PMID- 32539921
OWN - NLM
STAT- MEDLINE
DCOM- 20210520
LR  - 20210520
IS  - 0031-7144 (Print)
IS  - 0031-7144 (Linking)
VI  - 75
IP  - 6
DP  - 2020 Jun 1
TI  - Inhibition of JAK2 by AG490 promotes TNF-alpha-induced apoptosis by inhibiting 
      autophagy in MC3T3-E1 cells.
PG  - 255-260
LID - 10.1691/ph.2020.0375 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha), one of the pro-inflammatory factors in 
      osteoporosis, has a strong enhancement effect on osteoclastogenesis and 
      disruption of osteoblast survival and function. JAK2 participates in a wide range 
      of biological processes, including bone homeostasis, but its function in 
      osteoblast survival in inflammatory environments remains unknown. In this study, 
      flow cytometry and immunofluorescence staining of LC3B were performed under TNF-alpha 
      stimulation in MC3T3-E1 cells. Apoptosis-related protein Cleaved PARP and 
      autophagy-related protein LC3 were upregulated, meanwhile, p62 was downregulated 
      by TNF-alpha. JAK2 signaling was also activated in the process. AG490 was used to 
      inhibit JAK2 signaling, which promoted apoptosis and attenuated autophagy induced 
      by TNF-alpha. Enhancement of autophagy by rapamycin reversed the promotional effect 
      of AG490 on apoptosis, and the autophagy inhibitor chloroquine further enhanced 
      apoptosis. Western blot analysis showed that the STAT3, Akt, and Erk signaling 
      pathways are involved in AG490 treatment. This study demonstrated for the first 
      time that JAK2 inhibition by AG490 may play a crucial role in TNF-alpha-induced 
      apoptosis by inhibiting autophagy and inhibiting the STAT3, Akt, and Erk 
      signaling pathways.
FAU - Ni, Yifeng
AU  - Ni Y
AD  - The State Key Laboratory Breeding Base of Basic Science of Stomatology 
      (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & 
      Hospital of Stomatology, Wuhan University, Wuhan, China.
FAU - Zhang, Hao
AU  - Zhang H
AD  - The State Key Laboratory Breeding Base of Basic Science of Stomatology 
      (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & 
      Hospital of Stomatology, Wuhan University, Wuhan, China.
FAU - Zhang, Jing
AU  - Zhang J
AD  - The State Key Laboratory Breeding Base of Basic Science of Stomatology 
      (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & 
      Hospital of Stomatology, Wuhan University, Wuhan, China.
FAU - Li, Zhi
AU  - Li Z
AD  - The State Key Laboratory Breeding Base of Basic Science of Stomatology 
      (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & 
      Hospital of Stomatology, Wuhan University, Wuhan, China;, Email: 
      lizhi@whu.edu.cn.
FAU - Li, Zubing
AU  - Li Z
AD  - The State Key Laboratory Breeding Base of Basic Science of Stomatology 
      (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & 
      Hospital of Stomatology, Wuhan University, Wuhan, China;, Email: 
      lizubing@whu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Pharmazie
JT  - Die Pharmazie
JID - 9800766
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Tyrphostins)
RN  - 0 (alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide)
RN  - 886U3H6UFF (Chloroquine)
RN  - EC 2.7.10.2 (Jak2 protein, mouse)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Autophagy/*drug effects
MH  - Chloroquine/pharmacology
MH  - Flow Cytometry
MH  - Janus Kinase 2/*antagonists & inhibitors
MH  - MAP Kinase Signaling System/drug effects
MH  - Mice
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirolimus/pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Tyrphostins/*pharmacology
EDAT- 2020/06/17 06:00
MHDA- 2021/05/21 06:00
CRDT- 2020/06/17 06:00
PHST- 2020/06/17 06:00 [entrez]
PHST- 2020/06/17 06:00 [pubmed]
PHST- 2021/05/21 06:00 [medline]
AID - 10.1691/ph.2020.0375 [doi]
PST - ppublish
SO  - Pharmazie. 2020 Jun 1;75(6):255-260. doi: 10.1691/ph.2020.0375.