Interference with mitogenic signal transduction by polychlorinated dibenzo-p-dioxin in vascular smooth muscle cells : a focus on protein phosphorylation, c-Ha-ras, and cell proliferation /
Studies were conducted to test the hypothesis that the
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
1994.
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| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=741966031&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | Studies were conducted to test the hypothesis that the effects of BaP on PKC activity in rat aortic SMCs were partly mediated through an aryl hydrocarbon receptor (AhR)-related mechanism and assess the cell cycle-dependence of these responses. Enhanced PKC activity was observed in rat aortic SMCs isolated from rats treated with TCDD in vivo as well as in naive cultured randomly cycling SMCs in vitro. Sucrose density gradient and gel mobility shift analysis of SMCs treated with TCDD suggested this cell type contains an intact AhR signal transduction system. Structure-activity relationships conducted in growth-arrested SMCs treated with TCDD suggested both AhR-related and -independent components. PKC activity was differentially effected by TCDD during individual phases of the cell cycle where reduced C-kinase activity during the GO/GI transition and increased activity during the Gi/S transition were observed. Enhanced PKC activity during the GI/S transition was cycloheximide insensitive suggesting that modulation of PKC activity during this phase of the cell cycle was not related to de novo protein synthesis. Western blot analysis showed the presence of 5 PKC subspecies in cultured rat aortic SMCS, namely the PKC (X, PKC 011, PKC8, PKCF-, and PKCC, isoforms. Treatment of synchronized cycling SMCs with TCDD during the GO/GI transition decreased expression of all PKC isoforms. PKCPH and PKC8 were increased in SMCs treated with TCDD during the Gi/S transition, PKCC expression was slightly reduced, and PKC(X and F were unaffected. Reduced DNA synthetic rates were observed in SMCs treated with TCDD during the early GO/G 1 phase. Flow cytometry confirmed reductions of DNA synthesis and suggested that TCDD impeded cell cycle progression. Modulation of PKC activity and DNA synthesis during the early Go/G i phase were associated with reductions of inducible AP- I:TRE binding activity in nuclear extracts from quiescent SMCs treated with serum and TCDD. Measurement of DNA synthetic rates in naive and c-Ha-rasEJ transfected SMCs in the presence of staurosporine and in PKC-depleted cells suggested that PKC was a critical component of growth- related signal transduction in vascular SMCS. |
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| Item Description: | Vita. "Major Subject: Toxicology". In title, symbols are used. |
| Physical Description: | xii, 167 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilms Inc. |
| Bibliography: | Includes bibliographical references. |