PMID- 23705975
OWN - NLM
STAT- MEDLINE
DCOM- 20130904
LR  - 20220410
IS  - 1557-7430 (Electronic)
IS  - 1044-5498 (Linking)
VI  - 32
IP  - 7
DP  - 2013 Jul
TI  - Both PI3K- and mTOR-signaling pathways take part in CVB3-induced apoptosis of 
      Hela cells.
PG  - 359-70
LID - 10.1089/dna.2013.2003 [doi]
AB  - This work illustrated the mechanism contributing to the process of 
      Phosphatidylinostiol 3-kinase (PI3K)/protein kinase B (PKB)/mammalian target of 
      rapamycin (mTOR) signaling pathway, which has been demonstrated to play an 
      important role in virus-induced apoptosis, which contributes to the Viral 
      Myocarditis (VMC) pathogeneses. We examined the expression of Bax, Bim, 
      caspase-3, caspase-9, and viral replication after Coxsackievirus B3 (CVB3) 
      infection using the mTOR inhibitor and PI3K inhibitor pretreated HeLa cells, 
      respectively. Apoptosis in different groups was determined by flow cytometry. 
      Bax, Bim, caspase-9, and caspase-3 were examined by semiquantitative polymerase 
      chain reaction (PCR) and Western blot analysis. The expression of CVB3 mRNA and 
      viral capsid protein VP1 were analyzed by semiquantitative PCR and Western blot 
      analysis distinctively. We found that rapamycin and LY294002 promote CVB3-induced 
      cytopathic effect (CPE) and apoptosis. CVB3 replication in host cells is mediated 
      in mRNA and protein expression by rapamycin and LY294002. Moreover, comparing 
      with controls, at 12 and 24 h of postinfection (p.i.), Bim and Bax expression 
      increased in cells after treated with rapamycin or LY294002, which also 
      stimulates the activation of procaspase-9, and the CVB3-induced caspase-3 
      self-cleavage. However, in the meantime, the mRNA expression of caspase-9 and 
      caspase-3 did not have an obvious change. In summary, our results demonstrated 
      that the mTOR-signaling pathway plays an important role in CVB3-induced CPE and 
      apoptosis, which is indispensable in VMC, via regulating Bim, Bax, caspase-9, 
      caspase-3, and viral replication. Our findings may provide a new perspective and 
      a deeper understanding of the mechanism of CVB3-induced apoptosis which, in turn, 
      may help with the development of new therapy for the CVB3 infection.
FAU - Li, Xin
AU  - Li X
AD  - Department of Pediatrics, The Third Xiangya Hospital, Central South University, 
      Changsha, China.
FAU - Zhang, Juan
AU  - Zhang J
FAU - Chen, Zhiheng
AU  - Chen Z
FAU - Yang, Li
AU  - Yang L
FAU - Xing, Xiaowei
AU  - Xing X
FAU - Ma, Xing
AU  - Ma X
FAU - Yang, Zuocheng
AU  - Yang Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130525
PL  - United States
TA  - DNA Cell Biol
JT  - DNA and cell biology
JID - 9004522
RN  - 0 (Chromones)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Morpholines)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - *Apoptosis/drug effects
MH  - Cells, Cultured
MH  - Chromones/pharmacology
MH  - Coxsackievirus Infections/*metabolism
MH  - Enterovirus B, Human/*isolation & purification
MH  - Enzyme Inhibitors/pharmacology
MH  - HeLa Cells/virology
MH  - Humans
MH  - Morpholines/pharmacology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - *Signal Transduction/drug effects/physiology
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/*metabolism
EDAT- 2013/05/28 06:00
MHDA- 2013/09/05 06:00
CRDT- 2013/05/28 06:00
PHST- 2013/05/28 06:00 [entrez]
PHST- 2013/05/28 06:00 [pubmed]
PHST- 2013/09/05 06:00 [medline]
AID - 10.1089/dna.2013.2003 [doi]
PST - ppublish
SO  - DNA Cell Biol. 2013 Jul;32(7):359-70. doi: 10.1089/dna.2013.2003. Epub 2013 May 
      25.