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6. A-Kinase Anchor Protein 1 deficiency causes mitochondrial dysfunction in mouse model of hyperoxia induced acute lung injury

Author

Soundararajan, Ramani, Hernández-Cuervo, Helena, Stearns, Timothy M, Griswold, Anthony J, Patil, Sahebgowda Sidramagowda, Fukumoto, Jutaro, Narala, Venkata Ramireddy, Galam, Lakshmi, Lockey, Richard, and Kolliputi, Narasaiah

Subjects
Pharmacology, Pharmacology (medical)
Abstract

Background: Critically ill patients on supplemental oxygen therapy eventually develop acute lung injury (ALI). Reactive oxygen species (ROS) produced during ALI perturbs the mitochondrial dynamics resulting in cellular damage. Genetic deletion of the mitochondrial A-kinase anchoring protein 1 (Akap1) in mice resulted in mitochondrial damage, Endoplasmic reticulum (ER) stress, increased expression of mitophagy proteins and pro-inflammatory cytokines, exacerbating hyperoxia-induced Acute Lung Injury (HALI).Objective: Despite a strong causal link between mitochondrial dysfunction and HALI, the mechanisms governing the disease progression at the transcriptome level is unknown.Methods: In this study, RNA sequencing (RNA-seq) analysis was carried out using the lungs of Akap1 knockout (Akap1−/−) mice exposed to normoxia or 48 h of hyperoxia followed by quantitative real time PCR and Ingenuity pathway analysis (IPA). Western blot analysis assessed mitochondrial dysfunction, OXPHOS complex (I-V), apoptosis and antioxidant proteins. Mitochondrial enzymatic assays was used to measure the aconitase, fumarase, citrate synthase activities in isolated mitochondria from Akap1−/− vs. Wt mice exposed to hyperoxia.Results: Transcriptome analysis of Akap1−/− exposed to hyperoxia reveals increases in transcripts encoding electron transport chain (ETC) and tricarboxylic acid cycle (TCA) proteins. Ingenuity pathway analysis (IPA) shows enrichment of mitochondrial dysfunction and oxidative phosphorylation in Akap1−/− mice. Loss of AKAP1, coupled with oxidant injury, significantly decreases the activities of TCA enzymes. Mechanistically, a significant loss of dynamin-related protein 1 (Drp1) phosphorylation at the protein kinase A (PKA) site Serine 637 (Ser637), decreases in Akt phosphorylation at Serine 437 (Ser47) and increase in the expression of pro-apoptotic protein Bax indicate mitochondrial dysfunction. Heme oxygenase-1 (HO-1) levels significantly increased in CD68 positive alveolar macrophages in Akap1−/− lungs, suggesting a strong antioxidant response to hyperoxia.Conclusion: Overall these results suggest that AKAP1 overexpression and modulation of Drp1 phosphorylation at Ser637 is an important therapeutic strategy for acute lung injury.

Published
2022
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7. Aberrant Expression of ACO1 in Vasculatures Parallels Progression of Idiopathic Pulmonary Fibrosis

Author

Fukumoto, Jutaro, primary, Lin, Muling, additional, Banday, Mudassir Meraj, additional, Patil, Sahebgowda Sidramagowda, additional, Krishnamurthy, Sudarshan, additional, Breitzig, Mason, additional, Soundararajan, Ramani, additional, Galam, Lakshmi, additional, Narala, Venkata Ramireddy, additional, Johns, Colleen, additional, Patel, Kapilkumar, additional, Dunning, John, additional, Lockey, Richard F., additional, Sharma, Nirmal S., additional, and Kolliputi, Narasaiah, additional

Published
2022
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9. Mitochondrial Protein Akap1 Deletion Exacerbates Endoplasmic Reticulum Stress in Mice Exposed to Hyperoxia

Author

Sidramagowda Patil, Sahebgowda, primary, Soundararajan, Ramani, additional, Fukumoto, Jutaro, additional, Breitzig, Mason, additional, Hernández-Cuervo, Helena, additional, Alleyn, Matthew, additional, Lin, Muling, additional, Narala, Venkata Ramireddy, additional, Lockey, Richard, additional, Kolliputi, Narasaiah, additional, and Galam, Lakshmi, additional

Published
2022
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10. Lung fibrosis is induced in ADAR2 overexpressing mice via HuR‐induced CTGF signaling

Author

Soundararajan, Ramani, primary, Varanasi, Sai Manasa, additional, Patil, Sahebgowda Sidramagowda, additional, Srinivas, Sriraja, additional, Hernández‐Cuervo, Helena, additional, Czachor, Alexander, additional, Bulkhi, Adeeb, additional, Fukumoto, Jutaro, additional, Galam, Lakshmi, additional, Lockey, Richard F., additional, and Kolliputi, Narasaiah, additional

Published
2022
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13. Aberrant Expression of ACO1 in Vasculatures Parallels Progression of Idiopathic Pulmonary Fibrosis.

Author

Jutaro Fukumoto, Muling Lin, Banday, Mudassir Meraj, Patil, Sahebgowda Sidramagowda, Krishnamurthy, Sudarshan, Breitzig, Mason, Soundararajan, Ramani, Galam, Lakshmi, Narala, Venkata Ramireddy, Johns, Colleen, Patel, Kapil kumar, Dunning, John, Lockey, Richard F., Sharma, Nirmal S., and Kolliputi, Narasaiah

Abstract

Rationale: Idiopathic pulmonary fibrosis (IPF) is characterized by mitochondrial dysfunction. However, details about the non-mitochondrial enzymes that sustain the proliferative nature of IPF are unclear. Aconitases are a family of enzymes that sustain metabolism inside and outside mitochondria. It is hypothesized that aconitase 1 (ACO1) plays an important role in the pathogenesis of IPF given that ACO1 represents an important metabolic hub in the cytoplasm. Objectives: To determine if ACO1 expression in IPF lungs shows specific patterns that may be important in the pathogenesis of IPF. To determine the similarities and differences in ACO1 expression in IPF, bleomycin-treated, and aging lungs. Methods: ACO1 expression in IPF lungs were characterized and compared to non-IPF controls by western blotting, immunostaining, and enzymatic activity assay. ACO1-expressing cell types were identified by multicolor immunostaining. Using similar methods, the expression profiles of ACO1 in IPF lungs versus bleomycin-treated and aged mice were investigated. Measurements and main results: Lower lobes of IPF lungs, unlike non-IPF controls, exhibit significantly high levels of ACO1. Most of the signals colocalize with von Willebrand factor (vWF), a lineage marker for vascular endothelial cells. Bleomycin-treated lungs also show high ACO1 expressions. However, most of the signals colocalize with E-cadherin and/or prosurfactant protein C, representative epithelial cell markers, in remodeled areas. Conclusions: A characteristic ACO1 expression profile observed in IPF vasculatures may be a promising diagnostic target. It also may give clues as to how de novo angiogenesis contributes to the irreversible nature of IPF. [ABSTRACT FROM AUTHOR]

Published
2022
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14. Alda-1 Attenuates Hyperoxia-Induced Acute Lung Injury in Mice

Author

Sidramagowda Patil, Sahebgowda, primary, Hernández-Cuervo, Helena, additional, Fukumoto, Jutaro, additional, Krishnamurthy, Sudarshan, additional, Lin, Muling, additional, Alleyn, Matthew, additional, Breitzig, Mason, additional, Narala, Venkata Ramireddy, additional, Soundararajan, Ramani, additional, Lockey, Richard F., additional, Kolliputi, Narasaiah, additional, and Galam, Lakshmi, additional

Published
2021
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15. Mitochondrial Protein Akap 1 Deletion Exacerbates Endoplasmic Reticulum Stress in Mice Exposed to Hyperoxia.

Author

Sidramagowda Patil, Sahebgowda, Soundararajan, Ramani, Fukumoto, Jutaro, Breitzig, Mason, Hernández-Cuervo, Helena, Alleyn, Matthew, Lin, Muling, Narala, Venkata Ramireddy, Lockey, Richard, Kolliputi, Narasaiah, and Galam, Lakshmi

Subjects
MITOCHONDRIAL proteins, ENDOPLASMIC reticulum, ADULT respiratory distress syndrome, HYPEROXIA, CELL death, REACTIVE oxygen species, MICE
Abstract

Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome (ARDS), are treated with high concentrations of supplementary oxygen. However, prolonged exposure to high oxygen concentrations stimulates the production of reactive oxygen species (ROS), which damages the mitochondria and accumulates misfolded proteins in the endoplasmic reticulum (ER). The mitochondrial protein A-kinase anchoring protein 1 (Akap1) is critical for mitochondrial homeostasis. It is known that Akap1 deficiency results in heart damage, neuronal development impairment, and mitochondrial malfunction in preclinical studies. Our laboratory recently revealed that deleting Akap1 increases the severity of hyperoxia-induced ALI in mice. To assess the role of Akap1 deletion in ER stress in lung injury, wild-type and Akap1 −/− mice were exposed to hyperoxia for 48 h. This study indicates that Akap1 −/− mice exposed to hyperoxia undergo ER stress, which is associated with an increased expression of BiP, JNK phosphorylation, eIF2α phosphorylation, ER stress-induced cell death, and autophagy. This work demonstrates that deleting Akap1 results in increased ER stress in the lungs of mice and that hyperoxia exacerbates ER stress-related consequences. [ABSTRACT FROM AUTHOR]

Published
2022
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16. AKAP1 genetic deletion during hyperoxia causes mitochondrial damage

Author

Patil, Sahebgowda, primary, Alleyn, Matthew, additional, Fukumoto, Jutaro, additional, Lin, Muling, additional, Hernandez-Cuervo, Helena, additional, Soundararajan, Ramani, additional, Ramireddy, Venkat Narala, additional, Lockey, Richard, additional, Kolliputi, Narasaiah, additional, and Galam, Lakshmi, additional

Published
2020
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17. Lung Fibrosis is induced in Adarb1 transgenic mice via HuR induced CTGF signaling

Author

Soundararajan, Ramani, primary, Varanasi, Sai Manasa, additional, Patil, Sahebgowda, additional, Hernandez-Cuervo, Helena, additional, Czachor, Alexander, additional, Bulkhi, Adeeb, additional, Srinivas, Sriraja, additional, Fukumoto, Jutaro, additional, Alleyn, Matthew, additional, Galam, Lakshmi, additional, Lockey, Richard, additional, and Kolliputi, Narasaiah, additional

Published
2020
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18. Alda-1 attenuates hyperoxia-induced mitochondrial dysfunction in lung vascular endothelial cells

Author

Patil, Sahebgowda Sidramagowda, primary, Hernández-Cuervo, Helena, additional, Fukumoto, Jutaro, additional, Narala, Venkata Ramireddy, additional, Saji, Smita, additional, Borra, Monica, additional, Alleyn, Matthew, additional, Lin, Muling, additional, Soundararajan, Ramani, additional, Lockey, Richard, additional, Kolliputi, Narasaiah, additional, and Galam, Lakshmi, additional

Published
2019
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20. Altered expression of p63 isoforms and expansion of p63- and club cell secretory protein-positive epithelial cells in the lung as novel features of aging

Author

Fukumoto, Jutaro, primary, Sidramagowda Patil, Sahebgowda, additional, Krishnamurthy, Sudarshan, additional, Saji, Smita, additional, John, Irene, additional, Narala, Venkata Ramireddy, additional, Hernández-Cuervo, Helena, additional, Alleyn, Matthew, additional, Breitzig, Mason T., additional, Galam, Lakshmi, additional, Soundararajan, Ramani, additional, Chaudhari, Uddhav K., additional, Hansen, Barbara C., additional, Lockey, Richard F., additional, and Kolliputi, Narasaiah, additional

Published
2019
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21. The Role of Adenosine Deaminase Acting on RNA (ADAR) Family of Proteins in Hyperoxia Induced Acute Lung Injury

Author

Soundararajan, Ramani, primary, Varanasi, Manasa, additional, Czachor, Alexander, additional, Srinivas, Sriraja, additional, Patil, Sahebgowda, additional, Bulki, Adeeb, additional, Hernandez‐Cuervo, Helena, additional, Fukumoto, Jutaro, additional, Alleyn, Matthew, additional, Galam, Lakshmi, additional, Lockey, Richard F, additional, and Kolliputi, Narasaiah, additional

Published
2019
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22. Alda-1 Attenuates Hyperoxia-Induced Acute Lung Injury in Mice

Author

Patil, Sahebgowda, primary, Hernandez-Cuervo, Helena, additional, Fukumoto, Jutaro, additional, Saji, Smita, additional, Alleyn, Matthew, additional, Soundararajan, Ramani, additional, Lockey, Richard F., additional, Kolliputi, Narasaiah, additional, and Galam, Lakshmi, additional

Published
2019
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24. Oxidative stress induces club cell proliferation and pulmonary fibrosis in Atp8b1 mutant mice

Author

Fukumoto, Jutaro, primary, Leung, Joseph, additional, Cox, Ruan, additional, Czachor, Alexander, additional, Parthasarathy, Prasanna Tamarapu, additional, Lagishetty, Venu, additional, Mandry, Maria, additional, Hosseinian, Nima, additional, Patel, Priyanshi, additional, Perry, Brittany, additional, Breitzig, Mason T., additional, Alleyn, Matthew, additional, Failla, Athena, additional, Cho, Young, additional, Cooke, Andrew J., additional, Galam, Lakshmi, additional, Soundararajan, Ramani, additional, Sharma, Nirmal, additional, Lockey, Richard F., additional, and Kolliputi, Narasaiah, additional

Published
2019
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28. The role of club cell phenoconversion and migration in idiopathic pulmonary fibrosis

Author

Fukumoto, Jutaro, primary, Soundararajan, Ramani, additional, Leung, Joseph, additional, Cox, Ruan, additional, Mahendrasah, Sanjay, additional, Muthavarapu, Neha, additional, Herrin, Travis, additional, Czachor, Alexander, additional, Tan, Lee C., additional, Hosseinian, Nima, additional, Patel, Priyanshi, additional, Gone, Jayanthraj, additional, Breitzig, Mason T., additional, Cho, Young, additional, Cooke, Andrew J., additional, Galam, Lakshmi, additional, Narala, Venkata Ramireddy, additional, Pathak, Yashwant, additional, Lockey, Richard F., additional, and Kolliputi, Narasaiah, additional

Published
2016
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30. Akap1 genetic deletion increases the severity of hyperoxia-induced acute lung injury in mice.

Author

Narala, Venkata Ramireddy, Fukumoto, Jutaro, Hernández-Cuervo, Helena, Patil, Sahebgowda Sidramagowda, Krishnamurthy, Sudarshan, Breitzig, Mason, Galam, Lakshmi, Soundararajan, Ramani, Lockey, Richard F., and Kolliputi, Narasaiah

Abstract

Critically ill patients are commonly treated with high levels of oxygen, hyperoxia, for prolonged periods of time. Unfortunately, extended exposure to hyperoxia can exacerbate respiratory failure and lead to a high mortality rate. Mitochondrial A-kinase anchoring protein (Akap) has been shown to regulate mitochondrial function. It has been reported that, under hypoxic conditions, Akap121 undergoes proteolytic degradation and promotes cardiac injury. However, the role of Akap1 in hyperoxia-induced acute lung injury (ALI) is largely unknown. To address this gap in our understanding of Akap1, we exposed wild-type (wt) and Akap1−/− mice to 100% oxygen for 48 h, a time point associated with lung damage in the murine model of ALI. We found that under hyperoxia, Akap1−/− mice display increased levels of proinflammatory cytokines, immune cell infiltration, and protein leakage in lungs, as well as increased alveolar capillary permeability compared with wt controls. Further analysis revealed that Akap1 deletion enhances lung NF-κB p65 activity as assessed by immunoblotting and DNA-binding assay and mitochondrial autophagy-related markers, PINK1 and Parkin. Ultrastructural analysis using electron microscopy revealed that Akap1 deletion was associated with remarkably aberrant mitochondria and lamellar bodies in type II alveolar epithelial cells. Taken together, these results demonstrate that Akap1 genetic deletion increases the severity of hyperoxia-induced acute lung injury in mice. [ABSTRACT FROM AUTHOR]

Published
2018
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37. Dysregulation of CLOCK gene expression in hyperoxia-induced lung injury

Author

Lagishetty, Venu, primary, Parthasarathy, Prasanna Tamarapu, additional, Phillips, Oluwakemi, additional, Fukumoto, Jutaro, additional, Cho, Young, additional, Fukumoto, Itsuko, additional, Bao, Huynh, additional, Cox, Ruan, additional, Galam, Lakshmi, additional, Lockey, Richard F., additional, and Kolliputi, Narasaiah, additional

Published
2014
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44. Derrubone, an Inhibitor of the Hsp90 Protein Folding Machinery

Author

Kyle Hadden, M., S. J. Blagg, Brian, Galam, Lakshmi, L. Matts, Robert, and E. Gestwicki, Jason

Abstract

High-throughput screening of a library of diverse molecules has identified derrubone ( 1), an isoflavone natural product from Derris robusta, as a potent Hsp90 inhibitor. Subsequent testing in several cellular-based assays established 1as a low micromolar inhibitor in vitro. In addition, derrubone induced the degradation of numerous Hsp90 client proteins, a hallmark effect resulting from Hsp90 inhibition. The identification of 1as an Hsp90 inhibitor provides a new natural product scaffold upon which the development of novel Hsp90 inhibitors can be pursued.

Published
2007
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45. Abstract 14846: BMI1 Plays a Critical Role in Hyperoxia-Induced Acute Lung Injury

Author

Hernandez-Cuervo, Helena, Soundararajan, Ramani, Patil, Sahebgowda, Alleyn, Matthew, Breitzig, Mason, Narala, Venkata, Galam, Lakshmi, Lockey, Richard, and Kolliputi, Narasaiah

Abstract

Acute Lung Injury (ALI), also known as mild Acute Respiratory Distress Syndrome (ARDS), is a disease that leads to acute hypoxemic respiratory failure with bilateral pulmonary infiltrates and a decrease in the availability of gas exchange. ALI is caused by an innate immune response, resulting in the migration of white blood cells and cytokines release, followed by alterations in mitochondrial function, increased reactive oxygen species production, and oxidative stress. Several studies have shown that mitochondrial alterations are key events in the mechanism of ALI development and could be possible targets in the treatment of the disease. While ALI/ARDS inherently causes deleterious damage in the lungs, it also has system-wide repercussions in several other target organs, evidenced by hemodynamic imbalances, pulmonary vascular dysfunction, pulmonary hypertension, cor pulmonale, and cardiac hypertrophy. Research determined that BMI1 plays a role in mitochondrial function, this role remains functionally unknown, and the metabolic pathway through which BMI1 regulates mitochondrial function and oxidative stress has not been established. This will be the first study to elucidate the mechanistic role of BMI1 in Hyperoxia induced Acute Lung Injury (HALI). We cultured lung epithelial cells (H441 cell line) and knocked down BMI1 expression invitroand exposed them to 48h of hyperoxia, followed by protein isolation, staining, and functional assays. For the invivomodel, we generated whole body BMI1 knockout (KO) mice and exposed them and their wild type littermates to normoxia and hyperoxia. Lungs were collected for mitochondrial function and protein analysis. Our results indicate that BMI1 expression is involved in the regulation of mitochondrial biogenesis markers and influences the expression of several proteins in the PI3K/AKT pathway in H441 cells. WT mice after hyperoxia displayed decreased BMI1 expression and increased mitochondrial fission. Our findings indicate that BMI1 plays a pivotal role in mitochondrial function during HALI invitroand invivo. These results make BMI1 a compelling future target of treatment to improve the conditions of ALI/ARDS patients and reduce the comorbidities associated with cardiac hypertrophy and cor pulmonale.

Published
2019
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47. A High-Throughput Screen for Inhibitors of the Hsp90-Chaperone Machine.

Author

Davenport J, Galam L, and Matts RL

Subjects
Animals, Heat-Shock Response, Humans, Luciferases, HSP90 Heat-Shock Proteins antagonists & inhibitors, High-Throughput Screening Assays methods, Proteomics methods
Abstract

Hsp90 has emerged as a key chemotherapeutic target for the development of drugs for the treatment of cancer and neurodegenerative diseases. The shortcomings of many of the Hsp90 inhibitors that have made it to clinical trials have bolstered the need to identify new lead compounds with superior properties. Here, we describe a high-throughput screen for the identification of Hsp90 inhibitors based on the refolding of thermally denatured firefly luciferase.

Published
2018
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48. Deletion of P2X7 attenuates hyperoxia-induced acute lung injury via inflammasome suppression.

Author

Galam L, Rajan A, Failla A, Soundararajan R, Lockey RF, and Kolliputi N

Subjects
Acute Lung Injury etiology, Acute Lung Injury immunology, Alveolar Epithelial Cells metabolism, Animals, Caspase 1 metabolism, Cells, Cultured, Coculture Techniques, Female, Hyperoxia genetics, Hyperoxia immunology, Interleukin-1beta biosynthesis, Lipid Peroxidation, Male, Membrane Potentials, Mice, Inbred C57BL, Mice, Knockout, Neutrophil Infiltration, Protective Factors, Receptors, Purinergic P2X7 metabolism, Acute Lung Injury genetics, Hyperoxia complications, Inflammasomes metabolism, Receptors, Purinergic P2X7 genetics
Abstract

Increasing evidence shows that hyperoxia is a serious complication of oxygen therapy in acutely ill patients that causes excessive production of free radicals leading to hyperoxia-induced acute lung injury (HALI). Our previous studies have shown that P2X7 receptor activation is required for inflammasome activation during HALI. However, the role of P2X7 in HALI is unclear. The main aim of this study was to determine the effect of P2X7 receptor gene deletion on HALI. Wild-type (WT) and P2X7 knockout (P2X7 KO) mice were exposed to 100% O2 for 72 h. P2X7 KO mice treated with hyperoxia had enhanced survival in 100% O2 compared with the WT mice. Hyperoxia-induced recruitment of inflammatory cells and elevation of IL-1β, TNF-α, monocyte chemoattractant protein-1, and IL-6 levels were attenuated in P2X7 KO mice. P2X7 deletion decreased lung edema and alveolar protein content, which are associated with enhanced alveolar fluid clearance. In addition, activation of the inflammasome was suppressed in P2X7-deficient alveolar macrophages and was associated with suppression of IL-1β release. Furthermore, P2X7-deficient alveolar macrophage in type II alveolar epithelial cells (AECs) coculture model abolished protein permeability across mouse type II AEC monolayers. Deletion of P2X7 does not lead to a decrease in epithelial sodium channel expression in cocultures of alveolar macrophages and type II AECs. Taken together, these findings show that deletion of P2X7 is a protective factor and therapeutic target for the amelioration of hyperoxia-induced lung injury., (Copyright © 2016 the American Physiological Society.)

Published
2016
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49. Dysregulation of CLOCK gene expression in hyperoxia-induced lung injury.

Author

Lagishetty V, Parthasarathy PT, Phillips O, Fukumoto J, Cho Y, Fukumoto I, Bao H, Cox R Jr, Galam L, Lockey RF, and Kolliputi N

Subjects
Animals, CLOCK Proteins genetics, Hyperoxia genetics, Hyperoxia pathology, Lung Injury genetics, Lung Injury pathology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, RNA, Messenger biosynthesis, RNA, Messenger genetics, CLOCK Proteins biosynthesis, Gene Expression Regulation, Hyperoxia metabolism, Lung Injury metabolism
Abstract

Hyperoxic acute lung injury (HALI) is characterized by inflammation and epithelial cell death. CLOCK genes are master regulators of circadian rhythm also implicated in inflammation and lung diseases. However, the relationship of CLOCK genes in hyperoxia-induced lung injury has not been studied. This study will determine if HALI alters CLOCK gene expression. To test this, wild-type and NALP3(-/-) mice were exposed to room air or hyperoxia for 24, 48, or 72 h. In addition, mice were exposed to different concentrations of hyperoxia (50, 75, or 100% O2) or room air for 72 h. The mRNA and protein levels of lung CLOCK genes, based on quantitative PCR and Western blot analysis, respectively, and their target genes are significantly elevated in mice exposed to hyperoxia compared with controls. Alterations in CLOCK genes are associated with increased inflammatory markers in bronchoalveolar lavage fluid of hyperoxic mice compared with controls. Histological examination of mice lungs exposed to hyperoxia show increased inflammation and alveolar congestion compared with controls. Our results indicate sequential increase in CLOCK gene expression in lungs of mice exposed to hyperoxia compared with controls. Additionally, data suggest a dose-dependent increase in CLOCK gene expression with increased oxygen concentrations. To validate if the expression changes related to CLOCK genes are indeed associated with inflammation, NALP3(-/-) was introduced to analyze loss of function in inflammation. Western blot analysis showed significant CLOCK gene downregulation in NALP3(-/-) mice compared with wild-type controls. Together, our results demonstrate that hyperoxia-mediated lung inflammation is associated with alterations in CLOCK gene expression., (Copyright © 2014 the American Physiological Society.)

Published
2014
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