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Query: UNIPROT:P06889 (Mol)
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In this study, we examined the sequential expression of several matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and growth factors as well as the presence of apoptosis in a model of pulmonary fibrosis induced in rats with paraquat and hyperoxia. Animals showing neither clinical nor morphological changes with this double aggression were classified as "resistant". Rats were killed at 1, 2, 3, and 6 wk, and lungs were used for collagen content, gene expression by real-time PCR, gelatinolytic activity by zymography, apoptosis by in situ DNA fragmentation, and protein localization by immunohistochemistry. Our results showed a significant decrease of collagenases MMP-8 and MMP-13, with an increase of TIMP-1 and transforming growth factor-beta. Immunoreactive TIMP-1 was increased in experimental rats and primarily localized in alveolar macrophages. Expression of gelatinases MMP-2 and MMP-9 mRNAs was not affected, but lung zymography revealed an increase in progelatinase B, progelatinase A, and its active form. Epithelial apoptosis was evident from the first week, whereas at later periods, interstitial cell apoptosis was also noticed. Resistant animals behave as controls. These findings suggest that an imbalance between collagenases and TIMPs, excessive gelatinolytic activity, and epithelial apoptosis participate in the fibrotic response in this experimental model.
Am J Physiol Lung Cell Mol Physiol 2003 Nov
PMID:Unbalanced collagenases/TIMP-1 expression and epithelial apoptosis in experimental lung fibrosis. 1288 63

The matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) have been associated with ovarian tissue remodelling and development of ovarian tumours. With respect to ovarian cancer, the majority of previous studies were performed on serous and mucinous tumours, and little is known about clear cell carcinoma, which shows unique characteristics among ovarian cancers. In the present study, we assessed the differences in the levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 in the normal ovary and ovarian tumours of different histology, including clear cell carcinoma, using specific enzyme-linked immunosorbent assays. In malignant tumours, a prominent increase in pro-MMP-9 levels was observed compared with those of normal ovary and benign tumours, and pro-MMP-2 and TIMP-1 levels were moderately increased. In contrast, TIMP-2 levels were markedly decreased in malignant tumours compared with normal ovary with the exception of clear cell carcinoma, in which they were significantly elevated. Similar results were obtained by the organ culture of carcinoma tissue and normal ovary as well as in the cyst fluids of the tumours. Increased expression of TIMP-2 in clear cell carcinoma was also confirmed by Western blot analysis. Immunohistochemistry showed that TIMP-2 immunoreactivity was localized predominantly in epithelial cancer cells in clear cell carcinoma, while it was present mainly in stromal cells in the other histological types. Taken together, the present study shows that TIMP-2 expression is markedly increased in clear cell carcinoma of the ovary, suggesting a role of TIMP-2 in its unique characteristics among ovarian cancers.
Mol Hum Reprod 2003 Oct
PMID:Increased expression of tissue inhibitor of metalloproteinase-2 in clear cell carcinoma of the ovary. 1297 Mar 94

This study evaluated the effects of season and spatial distribution on the fatty acid composition of Patella depressa gonads and Patella spp. soft body tissue. The results show that the quantitatively most important fatty acids were the saturated fatty acids (SFA) 16:0, 14:0 and 18:0; the monounsaturated fatty acids (MUFA) 18:1(n-7), 18:1(n-9), 16:1(n-7) and 20:1(n-9) and the polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA 20:5(n-3)), and arachidonic acid (ARA 20:4(n-6)). P. depressa and P. ulyssiponensis soft body fatty acid profiles revealed significant differences between sexes; males showed significantly higher percentages of PUFA, highly unsaturated fatty acids (HUFA), (n-3) fatty acids and ARA, while in females significantly higher proportions of MUFA were found. Analysis of variance on the fatty acid composition of P. depressa gonads revealed significant differences between sexes, which were more marked than when the whole body was analysed. Males showed a significantly higher percentage of PUFA, HUFA, fatty acids from the (n-3) and (n-6) series, ARA and EPA, while females were seen to have higher proportions of SFA, MUFA and total fatty acid methyl esters (FAME). Some variability was seen to occur due to shore location and seasons, but these effects were not so obvious.
Comp Biochem Physiol B Biochem Mol Biol 2003 Nov
PMID:Spatial and temporal variation of the fatty acid composition of Patella spp. (Gastropoda: Prosobranchia) soft bodies and gonads. 1460 51

Matrix metalloproteinases (MMPs) are an at least 23 member family of calcium and zinc dependent enzymes implicated in many physiological and pathological processes. Asthma, chronic obstructive pulmonary disease (COPD) and emphysema are diseases associated with an inflammation of the airways and lung parenchyma. In this review, we focus on the role played by MMPs in the pathogenesis of inflammation, airway remodelling and alveolar destruction, depicting the observational studies in humans and the experimental studies in animal models. During the course of asthma, MMP-2,-8,-9 and TIMP-1 are expressed at baseline and the allergen exposure or exacerbations of the disease lead to an increase of MMP-9 secretion being at this time much higher than that of TIMP-1, allowing temporarily a matrix damage, possibly followed by abnormal repair. Animal models suggest a predominant role for MMP-9 and MMP-12 in the pathogenesis of pulmonary inflammation and link an absence of MMP-2 to an increased parenchymal inflammation. In COPD and emphysema, human studies indicate an over-secretion of MMP-2,-8,-9 and animal models pointout MMP-1 and MMP-12 as being key players in the pathogenesis of emphysema. Taken together, these data identify specific MMP inhibition as appropriate target for therapeutic intervention in asthma or COPD/emphysema They also strongly argue against the widespread use of large spectrum non specific inhibitors that could be detrimental.
Cell Mol Biol (Noisy-le-grand) 2003 Sep
PMID:Pathogenic role of matrix metalloproteases and their inhibitors in asthma and chronic obstructive pulmonary disease and therapeutic relevance of matrix metalloproteases inhibitors. 1465 45

Membrane-type matrix metalloproteinases (MT-MMPs) have attracted strong attention, because four of them can activate a key player in the tumor scenario, proMMP-2/progelatinase A. In addition to this indirect effect on the cellular environment, these MT-MMPs degrade extracellular matrix proteins, and their overproduction is associated with tumor growth. We have solved the structure of the catalytic domain (cd) of MT3-MMP/MMP-16 in complex with the hydroxamic acid inhibitor batimastat. CdMT3-MMP exhibits a classical MMP-fold with similarity to MT1-MMP. Nevertheless, it also shows unique properties such as a modified MT-specific loop and a closed S1' specificity pocket, which might help to design specific inhibitors. Some MT-MMP-specific features, derived from the crystal structures of MT-1-MMP determined previously and MT3-MMP, and revealed in recent mutagenesis experiments, explain the impaired interaction of the MT-MMPs with TIMP-1. Docking experiments with proMMP-2 show some exposed loops including the MT-loop of cdMT3-MMP involved in the interaction with the proMMP-2 prodomain in the activation encounter complex. This model might help to understand the experimentally proven importance of the MT-loop for the activation of proMMP-2.
J Mol Biol 2004 Feb 06
PMID:Crystal structure of the catalytic domain of MMP-16/MT3-MMP: characterization of MT-MMP specific features. 1474 Dec 17

The maternal aorta undergoes substantial functional and structural adaptation in pregnancy. Both aortic diameter and compliance are increased and studies of animal and human gestation indicate that these changes are initiated in early pregnancy and maintained until delivery. The mechanisms underlying aortic adaptation in normal pregnancy remain largely unknown but matrix metalloproteinase enzymes (MMP) are likely to play a key role. Gene expression of candidate MMP and specific tissue inhibitors of MMP (TIMP) were investigated in non-pregnant, pregnant (days 7, 14, 21) and postpartum (day 7) rat aorta using real-time PCR. Of the gene transcripts studied (MMP-2, -3, -7, -9, -12, -13, MT1MMP, TIMP-1, -2) in rat aorta, only MMP-3 was significantly elevated with a 24-fold increase observed in late gestation compared to virgin control (P = 0.0001). MMP-2 mRNA appeared constitutively expressed and unchanged at time-points studied, but MMP-2 activity as assessed by gelatin zymography suggested further modulation after transcription and/or post-translation in rat aorta with activity increased in early pregnancy (P < 0.01, compared to virgin control). These data suggest that MMP-2 and MMP-3 may contribute to adaptive processes in the maternal rat aorta at different gestations and further support a role for this family of enzymes in physiological vascular remodelling.
Mol Hum Reprod 2004 May
PMID:Aortic adaptation to pregnancy: elevated expression of matrix metalloproteinases-2 and -3 in rat gestation. 1504

Manufactured gas plant residue (MGP) is a complex mixture of polycyclic aromatic hydrocarbons (PAHs) that is tumorigenic in the lungs of mice. This study compared the relative genotoxicity of 7H-benzo[c]fluorene (BC), a PAH component of MGP, with MGP and MGP fractions in order to assess the contribution of BC to the genotoxicity of MGP. An MGP sample was separated into seven fractions (F1-F7) using silica gel column chromatography with petroleum ether (PE) followed by PE:acetone (99:1 v/v, then 98:2). PAHs were quantified using gas chromatography/mass spectrometry. An aliquot of F2, the fraction with the highest BC concentration and highest weighted mutagenic activity in Salmonella typhimurium strain TA98, was further separated using silica gel thin-layer chromatography with hexane. The first F2 subfraction, sF2-a, was enriched in BC and coeluting compounds and contained 35,000 ppm BC and 216,109 ppm carcinogenic PAHs (cPAHs, the sum of seven PAHs categorized by the U.S. EPA as class B2 carcinogens). The second F2 subfraction, sF2-b, contained a ninefold lower concentration of BC, with 3,900 ppm BC and 45,216 ppm cPAHs. Female ICR mice received topical application of crude MGP, crude MGP spiked with analytical-grade BC, F2, sF2-a, sF2-b, or analytical-grade BC. DNA adduct levels were analyzed by nuclease P1-enhanced (32)P-postlabeling. In lung DNA of mice receiving 0.48 or 3.0 mg/mouse, net total RAL x 10(9) values were F2, 30.8 and 87.2; sF2-a, 24.8 and 106.7; and sF2-b, 19.6 and 151.0, respectively. Mice dosed with 0.10 mg analytical-grade BC (the mass of BC in 3.0 mg sF2-a) exhibited a net total RAL x 10(9) value of 7.03 in lung DNA. This was equal to approximately 7% of the total RAL x 10(9) value produced by 3.0 mg sF2-a. Thus, although BC appears to make an appreciable contribution to pulmonary adduct formation, the results suggest that MGP components other than BC play an important role in lung DNA adduct formation following topical MGP administration.
Environ Mol Mutagen 2004
PMID:Comparative in vitro and in vivo genotoxicities of 7H-benzo[c]fluorene, manufactured gas plant residue (MGP), and MGP fractions. 1506 3

Total lipids (TL), lipid classes, and their associated fatty acids from muscle and liver of captive and wild mature female broodstocks were investigated in order to estimate the fatty acid requirements of white seabream (Diplodus sargus). The results showed that the percentage of triacylglycerol was higher in liver and muscle of captive fish than in wild fish. The distribution of phospholipid classes in liver and muscle of both fish groups was similar, phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol being the predominant lipid classes. The general pattern of fatty acid distribution in total lipid of liver and muscle from captive and wild fish was similar. However, the relative percentage of specific fatty acids differed in captive and wild fish. The most noteworthy difference was the lower proportion of arachidonic acid (20:4n-6, AA) and the higher proportion of eicosapentaenoic acid (20:5n-3, EPA) in liver and muscle of captive fish with respect to those of wild fish. The proportion of docosahexaenoic acid (22:6n-3, DHA) did not differ between the two fish groups. The differences in EPA and AA proportions between captive and wild fish implied that captive fish presented a higher EPA/AA ratio and a lower DHA/EPA ratio than wild fish. In general terms, in both liver and muscle, the differences in fatty acid composition observed for TL were extended to all lipid classes. The results suggest that the different AA, EPA and DHA proportions in liver and muscle between captive and wild broodstocks are attributed to different levels of these fatty acids in broodstock diets.
Comp Biochem Physiol B Biochem Mol Biol 2004 May
PMID:Lipid and fatty acid composition of muscle and liver from wild and captive mature female broodstocks of white seabream, Diplodus sargus. 1514 40

Consumption of contaminated water has been implicated as a major source of Cryptosporidium infection in various outbreak investigations and case control studies. Surveys conducted in various regions of the United States demonstrated the presence of Cryptosporidium oocysts in 67-100% of wastewaters, 24-100% of surface waters, and 17-26.8% of drinking waters. The identity and human infective potential of these waterborne oocysts are not known, although it is likely that not all oocysts are from human-infecting Cryptosporidium species. Likewise, the source of the oocyst contamination is also not fully clear. Farm animals and human sewage discharge are generally considered to be the major sources of surface water contamination with C. parvum. Because Cryptosporidium infection is common in wildlife, it is conceivable that wildlife can also be a source for Cryptosporidium oocysts in waters. The presence of host-adapted Cryptosporidium spp. and genotypes makes it possible to develop molecular tools to assess the human infection potential and source of Cryptosporidium oocysts in water.Currently, the identification of Cryptosporidium oocysts in environmental samples is largely made by the use of immunofluorescent assay (IFA) after concentration processes (Environmental Protection Agency [EPA] recommended information collection rule [ICR] method or method 1622/1623 or similar techniques). Because IFA detects oocysts from all Cryptosporidium parasites, the species distribution of Cryptosporidium parasites in environmental samples cannot be assessed. Although many surface water samples contain Cryptosporidium oocysts, it is unlikely that all these oocysts are from human-pathogenic species or genotypes, because only five genotypes of Cryptosporidium parasites (the C. parvum human and bovine genotypes, C. meleagridis, C. canis, and C. felis) are responsible for most human infections. Information on the source of C. parvum contamination is necessary for effective evaluation and selection of management practices for reducing C. parvum contamination of surface water and the risk of cryptosporidiosis. Thus, identification of oocysts to species and genotype levels is of public health importance.
Methods Mol Biol 2004
PMID:Detection and differentiation of Cryptosporidium oocysts in water by PCR-RFLP. 1515 28

The US population is located in a wide range of latitudes, longitudes, and altitudes over mainland United States. Subsequently, high UV irradiants are found at southern locales, whilst in some northern areas, particularly at high latitudes, insufficient levels of ambient UV radiation to synthesize pre Vitamin D in humans are reported. This fact, coupled with the cold northern climates (resulting in high amounts of skin covered in clothing), some people may be susceptible to hypovitaminosis D. Surprisingly, hypovitaminosis D is still relatively common in developed countries such as the USA and the UK. In a large epidemiologically based study of 15,778 noninstitutionalized adult men and women living in the US, 9% had low serum 25-hydroxyvitamin D levels (15 ng/ml) [N. Engl. J. Med. 339 (1998) 12]. Further evidence of this came from recent research by McGrath [Med. Hypertens. 56 (2001) 367] who found that adults living in South East Queensland (with Queensland known as having the highest rates of skin cancer in the world) have surprisingly high rates of Vitamin D deficiency and insufficiency (8 and 23%, respectively). Therefore, hypovitaminosis D represents a serious issue for public health in both sunny and cold climates. This paper will present data on the distribution of Vitamin D forming UV over the USA using collected spectrally resolved ambient UV data from the US EPA Brewer spectrometer UV Monitoring Network. This data is obtained from the network of 21 Brewer spectrometers deployed throughout the USA, allowing for investigation of changes in Vitamin D producing UV with season and location.
J Steroid Biochem Mol Biol 2004 May
PMID:The climatology of Vitamin D producing ultraviolet radiation over the United States. 1522 24


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