Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been shown that ultrasound (US) stimulation accelerates fracture healing, bone maturation, and remodeling in the animal models and in clinical studies. One of the major factor involves in remodeling process is matrix metalloproteinases (MMPs) such as MMP-13 that has been shown to degrade the native interstitial collagens in several tissues. Here we found that US stimulation increased the secretion of MMP-13 in cultured rat osteoblasts, as shown by zymographic analysis. US stimulation also increased the mRNA level of MMP-13, c-Fos, and c-Jun. Cycloheximide (an inhibitor of protein translocation) and actinomycin D (an inhibitor of gene transcription) did not inhibit the MMP-13, c-Fos, and c-Jun mRNA expression, suggesting that such expression does not require de novo protein synthesis and not change their stabilities. p38 inhibitor, SB203580 or JNK inhibitor, SP600125 but not ERK inhibitor, PD98059 attenuated the US-induced MMP-13, c-Fos, and c-Jun expression; these results were further substantiated by transfecting with the dominant negative mutants of p38 or JNK. The binding of c-Fos and c-Jun to the AP-1 element on the MMP-13 promoter and the enhancement of AP-1 luciferase activity was enhanced by US stimulation. Taken together, our results provide evidence that US stimulation increases MMP-13 expression through p38 and JNK signaling pathway to regulate bone remodeling.
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PMID:Ultrasound stimulates MMP-13 expression through p38 and JNK pathway in osteoblasts. 1794 Oct 91

The level of proenkephalin mRNA in bovine adrenal chromaffin cells was studied in the presence of cycloheximide, an inhibitor of translation, and two modulators of proenkephalin synthesis, nicotine and 12-O-tetradecanoylphorbol-13-acetate (TPA). Cycloheximide (CHX) abolished the induction of proenkephalin mRNA expression and protein synthesis by these two modulators, indicating that de novo protein synthesis was necessary for proenkephalin gene activation. The transcriptional regulatory regions of the proenkephalin gene displayed an extremely high degree of interspecies sequence conservation between humans, rats, and cows. In addition, molecular analyses of the human proenkephalin gene defined a cluster of responsive elements, designated as ENKCRE-1, ENKCRE-2, and AP-2; ENKCRE-2 acted functionally like both an AP-1 motif and a CAMP responsive element (CRE). When oligonucleotides containing ENKCRE-1, ENKCRE-2, AP-2, AP-1, and CRE motifs were used in protein-DNA gel mobility retardation experiments, the induction of ENKCRE-2/AP-1 activity correlated well with the level of proenkephalin mRNA induction. This ENKCRE-2/AP-1 complex could be inhibited by a specific c-Jun antiserum and was super-shifted by a polyclonal antibody against the Fos family of proteins. Furthermore, Western blot analysis suggested that c-Jun and Fos-related antigens rather than c-Fos per se were components of an ENKCRE-2/AP-1 complex. Thus, Fos-related proteins apparently form a complex with c-Jun that transactivates the proenkephalin gene.
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PMID:Regulation of the expression of proenkephalin mRNA in bovine adrenal chromaffin cells: Role of proto-oncogenes. 1991 94


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