PMID- 31929843
OWN - NLM
STAT- MEDLINE
DCOM- 20200511
LR  - 20220412
IS  - 1875-8630 (Electronic)
IS  - 0278-0240 (Print)
IS  - 0278-0240 (Linking)
VI  - 2019
DP  - 2019
TI  - Thyroxine Alleviates Energy Failure, Prevents Myocardial Cell Apoptosis, and 
      Protects against Doxorubicin-Induced Cardiac Injury and Cardiac Dysfunction via 
      the LKB1/AMPK/mTOR Axis in Mice.
PG  - 7420196
LID - 10.1155/2019/7420196 [doi]
LID - 7420196
AB  - BACKGROUND: Previous studies have demonstrated that energy failure is closely 
      associated with cardiac injury. Doxorubicin (DOX) is a commonly used clinical 
      chemotherapy drug that can mediate cardiac injury through a variety of 
      mechanisms. Thyroxine is well known to play a critical role in energy generation; 
      thus, this study is aimed at investigating whether thyroxine can attenuate 
      DOX-induced cardiac injury by regulating energy generation. METHODS: First, the 
      effect of DOX on adenosine diphosphate (ADP) and adenosine triphosphate (ATP) 
      ratios in mice was assessed. In addition, thyroxine was given to mice before they 
      were treated with DOX to investigate the effects of thyroxine on DOX-induced 
      cardiac injury. Furthermore, to determine whether the liver kinase b1 
      (LKB1)/adenosine 5'-monophosphate-activated protein kinase (AMPK)/mammalian 
      target of rapamycin (mTOR) axis mediated the effect of thyroxine on DOX-induced 
      cardiac injury, thyroxine was given to DOX-treated LKB1 knockout (KO) mice. 
      RESULTS: DOX treatment time- and dose-dependently increased the ADP/ATP ratio. 
      Thyroxine treatment also reduced lactate dehydrogenase (LDH) and creatine kinase 
      myocardial band (CK-MB) levels in both serum and heart tissue and alleviated 
      cardiac dysfunction in DOX-treated mice. Furthermore, thyroxine reversed 
      DOX-induced reductions in LKB1 and AMPK phosphorylation; mitochondrial complex I, 
      III, and IV activity; and mitochondrial swelling and reversed DOX-induced 
      increases in mTOR pathway phosphorylation and myocardial cell apoptosis. These 
      effects of thyroxine on DOX-treated mice were significantly attenuated by LKB1 
      KO. CONCLUSIONS: Thyroxine alleviates energy failure, reduces myocardial cell 
      apoptosis, and protects against DOX-induced cardiac injury via the LKB1/AMPK/mTOR 
      axis in mice. Thyroxine may be a new agent for the clinical prevention of cardiac 
      injury in tumor patients undergoing chemotherapy with DOX.
CI  - Copyright (c) 2019 Yuan Wang et al.
FAU - Wang, Yuan
AU  - Wang Y
AD  - Department of Thyroid Breast Surgery, Renmin Hospital of Wuhan University, Wuhan 
      430060, China.
FAU - Zhu, Shan
AU  - Zhu S
AD  - Department of Thyroid Breast Surgery, Renmin Hospital of Wuhan University, Wuhan 
      430060, China.
FAU - Liu, Hongtao
AU  - Liu H
AD  - Department of Cardiovascular Medicine, Shenzhen Longhua District Central 
      Hospital, Longhua Central Hospital Affiliated with Guangdong Medical University, 
      Shenzhen, Guangdong Province 518110, China.
FAU - Wei, Wen
AU  - Wei W
AD  - Department of Thyroid Breast Surgery, Renmin Hospital of Wuhan University, Wuhan 
      430060, China.
FAU - Tu, Yi
AU  - Tu Y
AD  - Department of Thyroid Breast Surgery, Renmin Hospital of Wuhan University, Wuhan 
      430060, China.
FAU - Chen, Chuang
AU  - Chen C
AD  - Department of Thyroid Breast Surgery, Renmin Hospital of Wuhan University, Wuhan 
      430060, China.
FAU - Song, Junlong
AU  - Song J
AD  - Department of Thyroid Breast Surgery, Renmin Hospital of Wuhan University, Wuhan 
      430060, China.
FAU - Li, Juanjuan
AU  - Li J
AD  - Department of Thyroid Breast Surgery, Renmin Hospital of Wuhan University, Wuhan 
      430060, China.
FAU - Sun, Shengrong
AU  - Sun S
AUID- ORCID: 0000-0003-2893-6735
AD  - Department of Thyroid Breast Surgery, Renmin Hospital of Wuhan University, Wuhan 
      430060, China.
FAU - Wang, Changhua
AU  - Wang C
AUID- ORCID: 0000-0003-2817-2552
AD  - Basic Medical School of Wuhan University, Wuhan 430060, China.
FAU - Xu, Zhiliang
AU  - Xu Z
AUID- ORCID: 0000-0003-0957-2286
AD  - Department of Thyroid Breast Surgery, Renmin Hospital of Wuhan University, Wuhan 
      430060, China.
LA  - eng
PT  - Journal Article
DEP - 20191216
PL  - United States
TA  - Dis Markers
JT  - Disease markers
JID - 8604127
RN  - 61D2G4IYVH (Adenosine Diphosphate)
RN  - 80168379AG (Doxorubicin)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Stk11 protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - Q51BO43MG4 (Thyroxine)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Adenosine Diphosphate/metabolism
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Doxorubicin/*adverse effects
MH  - Heart Diseases/chemically induced/*drug therapy/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Myocytes, Cardiac/cytology/drug effects
MH  - Protein Serine-Threonine Kinases/*genetics
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Thyroxine/*administration & dosage/pharmacology
PMC - PMC6935797
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2020/01/14 06:00
MHDA- 2020/05/12 06:00
PMCR- 2019/12/16
CRDT- 2020/01/14 06:00
PHST- 2019/05/07 00:00 [received]
PHST- 2019/10/28 00:00 [revised]
PHST- 2019/11/19 00:00 [accepted]
PHST- 2020/01/14 06:00 [entrez]
PHST- 2020/01/14 06:00 [pubmed]
PHST- 2020/05/12 06:00 [medline]
PHST- 2019/12/16 00:00 [pmc-release]
AID - 10.1155/2019/7420196 [doi]
PST - epublish
SO  - Dis Markers. 2019 Dec 16;2019:7420196. doi: 10.1155/2019/7420196. eCollection 
      2019.