PMID- 7615567
OWN - NLM
STAT- MEDLINE
DCOM- 19950822
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 270
IP  - 29
DP  - 1995 Jul 21
TI  - Calcium ionophores decrease pericellular gelatinolytic activity via inhibition of 
      92-kDa gelatinase expression and decrease of 72-kDa gelatinase activation.
PG  - 17602-9
AB  - To understand the roles of intracellular calcium levels on gelatinase/type IV 
      collagenase expression, we analyzed the effects of calcium ionophores on the 
      expression of 92- and 72-kDa gelatinases (MMP-9 and MMP-2) in human fibrosarcoma 
      cells (HT-1080). Calcium ionophores ionomycin and A23187 reduced the levels of 
      pericellular gelatinolytic activity in both untreated and phorbol 12-myristate 
      13-acetate (PMA) or tumor necrosis factor-alpha (TNF alpha)-stimulated cells as 
      determined by degradation of radiolabeled gelatin. Gelatin zymography and 
      immunoblotting revealed a dose-dependent decrease in the levels of secreted 
      92-kDa gelatinase, which was paralleled by a decrease of its mRNA. Treatment of 
      cells with thapsigargin caused similar decreases of 92-kDa gelatinase mRNA and 
      protein. The decrease of 92-kDa gelatinase expression was due to lower 
      transcription rate as determined by transfection assays with 92-kDa 
      gelatinase/luciferase construct. The expression of 72-kDa gelatinase was only 
      slightly decreased by ionophores. Treatment of HT-1080 cells with PMA, TNF alpha, 
      or concanavalin A resulted in the conversion of 72-kDa gelatinase proenzyme to 
      its presumed 64- and 62-kDa active forms as determined by gelatin zymography and 
      immunoblotting. Simultaneous treatment with the ionophores or thapsigargin 
      resulted in inhibition of PMA-induced gelatinase activation. The expression of 
      membrane-type matrix metalloproteinase, a potential activator of 72-kDa 
      gelatinase, was not affected by ionophores. The results indicate that calcium 
      ionophores decrease gelatinolysis by repressing both the expression of 92-kDa 
      gelatinase and the activation of the 72-kDa gelatinase.
FAU - Lohi, J
AU  - Lohi J
AD  - Department of Virology, University of Helsinki, Finland.
FAU - Keski-Oja, J
AU  - Keski-Oja J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Ionophores)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11028-71-0 (Concanavalin A)
RN  - 37H9VM9WZL (Calcimycin)
RN  - 56092-81-0 (Ionomycin)
RN  - 9000-70-8 (Gelatin)
RN  - EC 3.4.24.- (Gelatinases)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcimycin/pharmacology
MH  - Calcium/*physiology
MH  - Concanavalin A/pharmacology
MH  - Gelatin/*metabolism
MH  - Gelatinases/*antagonists & inhibitors
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Humans
MH  - Ionomycin/pharmacology
MH  - Ionophores/*pharmacology
MH  - Molecular Weight
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Transcription, Genetic/drug effects
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 1995/07/21 00:00
MHDA- 1995/07/21 00:01
CRDT- 1995/07/21 00:00
PHST- 1995/07/21 00:00 [pubmed]
PHST- 1995/07/21 00:01 [medline]
PHST- 1995/07/21 00:00 [entrez]
AID - S0021-9258(18)95654-1 [pii]
AID - 10.1074/jbc.270.29.17602 [doi]
PST - ppublish
SO  - J Biol Chem. 1995 Jul 21;270(29):17602-9. doi: 10.1074/jbc.270.29.17602.