Effect of acute ozone exposure on the proteinase—Antiproteinase balance in the rat lung

Pickrell, John; Gregory, R.E.; Cole, D. J. A.; Hahn, Fletcher F.; Henderson, Rogene F.

doi:10.1016/0014-4800(87)90063-3

Cited by 14 publications

(5 citation statements)

References 21 publications

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“…Both MMP-12 and elastin fragments generated by MMP-12 may contribute to the accumulation of macrophages and the pathogenesis of cigarette smoke-induced emphysema (16,21). Although we did not measure antiprotease expression in the lungs of ozone-exposed mice, a previous study has shown that ozone exposure induces a 35-80% decrease in antiprotease activity in lung tissue (39), which would be another factor contributing to emphysema. In the cigarette smoke exposure model, neutrophil recruitment occurs immediately following the beginning of tobacco smoke exposure and is followed by accumulation of macrophages; the early influx of neutrophils is paralleled by connective tissue breakdown, with an increase in elastin and collagen degradation that can be prevented by pretreatment with a neutrophil antibody or ␣ 1 -antitrypsin (11).…”

Section: L695 Ozone Exposure and Emphysemamentioning

confidence: 76%

A model of chronic inflammation and pulmonary emphysema after multiple ozone exposures in mice

Triantaphyllopoulos

Hussain

Pinart

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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Oxidative stress plays a role in the pathophysiology of emphysema through the activation of tissue proteases and apoptosis. We examined the effects of ozone exposure by exposing BALB/c mice to either a single 3-h exposure or multiple exposures over 3 or 6 wk, with two 3-h exposures per week. Compared with air-exposed mice, the increase in neutrophils in bronchoalveolar lavage fluid and lung inflammation index was greatest in mice exposed for 3 and 6 wk. Lung volumes were increased in 3- and 6-wk-exposed mice but not in single-exposed. Alveolar space and mean linear intercept were increased in 6- but not 3-wk-exposed mice. Caspase-3 and apoptosis protease activating factor-1 immunoreactivity was increased in the airway and alveolar epithelium and macrophages of 3- and 6-wk-exposed mice. Interleukin-13, keratinocyte chemoattractant, caspase-3, and IFN-γ mRNA were increased in the 6-wk-exposed group, but heme oxygenase-1 (HO-1) mRNA decreased. matrix metalloproteinase-12 (MMP-12) and caspase-3 protein expression increased in lungs of 6-wk-exposed mice. Collagen area increased and epithelial area decreased in airway wall at 3- and 6-wk exposure. Exposure of mice to ozone for 6 wk induced a chronic inflammatory process, with alveolar enlargement and damage linked to epithelial apoptosis and increased protease expression.

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Section: L695 Ozone Exposure and Emphysemamentioning

confidence: 76%

A model of chronic inflammation and pulmonary emphysema after multiple ozone exposures in mice

Triantaphyllopoulos

Hussain

Pinart

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…It is known that oxidative mechanisms may augment the activity of proteolytic enzymes, perhaps through inhibition of specific inhibitors (47,48). Therefore, to further examine possible mechanisms in addition to those associated with altered collagen and elastin metabolism in aortic disease, we determined the concentrations of co-factors involved both in free radical reactions and connective tissue metabolism.…”

Section: Discussionmentioning

confidence: 99%

Effects of Hypertension on Aortic Antioxidant Status in Human Abdominal Aneurysmal and Occlusive Disease

Hunter

Dubick

Keen

et al. 1991

Experimental Biology and Medicine

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The biochemical mechanisms by which hypertension accelerates atherosclerosis and increases the risk of aortic aneurysm rupture are poorly understood. This study evaluates the effects of hypertension on aortic trace element concentrations and antioxidant status in tissue removed from 26 normotensive (NT) and 20 hypertensive (HT) patients. Twenty-seven of 46 patients (59%) had aneurysmal (AA), and 19 of 46 (41%) had occlusive disease (OD). Aortic iron concentrations were markedly higher in both OD and AA tissue compared with controls. A similar trend was observed with copper concentrations, with the highest elevations observed in HT AA tissues. No significant differences were observed in zinc concentrations, except that HT AA aorta had significantly lower zinc levels than either OD or control tissue. Aortic ascorbic acid concentrations in diseased aorta were lower than those of controls, but independent of blood pressure. Copper-zinc-superoxide dismutase activity was similarly reduced, with the lowest activity observed in diseased aorta from HT patients. Only HT AA aorta had significantly higher manganese-superoxide dismutase activity than controls. The aortas of patients with AA had significantly lower amounts of elastin and greater elastase activity than either controls or those with OD. However, the differences were independent of blood pressure. Hypertensive patients with OD and AA had 31% more and 27% less aortic collagen, respectively, than their NT counterparts (P less than 0.05). These data suggest that the reduction in aortic collagen and elastin in HT patients with AA compared with their NT counterparts may explain the larger size of aneurysms and predispose to their eventual rupture. Furthermore, the diminished antioxidant status associated with HT predisposes to lipid peroxidation, which contributes to the acceleration of these processes. Our studies were conducted in patients with established aortic aneurysmal and occlusive disease. Whether these observations are pertinent to the pathogenesis of AA and OD remains unclear and merits further study.

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“…It is interesting that although trypsin is made in the pancreas and used in the intestine, and alpha-1 anti-trypsin (A1AT) is made in the liver, both trypsin and A1AT are also present in the serum at significantly high levels (Hendstrom et al, 1996;Donato et al, 2012). Presumably trypsin and A1AT exist in some sort of delicate balance, and the existence of such a balance has been proposed (Pickrell, 1987), in respect of mechanisms explaining why deficiencies, as well as excesses, in the amounts of either of these proteins lead to different diseases (Qing-quan et al, 2013). There is also evidence suggesting that trypsin is associated with cell proliferation (Ohta, 2003) and with certain cancers (Darmoul et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Sustained exposure to trypsin causes cells to transition into a state of reversible stemness that is amenable to transdifferentiation

Sharma

Kumar

Sharma

et al. 2019

Preprint

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During cell culture, trypsin, a serine protease, is applied to cells for 5-10 minutes to separate them from each other and from the underlying substratum so that they can be transferred to a different vessel, for re-plating, after growth medium containing 10 % serum has been added to the cells, in a well-known technique known as 'passaging'. The serum in the growth medium contains alpha-1 antitrypsin, which is a potent inhibitor of trypsin, elastase and other serine proteases.Although what is used is bovine serum in which levels of proteins could be different from levels seen in humans, normal human serum contains A1AT (> 1 mg/ml; > ~18 µmol/L) as well as trypsin itself (< 460 ng/ml, or ~0.02 µmol/L), with the former in a ~900-fold molar excess over the latter. Thus, it may be assumed there is also enough A1AT in the bovine serum added during passaging, to neutralize the trypsin (~100 μM) present in the small volume of trypsin-EDTA solution used to separate cells. What are the consequences of not adding serum, when growth medium is added, or of maintaining cells for a few tens of hours in the presence of trypsin, in a serum-free growth medium? What does such sustained exposure to trypsin during cell culture do to cells? More generally, what are the responses of cells within an organism to the balance of trypsin and A1AT in the serum that bathes them constantly? We know that excesses and deficiencies in the levels of either trypsin or A1AT are associated with disease. We know that cellular metabolism can be influenced through signaling involving protease activated membrane GPCR receptors (PAR1-4). In particular, we know of a receptor called PAR2, which is specifically activated by trypsin, expressed by cells at baseline levels, and upregulated through some feedback involving trypsin-activation. We also know that cells at sites of injury or inflammation produce and secrete trypsin, and that this trypsin can act locally upon cells in a variety of ways, all of which have probably not yet been elucidated. Here, we show that sustained exposure to trypsin induces cells to de-differentiate into a stem-like state. We show that if serum is either not added at all, or added and then washed away (after confluency is attained), during cell culture, all cells exposed to exogenously-added trypsin undergo changes in morphology, transcriptome, secretome, and developmental potential, and transition into a state of stemness, in minimal essential medium (MEM). Regardless of their origins, i.e., independent of whether they are derived from primary cultures, cell lines or cancer cell lines, and regardless of the original cell type used, exposure to trypsin (~10 µM; ~250 µg/ml) at a concentration 10-fold lower than that used to separate cells during passaging (~100 μM), over a period of 24-48 hours, causes cells to (1) become rounded, (2) cluster together, (3) get arrested in the G0/G1 stage of the cell cycle, (4) display increased presence of 5-hydroxymethyl cytosine in their nuclei (indicative of reprogramming), (5) display increased...

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Effect of acute ozone exposure on the proteinase—Antiproteinase balance in the rat lung

Cited by 14 publications

References 21 publications

A model of chronic inflammation and pulmonary emphysema after multiple ozone exposures in mice

A model of chronic inflammation and pulmonary emphysema after multiple ozone exposures in mice

Effects of Hypertension on Aortic Antioxidant Status in Human Abdominal Aneurysmal and Occlusive Disease

Sustained exposure to trypsin causes cells to transition into a state of reversible stemness that is amenable to transdifferentiation

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