PMID- 27591219
OWN - NLM
STAT- MEDLINE
DCOM- 20170626
LR  - 20200930
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Linking)
VI  - 311
IP  - 4
DP  - 2016 Oct 1
TI  - Resveratrol protects against lipopolysaccharide-induced cardiac dysfunction by 
      enhancing SERCA2a activity through promoting the phospholamban oligomerization.
PG  - H1051-H1062
LID - 10.1152/ajpheart.00296.2016 [doi]
AB  - The bacterial endotoxin lipopolysaccharide (LPS) is a main culprit responsible 
      for cardiac dysfunction in sepsis. This study examined whether resveratrol could 
      protect against LPS-induced cardiac dysfunction by improving the sarcoplasmic 
      endoplasmic reticulum Ca(2+)-ATPase (SERCA2a) activity. Echocardiographic 
      parameters, cardiomyocyte contractile and Ca(2+) transient properties, markers 
      for cardiac inflammation, cell death, and oxidative stress, SERCA2a activity, and 
      the ratios of phospholamban (PLB) monomer to oligomer were measured. Cardiac 
      function was decreased >50% after LPS challenge (6 mg/kg for 6 h), which was 
      improved by resveratrol. There was neither difference in plasma tumor necrosis 
      factor-alpha and troponin I levels nor in infiltration of CD45(+) cells in cardiac 
      tissue between resveratrol-treated and untreated groups. In cardiomyocytes, LPS 
      significantly decreased contractile amplitude, elongated relengthening time, 
      diminished Ca(2+) transient, reduced SERCA2a activity, and increased superoxide 
      generation. These pathological alterations were attenuated by resveratrol 
      treatment. Immunoblot analysis showed that LPS-treated mice had increased levels 
      of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and the monomer form of PLB, 
      along with decreases in the levels of SERCA2a, the oligomer form of PLB and 
      nuclear factor erythroid 2-related factor (Nrf-2). Resveratrol treatment 
      upregulated SERCA2a, the oligomer form of PLB, and Nrf-2 expression and function, 
      and downregulated MDA, 4-HNE, and the monomer form of PLB. Our data suggest that 
      the activity of SERCA2a in endotoxemia is inhibited, possibly due to increases in 
      the monomer form of PLB. Resveratrol protects the heart from LPS-induced injuries 
      at least in part through promoting the oligomerization of PLB that leads to 
      enhanced SERCA2a activity.
CI  - Copyright (c) 2016 the American Physiological Society.
FAU - Bai, Tao
AU  - Bai T
AD  - Cardiovascular Center, First Hospital of Jilin University, Changchun, China; 
      Departments of Pediatrics and Radiation Oncology, Kosair Children's Hospital 
      Research Institute, University of Louisville, Louisville, Kentucky.
FAU - Hu, Xinyue
AU  - Hu X
AD  - Cardiovascular Center, First Hospital of Jilin University, Changchun, China; 
      Departments of Pediatrics and Radiation Oncology, Kosair Children's Hospital 
      Research Institute, University of Louisville, Louisville, Kentucky.
FAU - Zheng, Yang
AU  - Zheng Y
AD  - Cardiovascular Center, First Hospital of Jilin University, Changchun, China.
FAU - Wang, Shudong
AU  - Wang S
AD  - Cardiovascular Center, First Hospital of Jilin University, Changchun, China; 
      Departments of Pediatrics and Radiation Oncology, Kosair Children's Hospital 
      Research Institute, University of Louisville, Louisville, Kentucky.
FAU - Kong, Jian
AU  - Kong J
AD  - Department of Geriatric Medicine, First Hospital of Jilin University, Changchun, 
      China; and kongjian_2015@163.com.
FAU - Cai, Lu
AU  - Cai L
AD  - Departments of Pediatrics and Radiation Oncology, Kosair Children's Hospital 
      Research Institute, University of Louisville, Louisville, Kentucky.
LA  - eng
PT  - Journal Article
DEP - 20160902
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Aldehydes)
RN  - 0 (Antioxidants)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - 0 (Polymers)
RN  - 0 (Stilbenes)
RN  - 0 (Troponin I)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (phospholamban)
RN  - 11062-77-4 (Superoxides)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
RN  - K1CVM13F96 (4-hydroxy-2-nonenal)
RN  - Q369O8926L (Resveratrol)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Aldehydes/metabolism
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Blotting, Western
MH  - Calcium/metabolism
MH  - Calcium-Binding Proteins/*drug effects/metabolism
MH  - Down-Regulation
MH  - Heart/*drug effects
MH  - Immunoblotting
MH  - Lipopolysaccharides/*pharmacology
MH  - Male
MH  - Malondialdehyde/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocardial Contraction/*drug effects
MH  - Myocardium/metabolism
MH  - Myocytes, Cardiac/*drug effects/metabolism
MH  - NF-E2-Related Factor 2/drug effects/metabolism
MH  - Oxidative Stress/drug effects
MH  - Polymers/metabolism
MH  - Resveratrol
MH  - Sarcoplasmic Reticulum Calcium-Transporting ATPases/*drug effects/metabolism
MH  - Stilbenes/*pharmacology
MH  - Superoxides/metabolism
MH  - Troponin I/drug effects/metabolism
MH  - Tumor Necrosis Factor-alpha/drug effects/metabolism
MH  - Up-Regulation
OTO - NOTNLM
OT  - heart failure
OT  - nuclear factor (erythroid-derived 2)-like 2
OT  - sarcoplasmic endoplasmic reticulum calcium ion-ATPase
EDAT- 2016/09/04 06:00
MHDA- 2017/06/27 06:00
CRDT- 2016/09/04 06:00
PHST- 2016/04/13 00:00 [received]
PHST- 2016/08/06 00:00 [accepted]
PHST- 2016/09/04 06:00 [pubmed]
PHST- 2017/06/27 06:00 [medline]
PHST- 2016/09/04 06:00 [entrez]
AID - ajpheart.00296.2016 [pii]
AID - 10.1152/ajpheart.00296.2016 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2016 Oct 1;311(4):H1051-H1062. doi: 
      10.1152/ajpheart.00296.2016. Epub 2016 Sep 2.