PMID- 19730253
OWN - NLM
STAT- MEDLINE
DCOM- 20100115
LR  - 20131121
IS  - 1530-0293 (Electronic)
IS  - 0090-3493 (Linking)
VI  - 38
IP  - 1
DP  - 2010 Jan
TI  - Tumor necrosis factor-alpha decreases sarcoplasmic reticulum Ca2+-ATPase 
      expressions via the promoter methylation in cardiomyocytes.
PG  - 217-22
LID - 10.1097/CCM.0b013e3181b4a854 [doi]
AB  - OBJECTIVES: Sarcoplasmic reticulum Ca-ATPases (SERCA2a) plays an essential role 
      in the Ca homeostasis and cardiac functions. Tumor necrosis factor-alpha 
      (TNF-alpha) decreases the SERCA2a, which may underlie cardiac dysfunction during 
      sepsis and heart failure. Because the promoter region of SERCA2a contains CpG 
      islands, gene methylation should be critical in regulating SERCA2a. The present 
      study was to evaluate whether TNF-alpha can modulate SERCA2a via enhancing 
      methylation and to investigate the underlying mechanisms. DESIGN: Controlled 
      laboratory experiment. SETTING: University research laboratory. SUBJECTS: HL-1 
      cardiomyocytes. INTERVENTIONS: TNF-alpha (1-50 ng/mL) was administered in HL-1 
      cardiomyocytes with and without co-administration of an NF-kappaB inhibitor 
      (SN-50, 50 microg/mL), antioxidant agents (ascorbic acid, 100 microM, or coenzyme 
      Q10, 10 microM), or methylation inhibitor (5-aza-2'-deoxycytidine, 0.1, 1 
      microM). MEASUREMENTS AND MAIN RESULTS: TNF-alpha (50 ng/mL) decreased the 
      SERCA2a RNA and protein by quantitative polymerase chain reaction and immunoblot. 
      Furthermore, TNF-alpha (50 ng/mL) increased the methylation in the SERCA2a 
      promoter region, which was not influenced by the co-administration of SN-50, 
      ascorbic acid, or coenzyme Q10, but was attenuated by 5-aza-2'-deoxycytidine (0.1 
      microM). Additionally, TNF-alpha (50 ng/mL) increased the expression of DNA 
      methyltransferase 1. CONCLUSIONS: TNF-alpha increased DNA methyltransferase 
      levels, thus enhancing the methylation in the SERCA2a promoter region with a 
      result of reducing SERCA2a. These findings suggest that inhibition of 
      hypermethylation may be a novel treatment strategy for cardiac dysfunction.
FAU - Kao, Yu-Hsun
AU  - Kao YH
AD  - Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, 
      Taiwan.
FAU - Chen, Yao-Chang
AU  - Chen YC
FAU - Cheng, Chen-Chuan
AU  - Cheng CC
FAU - Lee, Ting-I
AU  - Lee TI
FAU - Chen, Yi-Jen
AU  - Chen YJ
FAU - Chen, Shih-Ann
AU  - Chen SA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Crit Care Med
JT  - Critical care medicine
JID - 0355501
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 63231-63-0 (RNA)
RN  - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
CIN - Crit Care Med. 2010 Jan;38(1):331-2. PMID: 20023489
MH  - Animals
MH  - Apoptosis/drug effects/genetics
MH  - Blotting, Northern
MH  - Calcium/*metabolism
MH  - Cells, Cultured
MH  - DNA Methylation
MH  - Gene Expression Regulation
MH  - Heart Atria/cytology
MH  - Mice
MH  - Myocytes, Cardiac/*metabolism
MH  - Oxidative Stress/drug effects
MH  - Promoter Regions, Genetic
MH  - RNA/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sarcoplasmic Reticulum Calcium-Transporting ATPases/drug 
      effects/genetics/*metabolism
MH  - Sensitivity and Specificity
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2009/09/05 06:00
MHDA- 2010/01/16 06:00
CRDT- 2009/09/05 06:00
PHST- 2009/09/05 06:00 [entrez]
PHST- 2009/09/05 06:00 [pubmed]
PHST- 2010/01/16 06:00 [medline]
AID - 10.1097/CCM.0b013e3181b4a854 [doi]
PST - ppublish
SO  - Crit Care Med. 2010 Jan;38(1):217-22. doi: 10.1097/CCM.0b013e3181b4a854.