当前位置： SCI文献检索 > JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY期刊下所有文献 > Down-regulation of particulate protein kinase Cepsilon and up-regulation of nuclear activator protein-1 DNA binding in liver following in vivo exposure of B6C3F1 male mice to heptachlor epoxide.

Down-regulation of particulate protein kinase Cepsilon and up-regulation of nuclear activator protein-1 DNA binding in liver following in vivo exposure of B6C3F1 male mice to heptachlor epoxide.

Abstract：

:The effects of in vivo administration of the cyclodiene tumor promoter heptachlor epoxide on mouse liver protein kinase C were studied in male B6C3F1 mice by protein kinase C activity assays and Western blotting under conditions known to increase the incidence of hepatocellular carcinoma because protein kinase C is thought to be critical in phorbol ester-induced tumor promotion. Under these test conditions, 20 ppm dietary heptachlor epoxide for 1-20 days increased cytosolic and decreased particulate total protein kinase C activities, while 10 ppm had no effect. Further, total cytosolic and particulate protein kinase C activities were decreased within 1 hour by 10 mg/kg intraperitoneal (i.p.) heptachlor epoxide. Western blotting showed that conventional protein kinase Calpha and beta isoforms were unaffected by heptachlor epoxide. Particulate novel protein kinase Cepsilon, however, was selectively down-regulated by 1, 10, and 20 ppm dietary heptachlor epoxide, whereas the cytosolic isoform was decreased by 1 and 10 ppm heptachlor epoxide for 10 days. The high-dose treatment for 24 hours also decreased particulate novel protein kinase Cepsilon but increased the cytosolic titer. These results demonstrate that this isoform is unique in its sensitivity to heptachlor epoxide. Activator protein-1 DNA binding, a critical factor in tumor promotion, was substantially increased at 3 and 6 hours with 3.7 mg/kg (i.p.) heptachlor epoxide and at 3 and 10 days with 20 ppm dietary heptachlor epoxide. The effects of heptachlor epoxide on protein kinase C and activator protein-1 are similar to those caused by phorbol ester treatments and correlate well to heptachlor levels found to induce tumors in mice. However, heptachlor epoxide did not initially activate protein kinase C with in vivo treatments or with in vitro treatments of a plasma membrane fraction aimed at demonstrating direct activation, as has been shown for phorbol esters. The ability of heptachlor epoxide to down-regulate particulate novel protein kinase Cepsilon correlates to dosages used in in vivo tumor promotion studies. However, this may represent a negative feedback response rather than a causative effect.

journal_name

J Biochem Mol Toxicol

journal_title

Journal of biochemical and molecular toxicology

authors

Hansen ME,Matsumura F

doi

10.1002/1099-0461(2001)15:1<1::aid-jbt1>3.0.co;2-0

subject

Has Abstract

pub_date

2001-01-01 00:00:00

pages

1-14

issue

eissn

1095-6670

issn

1099-0461

pii

10.1002/1099-0461(2001)15:1<1::AID-JBT1>3.0.CO;2-0

journal_volume

pub_type

杂志文章

在线工具

Down-regulation of particulate protein kinase Cepsilon and up-regulation of nuclear activator protein-1 DNA binding in liver following in vivo exposure of B6C3F1 male mice to heptachlor epoxide.