Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ambiguous roles of genotoxic anticancer therapeutic-induced NF-kappaB activation in regulating gene expression (activation or suppression) and apoptosis (anti- or pro-apoptosis) have recently been suggested. In order to clarify this controversy and determine the usefulness of NF-kappaB blockage for sensitizing anticancer therapy, we have systematically investigated the effect of distinct NF-kappaB-blocking approaches on lung cancer cells' responses to Adriamycin-induced cytotoxicity. The results show that Adriamycin-induced NF-kappaB activation functions as a transcriptional activator triggering the expression of anti-apoptotic genes. Blocking NF-kappaB with IKKbeta- or RelA siRNA substantially sensitized Adriamycin-induced cytotoxicity, suggesting that the NF-kappaB pathway could be a target for sensitizing lung cancer cells to Adriamycin's anticancer effect. Surprisingly, although it effectively blocks NF-kappaB activation, the IkappaBalpha super-suppressor (IkappaBalphaAA) antagonized Adriamycin-induced cell death. Additionally, the induction of death receptor 5 (DR5), which contributes to Adriamycin-induced cytotoxicity, was not affected by NF-kappaB blockage. Thus, our results suggest that Adriamycin-induced NF-kappaB is a transcriptional activator that protects lung cancer cells against apoptosis, and IKKbeta- or RelA siRNA rather than IkappaBalphaAA is an appropriate NF-kappaB blocking approach for sensitizing lung cancer cells to Adriamycin-induced cytotoxicity.
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PMID:Blockage of NF-kappaB by IKKbeta- or RelA-siRNA rather than the NF-kappaB super-suppressor IkappaBalpha mutant potentiates adriamycin-induced cytotoxicity in lung cancer cells. 1863 37

BACKGROUND Previous studies of human and animal models indicate that inflammation alters lipid metabolism. The pro-protein convertase subtilisin kexin type 9 (PCSK9) plays an important role in lipid metabolism. MATERIAL AND METHODS We examined the effect of inflammation on PCSK9 expression and lipid deposition in the kidneys of mice with Adriamycin-induced nephropathy. RESULTS The results indicated an increased expression of inflammatory cytokines and lipid deposition over 12 weeks. During this time, the expression of PCSK9 and its transcriptional activator (hepatocyte nuclear factor 1alpha, HNF1alpha) decreased, and the expression of the low-density lipoprotein receptor (LDLR) and its transcriptional activator (sterol regulatory element binding protein-2, SREBP-2) increased. Exogenous inflammation appeared to further aggravate this process. CONCLUSIONS Our mouse model of nephropathy suggests that a key step in the inflammation-induced deposition of lipids in the kidneys is the downregulation renal PCSK9 expression.
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PMID:Inflammation Induces Lipid Deposition in Kidneys by Downregulating Renal PCSK9 in Mice with Adriamycin-Induced Nephropathy. 3131 82