Induction of arginase isoforms in the lung during hyperoxia

Que, Loretta G.; Kantrow, Stephen P.; Jenkinson, Christopher P.; Piantadosi, Claude A.; Huang, Y.-C. T.

doi:10.1152/ajplung.1998.275.1.l96

Cited by 82 publications

(107 citation statements)

References 19 publications

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“…In the newborn rat, we (5) have previously reported that chronic hyperoxia induces pulmonary hypertension. Hyperoxia is known to upregulate arginase expression in lung (29) and possibly contributed to decreased NO production that we reported in this newborn model of pulmonary hypertension (5).…”

Section: Discussionsupporting

confidence: 53%

Developmental changes in arginase expression and activity in the lung

Belik

Shehnaz²,

Pan³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Arginases compete with nitric oxide (NO) synthases for L-arginine as common substrate. Pulmonary vascular and airway diseases in which arginase activity is increased are associated with decreased NO production and reduced smooth muscle relaxation. The developmental patterns of arginase activity and type I and II isoforms expression in the lung have not been previously evaluated. Hypothesizing that lung arginase activity is developmentally regulated and highest in the fetus, we measured the expression of both arginase isoforms and total arginase activity in fetal, newborn, and adult rat lung, pulmonary artery, and bronchial tissue. In addition, intrapulmonary arterial muscle force generation was evaluated in the absence and presence of the arginase inhibitor N -hydroxy-nor-L-arginine (nor-NOHA). Arginase II content, as well as total arginase activity, was highest in fetal rat lung, bronchi, and pulmonary arterial tissue and decreased with age (P Ͻ 0.05), and its lung cell expression was developmentally regulated. In the presence of nor-NOHA, pulmonary arterial force generation was significantly reduced in fetus and newborn (P Ͻ 0.01). No significant change in force generation was noted in bronchial tissue following arginase inhibition. In conclusion, arginase II is regulated developmentally, and both expression and activity are maximal during fetal life. We speculate that the maintenance of a high pulmonary vascular resistance and decreased lung NO production prenatally may, in part, be dependent on increased arginase expression and/or activity. pulmonary vascular resistance; airway resistance; nitric oxide GIVEN THE HIGH FETAL PULMONARY vascular resistance, pulmonary blood flow prenatally is less than 10% of the total cardiac output. Pulmonary vascular resistance rapidly decreases at birth and reaches the low physiological level of adults at the end of the neonatal period (12). The factors accounting for maintenance of high pulmonary vascular resistance prenatally and its rapid decrease after birth are not completely understood. Pulmonary vascular nitric oxide (NO) availability and its relaxant effect on smooth muscle are considered to play an important role in the transition from fetal to neonatal circulation (1).NO is produced by nitric oxide synthases (NOS). In the lung, three NOS isoforms are present. Endothelial NOS (eNOS) is expressed in pulmonary vascular endothelium and bronchial epithelium, whereas neuronal (nNOS) and inducible (iNOS)

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Section: Discussionsupporting

confidence: 53%

Developmental changes in arginase expression and activity in the lung

Belik

Shehnaz²,

Pan³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Arginase II also plays a role in collagen synthesis as was shown in a murine model of bleomycin-induced fibrosis. 33 In addition, Que and colleagues 34 showed the induction of arginase I and II during the fibroproliferative phase of hyperoxic lung injury in rats. The increase in arginase II in our model when peribronchiolar fibrosis (40 days) is observed is consistent with its involvement in repair processes.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiles Reveal Increased mClca3 (Gob5) Expression and Mucin Production in a Murine Model of Asbestos-Induced Fibrogenesis

Sabo‐Attwood

Ramos-Niño

Bond

et al. 2005

The American Journal of Pathology

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To elucidate genes important in development or repair of asbestos-induced lung diseases, gene expression was examined in mice after inhalation of chrysotile asbestos for 3, 9, and 40 days. We identified changes in the expression of genes linked to proliferation (cyclin B2, CDC20, and CDC28 protein kinase regulatory subunit 2), inflammation (CCL9, CCL6, complement component 1, chitinase3-like 3, TNF superfamily member 10, and IL-1B), and matrix remodeling (MMP12, MMP3, integrin ␣X, and cathepsins K, Z, B, and S). The most highly induced gene at all time points was mclca3 (gob5), a putative calcium-activated chloride channel involved in the regulation of mucus production and/or secretion. Using histochemistry, we demonstrated accumulation of mucus and increased mClca3 protein in the bronchiolar epithelium of asbestos-exposed mice at all time points but peaking at 9 days. Cytokine levels (interleukin-1␤, interleukin-4, interleukin-6) in bronchoalveolar lavage fluid also increased at 9 days, suggesting Th2-mediated immunity may play a role in asbestosinduced mucus production. In contrast, levels of cathepsin K, a potent elastase, increased between 3 and 40 days at both the mRNA and protein levels, localizing primarily in CD45-positive leukocytes and interstitial cells. Identification of genes involved in lung injury and remodeling after asbestos exposure could aid in defining mechanisms of airborne particulate-

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“…The hyperoxic-mice of each strain were exposed continuously to >99% O 2 (flow rate of 10 L/min; CO 2 <0.1%; temp=25-26°C; and humidity<40%) in polystyrene chambers for 72 hours as described previously (Que et al 1998;Folz et al 1999), except for 10 min/day when the cages were opened to room air for general maintenance. The air-exposed control mice from each strain were housed in the same chambers and exposed to room air under identical flow, temperature, and humidity conditions for the same time period.…”

Section: Exposuresmentioning

confidence: 99%

Genetic basis of murine responses to hyperoxia-induced lung injury

et al. 2006

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To evaluate the effect of genetic background on oxygen (O 2 ) toxicity, nine genetically diverse mouse strains (129/SvIm, A/J, BALB/cJ, BTBR+(T)/tf/tf, CAST/Ei, C3H/HeJ, C57BL/6J, DBA/2J, and FVB/NJ) were exposed to >99% O 2 for 72 hours. Immediately following the hyperoxic challenge, the mouse strains demonstrated distinct pathophysiologic responses. The BALB/cJ and CAST/Ei strains, which were the only strains to demonstrate mortality from the hyperoxic challenges, were also the only strains to display significant neutrophil infiltration into their lower respiratory tract. In addition, the O 2 -challenged BALB/cJ and CAST/Ei mice were among six strains (A/J, BALB/cJ, CAST/Ei, BTBR+(T)/tf/tf, DBA/2J and C3H/HeJ) that had significantly increased IL-6 concentrations in the whole lung lavage fluid and were among all but one strain that had large increases in lung permeability compared to air-exposed controls. By contrast, the DBA/2J strain was the only strain not to have any significant alterations in lung permeability following hyperoxic challenge. The expression of the extracellular matrix (ECM) proteins, including collagens I, III and IV, fibronectin-I, and tenascin-C, also varied markedly among the mouse strains, as did the activities of total superoxide dismutase (SOD) and manganese-SOD (Mn-SOD or SOD2). These data suggest that the response to O 2 depends, in part, on the genetic background and that some of the strains analyzed could be used to identify specific loci and genes underlying the response to O 2 .

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Induction of arginase isoforms in the lung during hyperoxia

Cited by 82 publications

References 19 publications

Developmental changes in arginase expression and activity in the lung

Developmental changes in arginase expression and activity in the lung

Gene Expression Profiles Reveal Increased mClca3 (Gob5) Expression and Mucin Production in a Murine Model of Asbestos-Induced Fibrogenesis

Genetic basis of murine responses to hyperoxia-induced lung injury

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