PMID- 25109305
OWN - NLM
STAT- MEDLINE
DCOM- 20150522
LR  - 20211203
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 10
IP  - 4
DP  - 2014 Oct
TI  - Ulinastatin protects cardiomyocytes against ischemia‑reperfusion injury by 
      regulating autophagy through mTOR activation.
PG  - 1949-53
LID - 10.3892/mmr.2014.2450 [doi]
AB  - Autophagy is significant in myocardial ischemia-reperfusion (IR) injury. 
      Ulinastatin has been demonstrated to protect cardiomyocytes against IR through 
      inducing anti-inflammatory effects. However, whether ulinastatin has an 
      anti‑autophagic effect is yet to be elucidated. The present study aimed to 
      investigate the effect of ulinastatin on the regulation of autophagy during IR 
      injury. Cardiomyocytes of neonatal rats were randomly divided into control, 
      hypoxia-reoxygenation (HR) and ulinastatin groups. In order to investigate 
      whether mammalian target of rapamycin (mTOR) is involved in mediating the 
      protective effect of ulinastatin, cells were treated with the mTOR inhibitor, 
      rapamycin 30 min prior to ulinastatin treatment. To demonstrate the 
      anti-autophagic effect of ulinastatin in vivo, a rat IR model was established. 
      Ulinastatin (1x104 U/kg body weight) was administered 30 min prior to the 
      induction of IR via peritoneal injection. Light chain 3 (LC3), phosphorylated 
      (p)‑mTOR, p‑protein kinase B (Akt) and p‑P70S6 kinase (p‑P70S6K) protein 
      expression were assessed using western blot analysis. In addition, cell vitality, 
      myocardial infarct size and lactate dehydrogenase (LDH) levels were measured. 
      LC3‑Ⅱ protein expression was found to be downregulated, while p‑Akt, p‑mTOR and 
      p‑P70S6K protein expression were observed to be upregulated by ulinastatin. In 
      addition, cell vitality was found to increase and LDH was observed to decrease in 
      the ulinastatin group compared with the HR group in vitro. Furthermore, rapamycin 
      was found to attenuate the myocardial protective effect that is induced by 
      ulinastatin. In vivo, ulinastatin was found to downregulate LC3‑Ⅱ protein 
      expression, and reduce myocardium infarct size and LDH serum levels. These 
      findings indicate that ulinastatin exhibits a myocardial protective effect 
      against IR injury by regulating autophagy through mTOR activation.
FAU - Xiao, Jian
AU  - Xiao J
AD  - Department of Cardiothoracic Surgery, Changzheng Hospital, The Second Military 
      Medical University, Shanghai 200003, P.R. China.
FAU - Zhu, Xiaoyan
AU  - Zhu X
AD  - Department of Physiology, The Second Military Medical University, Shanghai 
      200433, P.R. China.
FAU - Ji, Guangyu
AU  - Ji G
AD  - Department of Cardiothoracic Surgery, Changzheng Hospital, The Second Military 
      Medical University, Shanghai 200003, P.R. China.
FAU - Yang, Qian
AU  - Yang Q
AD  - Department of Cardiothoracic Surgery, Changzheng Hospital, The Second Military 
      Medical University, Shanghai 200003, P.R. China.
FAU - Kang, Bo
AU  - Kang B
AD  - Department of Cardiothoracic Surgery, Changzheng Hospital, The Second Military 
      Medical University, Shanghai 200003, P.R. China.
FAU - Zhao, Jianquan
AU  - Zhao J
AD  - Department of Cardiothoracic Surgery, Changzheng Hospital, The Second Military 
      Medical University, Shanghai 200003, P.R. China.
FAU - Yao, Feng
AU  - Yao F
AD  - Department of Anesthesiology, Shanghai Chest Hospital Affiliated to Shanghai 
      Jiaotong University, Shanghai 200030, P.R. China.
FAU - Wu, Lihui
AU  - Wu L
AD  - Department of Cardiothoracic Surgery, Changzheng Hospital, The Second Military 
      Medical University, Shanghai 200003, P.R. China.
FAU - Ni, Xin
AU  - Ni X
AD  - Department of Physiology, The Second Military Medical University, Shanghai 
      200433, P.R. China.
FAU - Wang, Zhinong
AU  - Wang Z
AD  - Department of Cardiothoracic Surgery, Changzheng Hospital, The Second Military 
      Medical University, Shanghai 200003, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140805
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Glycoproteins)
RN  - 0 (LC3 protein, rat)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Protective Agents)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - OR3S9IF86U (urinastatin)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Autophagy/*drug effects
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Down-Regulation/drug effects
MH  - Glycoproteins/*pharmacology
MH  - Male
MH  - Microtubule-Associated Proteins/metabolism
MH  - Myocytes, Cardiac/cytology/*drug effects
MH  - Phosphorylation/drug effects
MH  - Protective Agents/*pharmacology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reperfusion Injury/metabolism/pathology
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Sirolimus/toxicity
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
MH  - Up-Regulation/drug effects
EDAT- 2014/08/12 06:00
MHDA- 2015/05/23 06:00
CRDT- 2014/08/12 06:00
PHST- 2013/10/23 00:00 [received]
PHST- 2013/12/06 00:00 [accepted]
PHST- 2014/08/12 06:00 [entrez]
PHST- 2014/08/12 06:00 [pubmed]
PHST- 2015/05/23 06:00 [medline]
AID - 10.3892/mmr.2014.2450 [doi]
PST - ppublish
SO  - Mol Med Rep. 2014 Oct;10(4):1949-53. doi: 10.3892/mmr.2014.2450. Epub 2014 Aug 5.