PMID- 10926555
OWN - NLM
STAT- MEDLINE
DCOM- 20000831
LR  - 20200930
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 279
IP  - 2
DP  - 2000 Aug
TI  - TNF-alpha increases transcription of Galpha(i-2) in human airway smooth muscle 
      cells.
PG  - L319-25
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that has an 
      important role in the regulation of airway smooth muscle tone and reactivity. We 
      have shown previously that TNF-alpha upregulates the expression of Galpha(i-2) 
      protein without significantly increasing G(s)alpha protein and enhances adenylyl 
      cyclase inhibition by carbachol in cultured human airway smooth muscle cells 
      (Hotta K, Emala CW, and Hirshman CA. Am J Physiol Lung Cell Mol Physiol 276: 
      L405-L411, 1999). The present study was designed to investigate the molecular 
      mechanisms by which TNF-alpha upregulates Galpha(i-2) protein in these cells. 
      TNF-alpha pretreatment for 48 h increased the expression of Galpha(i-2) protein 
      without significantly altering the Galpha(i-2) protein half-life (41.0 +/- 8.2 h 
      for control and 46.8 +/- 5.2 h for TNF-alpha-treated cells). Inhibition of new 
      protein synthesis by cycloheximide blocked the increase in Galpha(i-2) protein 
      induced by TNF-alpha. Furthermore, TNF-alpha treatment for 12-24 h increased the 
      steady-state level of Galpha(i-2) mRNA without significantly altering Galpha(i-2) 
      mRNA half-life (9.0 +/- 0.75 h for control and 8.9 +/- 1.1 h for 
      TNF-alpha-treated cells). The transcription inhibitor actinomycin D blocked the 
      increase in Galpha(i-2) mRNA induced by TNF-alpha. These observations indicate 
      that the increase in Galpha(i-2) protein induced by TNF-alpha is due to an 
      increased rate of Galpha(i-2) protein synthesis, most likely as a consequence of 
      the transcriptional increase in the steady-state levels of its mRNA.
FAU - Hotta, K
AU  - Hotta K
AD  - Department of Anesthesiology, College of Physicians and Surgeons of Columbia 
      University, New York, New York 10032, USA.
FAU - Hirshman, C A
AU  - Hirshman CA
FAU - Emala, C W
AU  - Emala CW
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Nucleic Acid Synthesis Inhibitors)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1CC1JFE158 (Dactinomycin)
RN  - 98600C0908 (Cycloheximide)
RN  - EC 3.6.5.1 (GNAI2 protein, human)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunit, Gi2)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gi-Go)
RN  - EC 3.6.5.1 (Heterotrimeric GTP-Binding Proteins)
SB  - IM
MH  - Cell Count/drug effects
MH  - Cells, Cultured
MH  - Cycloheximide/pharmacology
MH  - Dactinomycin/pharmacology
MH  - GTP-Binding Protein alpha Subunit, Gi2
MH  - *GTP-Binding Protein alpha Subunits, Gi-Go
MH  - Gene Expression Regulation/drug effects
MH  - Heterotrimeric GTP-Binding Proteins/*biosynthesis/genetics
MH  - Humans
MH  - Immunoblotting
MH  - Muscle, Smooth/cytology/*metabolism
MH  - Nucleic Acid Synthesis Inhibitors/pharmacology
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - Proto-Oncogene Proteins/*biosynthesis/genetics
MH  - RNA, Messenger/metabolism
MH  - Trachea/cytology/*metabolism
MH  - Transcription, Genetic/*drug effects
MH  - Tumor Necrosis Factor-alpha/*metabolism/pharmacology
EDAT- 2000/08/05 11:00
MHDA- 2000/09/02 11:01
CRDT- 2000/08/05 11:00
PHST- 2000/08/05 11:00 [pubmed]
PHST- 2000/09/02 11:01 [medline]
PHST- 2000/08/05 11:00 [entrez]
AID - 10.1152/ajplung.2000.279.2.L319 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2000 Aug;279(2):L319-25. doi: 
      10.1152/ajplung.2000.279.2.L319.