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

Collagen which is present in the myocardium in relatively small amounts is the most abundant structural protein of the connective tissue network. Its structural organization consists of a complex weave of collagen fibers that surrounds and interconnects myocytes, groups of myocytes, muscle fibers and muscle bundles. The conformation of interstitial fibrillar collagen makes it highly resistant to degradation by all proteinases other than specific collagenases. In hearts with myocardial damage secondary to myocardial infarction, chronic ischemia, inflammation, or cardiomyopathy, a complex sequence of compensatory events occur that eventually result in an adverse left ventricular remodeling. This continual state of remodeling is characterized by persistent collagenase activity, fibrillar collagen degradation, and progressive myocyte loss. The net effect is a shift in the balance between collagen synthesis and degradation which leads to an inadequate fibrillar collagen matrix, progressive ventricular dilatation and sphericalization with wall thinning and eventual congestive heart failure.
 ...
PMID:Ventricular remodeling in heart failure: the role of myocardial collagen. 854 Apr 1

Adult mammalian ventricular myocytes are terminally differentiated cells, and the prevailing perception has been that DNA synthesis and repair are not active. We tested the hypothesis that there is potential for DNA synthesis and repair by studying the ability of whole-cell extracts from adult myocytes to incorporate [alpha-32P]dCTP into damaged plasmids. Left ventricular myocytes were isolated from adult cat hearts by collagenase dissociation. Cells were maintained in room air (control extract, CE) or made ischemic (IE) with N2 displacement of O2 and extracted for total protein. The nicked form of the plasmid was produced by exposure to an Fe3+/ascorbic acid free radical generating system. Both IE and CE degraded the supercoiled form of the plasmid and incorporated [alpha-32P]dCTP into the nicked (32P/DNA mass; CE = 2.2, IE = 3.0) and linear forms (32P/DNA mass; CE = 28.7, IE = 25.2). Exposure of plasmids to UV light did not inhibit incorporation of label. Inhibition studies with the cell extracts suggested a participation of polymerase delta in myocyte DNA repair/synthesis. Myocyte extract was as active as extract from rapidly growing COS cells at incorporating labeled nucleotides into plasmid DNA. The ability of intact myocytes to incorporate [alpha-32P]dCTP into endogenous DNA was measured in isolated cells made permeable with saponin. Studies were done in room air or N2. Permeable cells incorporated [alpha-32P]dCTP into nuclear DNA, but maximal specific activity of DNA was observed at 15 minutes with ischemia and at 60 minutes with room air control cells (ischemia, 1.34 +/- 0.5, 0.86 +/- 0.33, 0.60 +/- 0.04; air, 1.0, 1.28 +/- 0.20, 1.87 +/- 0.38, at 15, 30, and 60 minutes, respectively). These data indicate that mammalian adult ventricular myocytes can actively repair and/or synthesize both exogenous and endogenous DNA. A DNA synthetic response to cellular damage may have important pathological and clinical implications.
 ...
PMID:DNA synthesis in adult feline ventricular myocytes. Comparison of hypoxic and normoxic states. 857 73

Clinical approaches to the diagnosis of PTL and the prediction of PTD are complicated by the absence of a gold standard for the pathogenic process leading to PTD. There is also substantial overlap between the signs and symptoms of PTL and impending PTD, and the normal processes of pregnancies destined to remain uncomplicated (e.g., our inability to convincingly differentiate PTL from Braxton-Hicks contractions). Our emphasis on the diagnosis of PTL rather than the pathogenic process preceding PTD also results in failure to detect the 50% of spontaneous PTDs in which uterine contractions follow PPROM. Thus, clinical predictors of incipient PTD including cervical change, uterine contractions, vaginal bleeding, risk scoring schemes, and fetal breathing activity, either have poor sensitivity or specificity, or are accurate only at late stages in the pathogenic process. The most promising approaches to the detection of impending PTD are laboratory indices of the putative pathogenic processes including: maternal serum or plasma CRH, salivary E3, serum collagenase and cervicovaginal cytokines, granulocyte elastase, and FFN levels. However, even if these indices prove sensitive, specific, and early predictors of PTD, they will be useful only if more appropriate therapies are found to treat patients. The latter will depend on addressing the primary causes of chorionic-decidual cell activation (e.g., infection, stress, utero-placental ischemia, hemorrhage, endocrinopathies).
 ...
PMID:The diagnosis of preterm labor and the prediction of preterm delivery. 861 65

End organ ischemia, fragmentation of elastic membranes, and aneurysm formation in patients with giant cell vasculitis results from an inflammation destroying the mural layers of large and medium sized arteries. Although the inflammatory infiltrate extends through all layers of the affected blood vessel, the most pronounced changes involve the intima and the internal elastic lamina. Analysis of the functional profile of tissue infiltrating CD68+ cells demonstrates that different subsets of macrophages can be distinguished. TGFbeta1-expressing CD68+ cells coproduce IL-1beta and IL-6, are negative for inducible nitric oxide synthase (iNOS), and exhibit a strong preference for localization in the adventitia. The adventitial homing of TGFbeta1+ CD68+ cells places them in the vicinity of IFN-gamma secreting CD4+ T cells which also accumulate in the exterior layer of the artery. Conversely, iNOS expressing CD68+ cells are negative for TGFbeta and are almost exclusively found in the intimal layer of the inflamed artery. The intimal-medial junction is the preferred site for 72-kD collagenase expressing CD68+ cells. Thus, TGFbeta1-producing macrophages colocalize with activated CD4+ T cells and home to an area of inflammation which is distant from the site of tissue damage but critical in regulating cellular influx, suggesting that TGFbeta1 functions as a proinflammatory mediator in this disease. iNOS- and 72-kD collagenase-producing macrophages accumulate at the center of pathology implying a role of these products in tissue destruction. These data indicate that the microenvironment controls the topographical arrangement as well as the functional commitment of macrophages.
 ...
PMID:Correlation of the topographical arrangement and the functional pattern of tissue-infiltrating macrophages in giant cell arteritis. 883 14

Although heart attack is caused by occlusion of a major coronary artery, some patients have occlusion without heart attack because these patients have sufficient collateral circulation to provide an alternate pathway for blood supply to the myocardium at ischemic risk. The growth of new capillary vessels (angiogenesis) and enlargement of preexisting vessels play an important role in the collateral development. We evaluated the hypothesis that extracellular matrix metalloproteinase (MMP) expression is altered in coronary collateral arteries (0.5-1 mm o.d.) isolated from canine hearts 2-4 months after surgical placement of an ameroid occluder around the proximal left circumflex artery (n = 4), during the development of collateral vessels and restructuring new vessels. Histologic studies (hematoxylin and eosin, trichrome, and van Gieson stains) indicated cellular proliferation and increased collagen and elastin content in collateral vessels compared with comparable-sized unoccluded arterial segments of the left anterior descending (LAD) artery. In situ MMP activity of collateral vessels, measured using denatured collagen in the gel matrix, indicated an increase in total MMP activity in the intima of collateral vessels compared with normal LAD vessels. To further identify the type of MMP, tissue homogenates were prepared from collateral and LAD vessels and analyzed by SDS-PAGE zymography. The results suggest induction of gelatinase A and gelatinase B expression in collateral vessels compared with normal LAD tissue, when identical amounts of total protein were loaded onto each lane in the gel. Based on plasminogen-casein zymography, we observed the tissue plasminogen activator level to be increased in collateral vessels. On the basis of immunoblot and mRNA (Northern blot) analyses, we determined that the MMP-1 level was induced in collateral vessels 2 and 4 months after ameroid occlusion. In contrast with MMP-1, the level of TIMP-1 (tissue inhibitor of metelloproteinases) was decreased significantly (p < 0.001) in collateral compared with LAD vessels, suggesting a role for arterial TIMP in anti-angiogenic activity. Collectively, these results suggest that chronic occlusion of a major coronary artery induces upregulation of vascular remodeling mechanisms subserving collateral development. Increased MMP-2 activity in collaterals may be associated with decreased levels of tissue inhibitor of metalloproteinases and fibrous tissue remodeling following angiogenic and (or) adaptive responses of the myocardium to chronic ischemia.
 ...
PMID:Temporal expression of extracellular matrix metalloproteinases and tissue plasminogen activator in the development of collateral vessels in the canine model of coronary occlusion. 896 Mar 89

The present study evaluated the effect of the benzothiazepine Ca2+ channel blocker diltiazem (DZ) on altered hepatocellular Ca2+ regulation and oxidant injury during hemorrhagic shock/resuscitation. In anesthetized, male Sprague-Dawley rats, hemorrhagic shock was induced by rapid blood withdrawal and maintaining the mean arterial blood pressure at 40 mm Hg over 60 minutes. Rats were then resuscitated with 60% of shed blood and threefold the shed blood volume of Ringer's lactate. At the end of ischemia, and 60 or 300 minutes after resuscitation, hepatocytes were isolated by liver collagenase perfusion. Hepatocellular Ca2+ exchange (Ca2+ex), rate of cellular Ca2+ influx (Ca2+in), and Ca2+ membrane flux (Ca2+flux) were determined using 45Ca incubation techniques. Hepatocyte oxidant injury was evaluated by fluorometrically measuring thiobarbituric acid reactive substances and oxidized/reduced glutathione. Both hemorrhage and hemorrhage/resuscitation increased hepatocellular Ca2+in, Ca2+ex, and Ca2+flux. In contrast to control and sham-operated rats, in vitro stimulation by the Ca2+ agonist epinephrine (100 nmol/L) of hepatocytes from either hemorrhaged or resuscitated rats did not further increase Ca2+in. Administration of DZ (.8 mg/kg) with resuscitation significantly decreased cellular Ca2+ex and Ca2+flux, but did not restore impaired epinephrine-induced Ca2+in. DZ prevented hepatocyte lipid peroxidation and glutathione oxidation. These findings suggest hepatocellular Ca2+ overload and impaired Ca2+ signaling during hemorrhage/resuscitation. Increased Ca2+ uptake could be because of a receptor-gated Ca2+ influx and/or oxygen-free radical induced membrane Ca2+ leaks.
 ...
PMID:Altered hepatocellular Ca2+ regulation during hemorrhagic shock and resuscitation. 902 50

Chemical injuries of the eye may produce extensive damage to the ocular surface epithelium, cornea, and anterior segment, resulting in permanent unilateral or bilateral visual impairment. Pathophysiological events which may influence the final visual prognosis and which are amenable to therapeutic modulation include 1) ocular surface injury, repair, and differentiation, 2) corneal stromal matrix injury, repair and/or ulceration, and 3) corneal and stromal inflammation. Immediately following chemical injury, it is important to estimate and clinically grade the severity of limbal stem cell injury (by assessing the degree of limbal, conjunctival, and scleral ischemia and necrosis) and intraocular penetration of the noxious agent (by assessing clarity of the corneal stroma and anterior segment abnormalities). Immediate therapy is directed toward prompt irrigation and removal of any remaining reservoir of chemical contact with the eye. Initial medical therapy is directed promoting re-epithelialization and transdifferentiation of the ocular surface, augmenting corneal repair by supporting keratocyte collagen production and minimizing ulceration related to collagenase activity, and controlling inflammation. Early surgical therapy if indicated, is directed toward removal of necrotic corneal epithelium and conjunctiva, prompt re-establishment of an adequate limbal vascularity, and re-establishment of limbal stem cell population early in the clinical course, if sufficient evidence exists of complete limbal stem cell loss. Re-establishment of limbal stem cells by limbal autograft or allograft transplantation, or by transfer in conjunction with large diameter penetrating keratoplasty, may facilitate development of an intact, phenotypically correct corneal epithelium. Limbal stem cell transplantation may prevent the development of fibrovascular pannus or sterile corneal corneal ulceration, simplify visual rehabilitation, and improve the visual prognosis. Advances in ocular surface transplantation techniques which allow late attempts at visual rehabilitation of a scarred and vascularized cornea include limbal stem cell transplantation for incomplete transdifferentiation and persistent corneal epithelial dysfunction, and conjunctival and/or mucosal membrane transplantation for ocular surface mechanical dysfunction. Rehabilitation of the ocular surface may be followed, if necessary, by standard penetrating keratoplasty if all aspects of ocular surface rehabilitation are complete, or by large diameter penetrating keratoplasty if successful limbal stem cell transplantation cannot be achieved but other ocular surface rehabilitation is complete.
 ...
PMID:Chemical injuries of the eye: current concepts in pathophysiology and therapy. 910 67

The present study was undertaken to ascertain the role of smooth muscles and pericytes in the microcirculation during hyperperfusion and hypoperfusion following ischemia in rats. Paired external carotids, the pterygopalatine branch of the internal carotids and the basilar artery were exposed and divided. Reversible inflatable occluders were placed around the common carotids. After 24 h, the unanesthetized rat underwent 10-min ischemia by inflating the occluders. Continuous cortical cerebral blood flow (c-CBF) was monitored by laser Doppler flowmetry. The measured c-CBF was below 20% of control (P < 0.001) during ischemia. A c-CBF of 227.5 +/- 54.1% (P < 0.001) was obtained during reperfusion hyperemia. A c-CBF of 59.7 +/- 8.8% (P < 0.001) occurred at the nadir of postischemic hypoperfusion, and this was followed by a second hyperemia. The cytoarchitecture of the vascular smooth muscles and pericytes was assessed by scanning electron microscopy. Samples were prepared using a KOH-collagenase digestion method. In control rats, arteriolar muscle cells showed smooth surfaces. Capillary pericytes were closely apposed to the endothelium. Immediately after reperfusion, transverse membrane creases were observed on the smooth muscle surfaces. During maximal hyperemia the creases disappeared. When c-CBF started to decrease the creases became visible again. Throughout the postischemic hypoperfusion the creases remained. Capillary endothelial walls became tortuous in the late phase of hypoperfusion. During the second hyperemia most arteriolar muscle cells showed smooth surfaces. Some pericytes appeared to have migrated from the vascular wall. The morphological changes of smooth muscle membranes suggest that they are related to specific perfusional disturbances during ischemia and reperfusion.
 ...
PMID:Cerebral cortex blood flow and vascular smooth muscle contractility in a rat model of ischemia: a correlative laser Doppler flowmetric and scanning electron microscopic study. 911 1

Enzymatic digestion of donor pancreases is a vital step in human and large mammalian islet isolation. The variable enzymatic activities of different batches of commercially available collagenase is a major obstacle in achieving reproducibility in islet isolation procedures. In the present work, the effectiveness of Liberase, a standardized mixture of highly purified enzymes recently developed for the separation of human islets, was compared with that of a traditional collagenase preparation (type P). The results of 50 islet isolations using Liberase enzyme were compared with those of 36 isolations with collagenase, type P. No significant differences in donor age, cold ischemia time, digestion time, or weight of the pancreases were observed between the two groups. Islet yield was significantly higher in the group where the Liberase enzyme was used. All parameters examined (islet number, islet number per gram of tissue, islet equivalent number, and islet equivalent number per gram of tissue) were significantly improved when Liberase enzyme was used. Different lots of Liberase enzyme were tested, and no difference was observed. Islets isolated with Liberase enzyme were also of larger size and were much less fragmented, suggesting a gentler enzymatic action and better preservation of anatomical integrity. Islets isolated with Liberase enzyme, assessed both in vitro and in vivo, revealed a functional profile similar to that of islets separated with collagenase. Liberase enzyme appears, therefore, to represent a new powerful tool for improving the quality of human islet isolation.
 ...
PMID:Improved human islet isolation using a new enzyme blend, liberase. 920 Jun 45

The mitochondrial respiratory parameters were measured in situ, i.e. in saponin-skinned rabbit cardiac fibers and in fibers treated with saponin + collagenase. It was found that the decrease of maximal ADP-stimulated respiration rate of saponin-skinned fibers with pyruvate + malate under the conditions of total ischemia (0.5-1.5 h) is less pronounced as compared to isolated mitochondria. Maximal succinate oxidation rate (+ADP), however, was not different from control (1 h ischemia) but it exceeded the control level when measured in the medium supplemented with cytochrome c. It was also demonstrated that treatment of fibers with collagenase alone or in combination with saponin significantly (almost 2 fold) enhanced the maximal ADP-stimulated respiration rate if compared with saponin-skinned fibers. The data obtained suggest that mitochondrial respiration in saponin-skinned rabbit cardiac fibers is not completely revealed, most probably, due to insufficient permeabilization of sarcolemma by saponin and, thus, inadequate accessibility of mitochondria to exogenous substrates, ADP in particular. These parameters can be improved by pre-treatment of fibers with collagenase.
 ...
PMID:The effects of ischemia and experimental conditions on the respiration rate of cardiac fibers. 930 70


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>