PMID- 31884848
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20220531
IS  - 1473-2300 (Electronic)
IS  - 0300-0605 (Print)
IS  - 0300-0605 (Linking)
VI  - 48
IP  - 4
DP  - 2020 Apr
TI  - Activation of autophagy during farnesyl pyrophosphate synthase inhibition is 
      mediated through PI3K/AKT/mTOR signaling.
PG  - 300060519875371
LID - 10.1177/0300060519875371 [doi]
LID - 0300060519875371
AB  - OBJECTIVES: Autophagy is divided into three phases: autophagosome engulfment of 
      intracellular organelles and proteins, autophagosome fusion with lysosomes, and 
      autolysosome degradation. The farnesyl pyrophosphate synthase inhibitor 
      ibandronate (IBAN) has in vivo cardioprotective properties, potentially via 
      anti-oxidant effects. Whether autophagy is involved in the cardioprotective 
      effect of IBAN remains unexplored. METHODS: Human umbilical vein endothelial 
      cells (HUVECs) were treated in vitro with IBAN to assess autophagy induction. 
      Lysosomal activation and phosphatidylinositol 3-kinase (PI3K)/protein kinase B 
      (AKT)/mammalian target of rapamycin (mTOR) signaling were assessed using a 
      LysoTracker assay, acridine orange staining and western blotting. An MTS assay 
      was used to assess cellular proliferation. Autophagy was inhibited using 
      chloroquine or RNA silencing of autophagy-related 7 (Atg7) expression. RESULTS: 
      IBAN induced autophagy in HUVECs. Moreover, IBAN activated lysosomal function, 
      which is pivotal to autophagy induction. PI3K/AKT/mTOR activity was inhibited in 
      IBAN-treated HUVECs, indicating the involvement of this pathway in IBAN-induced 
      autophagy. Inhibition of autophagy using either chloroquine or Atg7 siRNA 
      potentiated inhibition of HUVEC growth by IBAN, suggesting the involvement of 
      non-autophagy pathways in the antiproliferative effects of IBAN. CONCLUSIONS: 
      These findings provide insights into the role of autophagy in the 
      cardioprotective effects of IBAN and the molecular mechanisms underlying 
      autophagy induction by IBAN.
FAU - Han, Jie
AU  - Han J
AD  - Department of Cardiology, The First Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, Zhejiang, China.
FAU - Huang, Chaoyang
AU  - Huang C
AD  - Department of Cardiology, The First Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, Zhejiang, China.
FAU - Jiang, Jiukun
AU  - Jiang J
AD  - Department of Emergency, The First Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, Zhejiang, China.
FAU - Jiang, Dongmei
AU  - Jiang D
AUID- ORCID: 0000-0002-7926-8645
AD  - Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang 
      University, Hangzhou, Zhejiang, China.
LA  - eng
PT  - Journal Article
DEP - 20191229
PL  - England
TA  - J Int Med Res
JT  - The Journal of international medical research
JID - 0346411
RN  - 0 (Polyisoprenyl Phosphates)
RN  - 0 (Sesquiterpenes)
RN  - EC 2.5.1.10 (Geranyltranstransferase)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Apoptosis
MH  - *Autophagy
MH  - Geranyltranstransferase/*antagonists & inhibitors
MH  - Humans
MH  - Phosphatidylinositol 3-Kinases/genetics
MH  - Polyisoprenyl Phosphates
MH  - Proto-Oncogene Proteins c-akt/genetics
MH  - Sesquiterpenes
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/genetics
PMC - PMC7607048
OTO - NOTNLM
OT  - Atg7
OT  - Autophagy
OT  - FPPS
OT  - HUVECs
OT  - IBAN
OT  - mTOR
COIS- The authors declare that there are no conflicts of interest.
EDAT- 2019/12/31 06:00
MHDA- 2021/05/15 06:00
PMCR- 2019/12/29
CRDT- 2019/12/31 06:00
PHST- 2019/12/31 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2019/12/31 06:00 [entrez]
PHST- 2019/12/29 00:00 [pmc-release]
AID - 10.1177_0300060519875371 [pii]
AID - 10.1177/0300060519875371 [doi]
PST - ppublish
SO  - J Int Med Res. 2020 Apr;48(4):300060519875371. doi: 10.1177/0300060519875371. 
      Epub 2019 Dec 29.