Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tadpole collagenase (EC 3.4.24.3) cleaved chick cranial bone procollagen into two triple-stranded fragments, PCA and PCB. Only PCB, with an estimated molecular weight of about 60,000 for each component chain after reduction, was found to contain interchain disulfide bonds. The analogous cleavage of collagen is known to produce a large NH2-terminal fragment with a molecular weight of 70,000 for each chain and a small COOH-terminal fragment containing chains of about 25,000 molecular weight. Since PCB was too small to represent the product NH2-terminal to the site of collagenase cleavage, localization of interchain disulfide bonds to a COOH-terminal domain in procollagen was indicated. This assignment was conformed by Dintzis-type short-term labeling experiments. Procollagen obtained by acid extraction of bone lacked the COOH-terminal disulfide-bonded domain. The findings support a model for procollagen consisting of three proalpha chains each containing nonhelical NH2-terminal extensions of 20,000 molecular weight and COOH-terminal extensions of about 35,000 molecular weight, the latter linked by interchani disulfide bonds.
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PMID:Interchain disulfide bonds in procollagen are located in a large nontriple-helical COOH-terminal domain. 17 50

The induction of aryl hydrocarbon hydroxylase (AHH) by Aroclor 1254, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other polychlorinated organic compounds was examined in primary cultures of adult rat hepatocytes isolated by a collagenase perfusion technique. Following exposure of fresh hepatocyte cultures to 1 microgram/ml Aroclor 1254, AHH induction was undetected for 48 hr and then increased dramatically up to 96 hr. Cultures maintained in control medium for either 24, 48, or 72 hr prior to a 24-hr exposure to Aroclor 1254 displayed significant inducible AHH which was sustained to 96 hr. AHH induction was extremely sensitive to two planar polyaromatic hydrocarbons, 2,3,7,8-TCDD and 2,3,7,8-tetrachlorodibenzofuran, and the PCB congener 3,4,3',4'-tetrachlorobiphenyl, but insensitive to 2,6-dichlorodibenzofuran, 2,5,2',5'-tetrachlorobiphenyl, 2,4,5,2',4',5'-hexachlorobiphenyl, and hexachlorobenzene. The induction of AHH activity in primary cultures of adult rat hepatocytes may represent a useful bioassay for screening extracts of foodstuffs, biological fluids, or environmental samples for dioxin-like activity.
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PMID:Aryl hydrocarbon hydroxylase induction in adult rat hepatocytes in primary culture by several chlorinated aromatic hydrocarbons including 2,3,7,8-tetrachlorodibenzo-p-dioxin. 404 93

It was previously reported that in vivo exposure of fish to combined aryl hydrocarbon receptor agonist (AhR; 3,3',4,4'-tetrachlorobiphenyl, PCB-77) and estrogen receptor agonist (ER; nonylphenol, NP) resulted in potentiation and inhibition (depending on dose ratio, sequential order of exposure, and seasonal changes) of NP-induced responses by PCB-77. The experiments described in this report extend this study by testing whether the effects of PCB-77 on NP-induced ER signaling are mediated through AhR-induced transcriptional suppression of target genes. Trout hepatocytes were isolated by a two-step collagenase perfusion method. After 48-h culture, hepatocytes were exposed to 5 or 10 microM nonylphenol (NP) singly and in combination with PCB-77 at 0.1, 1, and 10 microM. Cells were harvested after 96-h exposure and processed for RNA isolation. Gene expression patterns were quantified using real-time polymerase chain reaction (PCR) with specific primer sets and by Northern blot. Exposure of cells to NP caused significant elevation of ERalpha, ERbeta, Vtg, and Zrp mRNA expressions, while combined exposure with PCB-77 concentration inhibited NP-induced ERs and their target gene expressions. Exposure of trout hepatocytes to PCB-77 alone caused a rapid induction of cytochrome P-450 (CYP) 1A1 mRNA, and combined exposure with NP caused significant reduction in PCB-77 induced CYP1A1 gene expression. Exposure of cells to PCB-77 concentrations induced significant reduction in AhRalpha mRNA (except 1 microM PCB-77, which caused the induction of AhRalpha mRNA levels). AhRbeta mRNA levels in the cells were inhibited after 96-h exposure to PCB-77, while combined exposure with 5 microM NP restored the PCB-77-inhibited AhRbeta mRNA levels to baseline. Taken together, the overall results in this study show that PCB-77 suppresses the gene expression of the ERs and their target genes by transcription mechanism(s). The roles of AhRs in mediating these responses seem to involve the ligand-activated AhR transcriptional induction of CYP1A1. In addition to their frequently described functions as activators of metabolic potentiation and detoxification of various foreign chemicals, data presented in the present study point to other endogenous functions of AhRs that need to be studied further.
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PMID:Gene expression patterns in estrogen (nonylphenol) and aryl hydrocarbon receptor agonists (PCB-77) interaction using rainbow trout (Oncorhynchus Mykiss) primary hepatocyte culture. 1629 59