Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Macrophages exposed to hyperoxia in the lung continue to survive for prolonged periods. We previously reported (Nyunoya, T., Powers, L. S., Yarovinsky, T. O., Butler, N. S., Monick, M. M., and Hunninghake, G. W. (2003) J. Biol. Chem. 278, 36099-36106) that hyperoxia induces cell cycle arrest and sustained extracellular signal-related kinase (ERK) activity in macrophages. In this study, we determined the mechanisms of hyperoxia-induced ERK activation and how ERK activity plays a pro-survival role in hyperoxia-exposed cells. Inhibition of ERK activity decreased survival of hyperoxia-exposed macrophages. This was due, at least in part, to down-regulation of the pro-apoptotic Bcl-2 family member, BimEL. In determining the mechanism of ERK activation by hyperoxia, we found that ERK activation was not associated with hyperoxia-induced activation of the upstream ERK kinase mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2. When we examined the ability of whole cell lysates from hyperoxia-exposed cells to dephosphorylate purified phosphorylated ERK, we found decreased ERK-directed phosphatase activity. Two particular ERK-directed phosphatases (protein phosphatase 2A and MAPK phosphatase-3) demonstrated decreased activity in hyperoxia-exposed cells. Moreover, whole cell lysates from normoxia-exposed cells depleted of PP2A or MAPK phosphatase-3 were also less able to dephosphorylate ERK. These data demonstrate that, in hyperoxia-exposed macrophages, sustained activation of ERK due to phosphatase down-regulation permits macrophage survival via effects on the balance between pro- and anti-apoptotic Bcl-2 family proteins.
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PMID:Macrophages survive hyperoxia via prolonged ERK activation due to phosphatase down-regulation. 1590 35

Maintenance of patency in distal airways is essential for gas exchange in neonatal life, and its disruption may have long-lasting effects on respiratory function. However, neural mechanisms that regulate caliber of intrapulmonary airways during early postnatal life, and their disruption by hyperoxic exposure, have not been well characterized. We have previously shown that cholinergically mediated airway contractile responses in rat pups are upregulated after hyperoxic exposure, and that increased expression of neuropeptides, such as substance P, may be contributory. More recently, we have documented impairment of neurally mediated airway relaxation in response to hyperoxic stress associated with loss of nitric oxide and prostaglandin-induced airway relaxation as well as inhibition of long chain myosin phosphatase. Our most recent data demonstrate significantly enhanced expression of the neurotrophin, brain-derived neurotrophic factor (BDNF) and its high affinity specific tyrosine kinase B (TrkB) receptor in hyperoxia-exposed airway smooth muscle. The existence of a BDNF-TrkB receptor autocrine and paracrine loops in the airways provides a basis for understanding local regulatory mechanisms of airway homeostasis. A mechanistic role for BDNF-TrkB signaling in hyperoxia-induced airway hyperreactivity in early postnatal life could serve to modulate both afferent and efferent neural pathways that result in enhanced contractile responses of immature airways exposed to hyperoxic stress. Greater insight into these neural pathways may lead to future preventive strategies for preterm infants surviving neonatal intensive care and developing chronic lung disease.
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PMID:Neonatal lung and airway injury: a role for neurotrophins. 1681 75

Exposure of rat pups to 100% oxygen is a model for studying neonatal lung injury. Airway reactivity is increased in this model, in part due to impaired airway smooth muscle (ASM) relaxation. We compared biochemical determinants of ASM contractility in rat pups exposed to 100% oxygen for 7 days vs. littermates raised in room air. The baseline quantities of ASM contractile proteins, extent of phosphorylation of the 20-kDa myosin regulatory light chain (LC(20)), and amount of the myosin-binding subunit of smooth muscle myosin phosphatase (MYPT) were all comparable between the two groups. Bethanechol-induced contraction increased the extent of phosphorylation of both LC(20) and MYPT in the hyperoxic group (45% and 70% over control, respectively). Relaxation after electrical field stimulation demonstrated greater phosphorylation of both LC(20) and MYPT in the hyperoxic group compared with controls (67% and 84%, respectively). To determine if hyperoxia induced changes in the isoforms of MYPT, isoform expression was also compared but differences were not found. To determine potential mechanisms whereby MYPT phosphorylation was increased by hyperoxia, separate tracheas were treated with the Rho kinase inhibitor Y-27632. This treatment completely eliminated differences in MYPT phosphorylation between the groups. Because phosphorylation of MYPT impairs the phosphatase activity of myosin phosphatase, these data suggest that hyperoxic conditioning during early postnatal life impairs relaxation through prolonging LC(20) phosphorylation. This mechanism might contribute to increased ASM reactivity seen in bronchopulmonary dysplasia.
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PMID:Hyperoxic conditions inhibit airway smooth muscle myosin phosphatase in rat pups. 1721 35