Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclopentenone prostaglandins (PG) such as delta 12-PGJ2 and PGA are potent inhibitors of growth in a variety of cultured cells, including human epidermal cells. To clarify the mechanism of PG cytotoxicity in human epidermal cells, we examined the effects of delta 12-PGJ2 on the induction of a heat shock protein (HSP), and on the organization of cytoskeletons in the HSC-I-transformed human epidermal cell line. Immunoblot analysis using a monoclonal antibody specific for the 72-kD heat shock protein (HSP72) revealed that a 12-h incubation with 5 micrograms/ml of delta 12-PGJ2 induced HSP72 formation in HSC-I cells. HSP72 was also induced by heat shock treatment at 43 degrees C for 90 min. The quantity of HSP72 produced was markedly decreased by co-treatment with 1 microgram/ml of cycloheximide in delta 12-PGJ2-treated cells, and similarly reduced in HSC-I cells following heat treatment. Immunofluorescence using a monoclonal antibody to HSP72 demonstrated that HSP72 was localized mainly in the cytoplasm of HSC-I cells. Following treatment with 5 micrograms/ml of delta 12-PGJ2, however, HSP72 was found in the nucleolus as well as in the cytoplasm. The accumulation of HSP in the nucleolus was similarly prominent in HSC-I cells after treatment at 43 degrees C for 90 min. Addition of delta 12-PGJ2 to confluent HSC-1 cells resulted in the disappearance of actin filaments and the disarrangement of keratin filaments, as visualized with fluorescent-labeled phallacidine or immunofluorescence. These results suggest that the cytotoxicity of cyclopentenone PG is related to the induction of HSP72, and to cytoskeleton damage in transformed human epidermal cells in culture.
 ...
PMID:Induction of 72-kD heat shock protein and cytoskeleton damage by cytotoxic prostaglandin delta 12-PGJ2 in transformed human epidermal cells in culture. 137 19

Prostaglandins of the A-type (PGAs) induce heat shock protein (HSP) synthesis in a wide variety of mammalian cells resulting in protection against cellular stresses. The effect of PGAs on HSP-induction in cardiac myocytes is unknown. Therefore, we investigated the effect of PGA1 on HSP synthesis in adult rat cardiac myocytes. After 24 h of treatment, HSP72 was significantly increased 2.9-, 5.6- and 5.0-fold by PGA1 used at concentrations of 10, 20 or 40 microg/ml, respectively (P<0.05). However, the PGA1-concentration of 40 microg/ml, was found to be cytotoxic as evidenced by the release of LDH. In addition to HSP72, HSP32 was significantly increased by PGA1. The HSP32 induction was more vigorous with a marked increase with only 4 microg/ml of PGA1. No differences in the levels of HSP27, HSP60 or HSP90 were detected. When isolated cardiac myocytes were treated with PGA1, clear activation of heat shock factor (HSF) 1, one of the transcription factors for HSPs, was observed. In addition, another stress-induced transcription factor NFkappaB was also activated by PGA exposure. Despite the significant upregulation of both HSP72 and HSP32 cytoprotective properties against hypoxia and reoxygenation were absent. In conclusion, these experiments show for the first time that PGA1 induces differential expression of heat shock proteins in cardiac myocytes probably mediated through the activation of both HSF1 and NFkappaB.
 ...
PMID:Regulation of prostaglandin A1-induced heat shock protein expression in isolated cardiomyocytes. 1144 33