Different Regulation of Plasminogen Activator Inhibitor 2 Gene Expression by Phorbol Ester and cAMP in Human Myeloid Leukemia Cell Line PL-21

Kenji Niiya; Taketoshi Taniguchi; Masahiro Shinbo; Tai-ichi Ishikawa; Shigeki Tazawa; Yumiko Hayakawa; Nobuo Sakuragawa

doi:10.1055/s-0038-1648818

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1994; 72(01): 092-097
DOI: 10.1055/s-0038-1648818

Original Article

Schattauer GmbH Stuttgart

Different Regulation of Plasminogen Activator Inhibitor 2 Gene Expression by Phorbol Ester and cAMP in Human Myeloid Leukemia Cell Line PL-21

Authors

Kenji Niiya

¹The Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama
Taketoshi Taniguchi

²Medical Research Laboratory, Kochi Medical School, Nankoku, Kochi, Japan
Masahiro Shinbo

¹The Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama
Tai-ichi Ishikawa

¹The Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama
Shigeki Tazawa

¹The Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama
Yumiko Hayakawa

¹The Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama
Nobuo Sakuragawa

¹The Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama

Abstract

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Summary

Previous studies have shown that protein kinase C (PKC) activators and dibutyryl cyclic AMP (Bt2cAMP) synergistically increase the antigen level of plasminogen activator inhibitor type-2 (PAI-2) in a human myeloid leukemia cell line PL-21. To clarify the mechanism, PAI-2 gene expression induced by phorbol myristate acetate (PMA), a PKC activator, and Bt2cAMP was investigated by Northern blot hybridization using a PAI-2 cDNA probe cloned from a human placental library. The level of PAI-2 mRNA was markedly increased in response to PMA and reached a maximum 5-9 h after stimulation. Nuclear run-on assay revealed an increase in PAI-2 gene transcription in PMA-treated cells. The induction was inhibited by inhibiting de novo protein synthesis with cycloheximide (CHX). cAMP also increased PAI-2 mRNA level in a dose-dependent manner. The increase began within 2 hours and, contrary to the case of PMA, the mRNA levels were maintained. Moreover, cAMP-induced increase in PAI-2 mRNA was not inhibited by CHX, rather enhanced. PMA and cAMP synergistically induced PAI-2 gene expression, which was completely inhibited by CHX. The cells pretreated with PMA for 24 h did not any more respond to stimulation with PMA but responded to cAMP and PAI-2 mRNA level was increased. The apparent half-life of constitutive level PAI-2 mRNA in PL-21 cells, determined by actinomycin-D-decay experiments, was approximately 2 h. Those induced by PMA and cAMP were approximately 5 h and 2 h, respectively. These data suggest that PAI-2 mRNA induced by PMA is relatively stable and the expression requires de novo protein synthesis, whereas cAMP increases PAI-2 mRNA level without affecting the stability and the induction does not require de novo protein synthesis. Judging from these data, PAI-2 gene expression appears to be differently regulated by the PKC and cAMP signalling pathways.

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References

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