toxicity
MH  - Erythropoietin/*blood
MH  - Homocysteine/blood
MH  - Hyperhomocysteinemia/chemically induced/*metabolism
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2010/08/28 06:00
MHDA- 2010/12/14 06:00
CRDT- 2010/08/28 06:00
PHST- 2010/07/02 00:00 [accepted]
PHST- 2010/08/28 06:00 [entrez]
PHST- 2010/08/28 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
AID - 000320568 [pii]
AID - 10.1159/000320568 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2010;26(3):449-56. doi: 10.1159/000320568. Epub 2010 Aug 
      24.