PMID- 21738216
OWN - NLM
STAT- MEDLINE
DCOM- 20120501
LR  - 20220310
IS  - 1476-5403 (Electronic)
IS  - 1350-9047 (Print)
IS  - 1350-9047 (Linking)
VI  - 19
IP  - 2
DP  - 2012 Feb
TI  - TNF-alpha response of vascular endothelial and vascular smooth muscle cells involve 
      differential utilization of ASK1 kinase and p73.
PG  - 274-83
LID - 10.1038/cdd.2011.93 [doi]
AB  - Atherosclerosis involves a specialized inflammatory process regulated by an 
      intricate network of cytokine and chemokine signaling. Atherosclerotic lesions 
      lead to the release of cytokines that can have multiple affects on various 
      vascular cell functions either promoting lesion expansion or alternatively retard 
      progression. Tumor necrosis factor-alpha (TNF-alpha) is one such cytokine that can 
      activate both cell survival and cell death mechanisms simultaneously. Here we 
      show that TNF-alpha induces apoptosis in human aortic endothelial cells (HAECs), 
      while it promotes the proliferation of vascular smooth muscle cells (VSMCs). Both 
      events involved the activation of the Rb-E2F1 transcriptional regulatory pathway. 
      Stimulation of HAECs with TNF-alpha led to an increased expression of p73 protein and 
      a reduction in the levels of p53. This involved apoptosis signal-regulating 
      kinase 1 (ASK1)- mediated inactivation of Rb and its dissociation from the p73 
      promoter. In contrast, TNF-alpha stimulation of VSMCs enhanced the association of 
      E2F1 with proliferative promoters like thymidylate synthase and cdc25A, while Rb 
      was dissociated. ASK1 kinase has a critical role in the apoptotic process, as its 
      depletion or dissociation from Rb reduced TNF-alpha-induced apoptosis. These results 
      show that the cytokine TNF-alpha can elicit diametrically opposite responses in 
      vascular endothelial cells and VSMCs, utilizing the Rb-E2F pathway.
FAU - Rastogi, S
AU  - Rastogi S
AD  - Department of Tumor Biology, H Lee Moffitt Cancer Center and Research Institute, 
      12902 Magnolia Drive, Tampa, FL 33612, USA.
FAU - Rizwani, W
AU  - Rizwani W
FAU - Joshi, B
AU  - Joshi B
FAU - Kunigal, S
AU  - Kunigal S
FAU - Chellappan, S P
AU  - Chellappan SP
LA  - eng
GR  - R01 CA063136/CA/NCI NIH HHS/United States
GR  - R01 CA063136-15/CA/NCI NIH HHS/United States
GR  - CA63136/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110708
PL  - England
TA  - Cell Death Differ
JT  - Cell death and differentiation
JID - 9437445
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (E2F1 Transcription Factor)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (TP73 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Tumor Protein p73)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 5)
SB  - IM
MH  - Aorta/cytology
MH  - Apoptosis/drug effects/genetics
MH  - Cell Proliferation/drug effects
MH  - Cytoprotection/drug effects
MH  - DNA-Binding Proteins/*metabolism
MH  - E2F1 Transcription Factor/metabolism
MH  - Endothelial Cells/cytology/drug effects/*enzymology
MH  - Endothelium, Vascular/*cytology
MH  - Gene Silencing/drug effects
MH  - Humans
MH  - MAP Kinase Kinase Kinase 5/*metabolism
MH  - Muscle, Smooth, Vascular/*cytology
MH  - Myocytes, Smooth Muscle/cytology/drug effects/*enzymology
MH  - Nuclear Proteins/*metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding/drug effects
MH  - RNA, Small Interfering/metabolism
MH  - Retinoblastoma Protein/metabolism
MH  - Transcription, Genetic/drug effects
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Tumor Protein p73
MH  - Tumor Suppressor Protein p53/metabolism
MH  - Tumor Suppressor Proteins/*metabolism
PMC - PMC3191254
MID - NIHMS298069
EDAT- 2011/07/09 06:00
MHDA- 2012/05/02 06:00
PMCR- 2013/02/01
CRDT- 2011/07/09 06:00
PHST- 2011/07/09 06:00 [entrez]
PHST- 2011/07/09 06:00 [pubmed]
PHST- 2012/05/02 06:00 [medline]
PHST- 2013/02/01 00:00 [pmc-release]
AID - cdd201193 [pii]
AID - 10.1038/cdd.2011.93 [doi]
PST - ppublish
SO  - Cell Death Differ. 2012 Feb;19(2):274-83. doi: 10.1038/cdd.2011.93. Epub 2011 Jul 
      8.