CLAUDE PIANTADOSI

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..Recent evidence indicates that these cell defenses also include mitochondrial biogenesis and the clearance of damaged mitochondria through autophagy...

..A small number of SNO proteins, generated by various mechanisms, are characteristically found in mammalian mitochondria and influence the regulation of oxidative phosphorylation and other aspects of mitochondrial function...

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..Because inhaled particles, such as silica, and certain infections can cause secondary pulmonary alveolar proteinosis (PAP), we tested the hypothesis that idiopathic PAP is associated with an altered iron homeostasis in the human lung...

..This study discloses novel redox regulation of NRF-1 phosphorylation and nuclear translocation by phosphatidylinositol 3,4,5-triphosphate kinase/Akt signaling in controlling Tfam induction by an anti-oxidant pro-survival network...

..The implications are that cellular CO can activate or deactivate mitochondria for initiation of apoptosis in vivo...

..SNO-hemoglobin is the archetype for the role of S-nitrosylation in a newly identified class of biological signals, and disturbances in SNO-hemoglobin activity are associated with the pathogenesis of several important vascular diseases...

..This commentary presents a rationale for focusing American efforts in space on such a Moon base in order to promote understanding of the long-term physiological effects of living on a planetary body outside the Van Allen belts...

..The ability to noninvasively monitor the O(2) delivery-uptake relationship has made NIR spectroscopy a unique tool for the assessment of tissue oxygen sufficiency in health and disease...

..These findings disclose a novel role for NRF-1 in the transcriptional control of Complex II and prevention of pseudo-hypoxic gene expression in aerobic cardiac cells...

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..These findings disclose a highly structured transcriptional network that couples mitochondrial biogenesis to counter-inflammation with major implications for immune suppression in sepsis...

..Although gas-bubble formation may be aggravated by acoustic energy, more rigorous investigation is needed before sonar can be firmly linked to bubble formation in whales...

..This brief overview provides a conceptual framework for understanding CO biology in terms of this physiological-pathological hierarchy...

..These data indicate NO can influence pore transition by oxidation of thiols that produce conformational changes governing the ATP interaction at the adenine nucleotide transporter...

..This article provides a brief update on the biochemistry of CO as it relates to Hp binding, chemical oxidative processes, and cellular function...

..NRF-1 expression and growth were restored by exogenous oxidant exposure indicating that oxidative stress stimulates biogenesis in part via NRF-1 activation and corresponding to recovery events after LPS-induced liver damage...

..Thus, EC-SOD promotes NO* vasodilation by scavenging *O2- while hyperoxia opposes NO* and promotes constriction by enhancing endogenous *O2- generation and decreasing basal vasodilator effects of NO*...

..Chemical restoration of SNO-Hb levels in both animals and patients restores the vasodilator activity of RBCs, and this activity is associated with improved oxygenation and lower PAPs...

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..Our results also help elucidate the link between RBC dyscrasias and cardiovascular morbidity...

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..The findings disclose mitochondrial CO and H(2)O(2) as new activating factors in cardiac mitochondrial biogenesis...

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..We propose that extrapulmonary, neurogenic events predominate in the pathogenesis of acute pulmonary oxygen toxicity in hyperbaric oxygenation, as nNOS activity drives lung injury by modulating the output of central autonomic pathways...

..These findings demonstrate the decisive participation of NOS2 induction by TLR4 in optimization of mitochondrial biogenesis and MHC expression after gram-negative challenge...

..We thus disclose a novel ferri-reductase mechanism of NTBI uptake by human lung cells that employs superoxide exchange for HCO3- by AE2 protein in the plasma membrane...

..The extent, timing, and significance of mitochondrial injury and recovery in bacterial sepsis are poorly characterized, although oxidative and nitrosative mitochondrial damage have been implicated in the development of organ failure...

..These data provide the first link between LPS-mediated hepatic injury and a specific oxidative mtDNA deletion, which inhibits mitochondrial transcription and is restored by activation of mechanisms that lead to biogenesis...

..These findings demonstrate that hypoxic preconditioning elicits subcortical mitochondrial biogenesis by a novel mechanism that requires nNOS regulation of PGC-1alpha and CREB...

..In addition, we demonstrated that nitric oxide derived from nNOS is involved in a neurogenic mechanism of HBO2-induced lung injury that is linked to central nervous system oxygen toxicity through adrenergic/cholinergic pathways...

..CONCLUSIONS: These novel findings disclose a duality of reactive oxygen species (ROS) effect in the heart's response to LPS in which oxidative mitochondrial damage is opposed by oxidant stimulation of biogenesis...

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..These data disclose the dual role of TLR4 in mtDNA damage and compensatory mitochondrial biogenic responses after innate immune activation...

..These data provide the first direct evidence that EC-SOD is itself a target of nitration in hyperoxia, and offer a plausible explanation for low EC-SOD activity despite its increased secretion by O(2)-exposed neonatal lung...

..This study demonstrates that GSNO can regulate vascular tone in the intact lung by a reversible mechanism involving inhibition of the response to 5-HT...

..We conclude that iron-catalyzed production of oxalate from ascorbate can account for the deposition of this crystal on ferruginous bodies...

..Cycled ruthenium also exhibited a much greater increase in capacitance after cycling, consistent with the formation of a conductive surface layer...

..This finding indicates a unique and unexpected mechanism of metabolic adaptation to pulmonary fibrotic injuries...

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..These results indicate that O2-* produced by endothelial NOS in normoxia and unidentified sources in hypoxia regulate pulmonary vascular tone via AE2...

..Therefore, blockade of TF-FVIIa complex protects the lung from injury by LPS in part by reducing local expression of proinflammatory cytokines and may offer promise for therapy of acute lung injury...

..This study demonstrates that AE2 expression is regulated by oxidative stress in airway epithelial cells and that this regulation correlates with activation of AP-1...

..In addition, the formation of S-nitrosothiols in other proteins may regulate an array of physiological functions...

..Together, these data demonstrate that intracellular iron accumulation by airway epithelium requires concurrent Na(+)/K(+)exchange...

..To elucidate long-term outcomes in 65 consecutive patients meeting a uniform definition of mandibular osteoradionecrosis (ORN) treated with multimodality therapy including hyperbaric oxygen (HBO)...

..Moreover, the identification of mir-202-3p as a potential factor for Ppargc1a and Ppargc1b repression in acute inflammation may open new avenues for mitochondrial research and, potentially, therapy...

..Likewise, improved knowledge of NO-based mechanisms of pulmonary oxygen toxicity may enhance our understanding of other types of lung injury associated with oxidative or nitrosative stress...

..This mtDNA damage is associated with altered expression of mitochondrial cell death proteins, thereby suggesting a novel mechanism for systemic or environmental pro-oxidants to influence apoptosis...

..This study tested the hypothesis that enhancement of S-nitrosylated hemoglobin by ethyl nitrite inhalation improves outcome after experimental subarachnoid hemorrhage (SAH)...

..CO also increased lung HO activity and HO-1 mRNA and protein expression in small pulmonary arteries during hypoxia. These data indicate an overall propensity of CO in HH to promote vascular remodeling and increase PVR in vivo...

..These results show that blockade of coagulation attenuates acute lung and renal injury in established Gram-negative sepsis accompanied by antiinflammatory effects of therapy...

..007) but not after high dose HBO-PC. Thus, when temperature variability is eliminated, HBO-PC and HPC elicit similar preconditioning efficacy in neonatal brain but invoke different defenses against oxidative stress...

..production decreased when Dcytb function was blocked. The presence of Dcytb in airway epithelial cells and its regulation by iron therefore may contribute to pulmonary cytoprotection...

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..Blockade of factor X binding to the tissue factor-factor VIIa complex attenuates lung and organ injuries in established E. coli sepsis by attenuating the neutrophilic response and inflammatory pathways...

..The present review summarizes oxygen's capacity, acting through its reactive intermediates, to recruit the enzymatic antioxidant defenses, to stimulate cell repair processes, and to mitigate cellular damage...

..We conclude that epithelial permeability in the intact lung can be assessed using fluorescent solutes, and that increased permeation of hydrophilic solutes may enhance lung edema formation...

..Damage to mitochondrial DNA (mtDNA) by the production of reactive oxygen species during inflammatory states, such as sepsis, is repaired by poorly understood mechanisms...

..Thus PDE-5 blockers oppose the protective vasoconstriction that is the initial response to hyperbaric hyperoxia, decreasing the safety of HBO(2) by hastening onset of CNS O(2) toxicity...

..These findings support our hypothesis that HBO(2) increases PO(2) in brain in direct proportion to rCBF...

..Chlorpheniramine attenuated the effect, suggesting that the blood pressure response in rats is related to histamine release rather than the protection of nitric oxide...

..We elicit the NO release by decreasing the oxygen concentration in the gaseous atmosphere surrounding the drop...

..These pathways seem to be the primary mechanism for control of oxidative stress presented by iron in the respiratory tract...

..These findings imply that the therapeutic index of anthracycline cancer chemotherapeutics can be improved by the protection of cardiac mitochondrial biogenesis...

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..These results thus demonstrate for the first time a primary role for DMT1 in lung metal transport and detoxification...

..Increased expression of -IRE DMT1 in the lungs of the Hp mice could be responsible for elevated concentrations of the metal in these tissues...

..We conclude that airway epithelial cells increase mRNA and expression of the Nramp2/DMT1/DCT1 without an IRE after exposure to iron. The increase results in an elevated transport of iron and its probable detoxification by these cells...

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..Increased expression of this protein appears to be included in a coordinated response of the cell and tissue where the function might be to diminish availability of metal...

..These data demonstrate a novel cGMP-independent mechanism of reversible alpha1-adrenergic receptor inhibition by S-nitrosothiols...

..We conclude that the response of respiratory epithelial cells to asbestos includes oxidant-mediated mechanisms to sequester catalytically active iron associated with the fiber...

..These studies suggest the presence of iron mobilization and/or detoxification pathways in the lung that are crucial for iron homeostasis and lung defense...

..Furthermore, prenatal hypoxia delays secretion of active EC-SOD enzyme. These findings have important implications for the effects of prenatal asphyxia on postnatal response to oxidant stress...

..This loss of cellular iron after CO is in line with certain biological effects of the gas that have been implicated in the protection of cell viability...

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..A successfully optimized strategy could greatly attenuate persistence of pulmonary inflammation and facilitate the resolution of human ARDS. ..

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..A successful test of our hypothesis would establish a unifying mechanism for the diverse protective roles of HO-1 in health and disease. ..