scholarly journals Hydrogen Sulfide—Clues from Evolution and Implication for Neonatal Respiratory Diseases

Children ◽  
2021 ◽  
Vol 8 (3) ◽  
pp. 213
Author(s):  
Abhrajit Ganguly ◽  
Gaston Ofman ◽  
Peter F Vitiello
Keyword(s):  
Hydrogen Sulfide ◽  
Lung Disease ◽  
Respiratory Diseases ◽  
Redox Homeostasis ◽  
Life Forms ◽  
Experimental Models ◽  
Animal Data ◽  
Neonatal Lung ◽  
Neonatal Chronic Lung Disease

Reactive oxygen species (ROS) have been the focus of redox research in the realm of oxidative neonatal respiratory diseases such as bronchopulmonary dysplasia (BPD). Over the years, nitric oxide (NO) and carbon monoxide (CO) have been identified as important gaseous signaling molecules involved in modulating the redox homeostasis in the developing lung. While animal data targeting aspects of these redox pathways have been promising in treating and/or preventing experimental models of neonatal lung disease, none are particularly effective in human neonatal clinical trials. In recent years, hydrogen sulfide (H2S) has emerged as a novel gasotransmitter involved in a magnitude of cellular signaling pathways and functions. The importance of H2S signaling may lie in the fact that early life-forms evolved in a nearly anoxic, sulfur-rich environment and were dependent on H2S for energy. Recent studies have demonstrated an important role of H2S and its synthesizing enzymes in lung development, which normally takes place in a relatively hypoxic intrauterine environment. In this review, we look at clues from evolution and explore the important role that the H2S signaling pathway may play in oxidative neonatal respiratory diseases and discuss future opportunities to explore this phenomenon in the context of neonatal chronic lung disease.

The role of matrix metalloproteinases -9 and -2 in development of neonatal chronic lung disease

2004 ◽  
Vol 93 (6) ◽  
pp. 791-796 ◽  
Author(s):  
DG Sweet ◽  
AE Curley ◽  
E Chesshyre ◽  
J Pizzotti ◽  
MS Wilbourn ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Lung Disease ◽  
Chronic Lung Disease ◽  
Matrix Metalloproteinases 9 ◽  
Neonatal Chronic Lung Disease

scholarly journals Role of unfolded proteins in lung disease

Thorax ◽  
2020 ◽  
Vol 76 (1) ◽  
pp. 92-99
Author(s):  
Kirsty L Bradley ◽  
Clare A Stokes ◽  
Stefan J Marciniak ◽  
Lisa C Parker ◽  
Alison M Condliffe
Keyword(s):  
Protein Synthesis ◽  
Er Stress ◽  
Respiratory Diseases ◽  
Viral Infections ◽  
Genetic Manipulation ◽  
Experimental Models ◽  
Misfolded Proteins ◽  
Pharmacological Agents ◽  
The Impact

The lungs are exposed to a range of environmental toxins (including cigarette smoke, air pollution, asbestos) and pathogens (bacterial, viral and fungal), and most respiratory diseases are associated with local or systemic hypoxia. All of these adverse factors can trigger endoplasmic reticulum (ER) stress. The ER is a key intracellular site for synthesis of secretory and membrane proteins, regulating their folding, assembly into complexes, transport and degradation. Accumulation of misfolded proteins within the lumen results in ER stress, which activates the unfolded protein response (UPR). Effectors of the UPR temporarily reduce protein synthesis, while enhancing degradation of misfolded proteins and increasing the folding capacity of the ER. If successful, homeostasis is restored and protein synthesis resumes, but if ER stress persists, cell death pathways are activated. ER stress and the resulting UPR occur in a range of pulmonary insults and the outcome plays an important role in many respiratory diseases. The UPR is triggered in the airway of patients with several respiratory diseases and in corresponding experimental models. ER stress has been implicated in the initiation and progression of pulmonary fibrosis, and evidence is accumulating suggesting that ER stress occurs in obstructive lung diseases (particularly in asthma), in pulmonary infections (some viral infections and in the setting of the cystic fibrosis airway) and in lung cancer. While a number of small molecule inhibitors have been used to interrogate the role of the UPR in disease models, many of these tools have complex and off-target effects, hence additional evidence (eg, from genetic manipulation) may be required to support conclusions based on the impact of such pharmacological agents. Aberrant activation of the UPR may be linked to disease pathogenesis and progression, but at present, our understanding of the context-specific and disease-specific mechanisms linking these processes is incomplete. Despite this, the ability of the UPR to defend against ER stress and influence a range of respiratory diseases is becoming increasingly evident, and the UPR is therefore attracting attention as a prospective target for therapeutic intervention strategies.

scholarly journals The complicated role of mitochondria in the podocyte

2020 ◽  
Vol 319 (6) ◽  
pp. F955-F965
Author(s):  
Nehaben A. Gujarati ◽  
Jessica M. Vasquez ◽  
Daniel F. Bogenhagen ◽  
Sandeep K. Mallipattu
Keyword(s):  
Kidney Disease ◽  
Oxidative Phosphorylation ◽  
Diabetic Kidney Disease ◽  
Kidney Diseases ◽  
Redox Homeostasis ◽  
Experimental Models ◽  
Glomerular Diseases ◽  
Podocyte Injury ◽  
Atp Generation

Mitochondria play a complex role in maintaining cellular function including ATP generation, generation of biosynthetic precursors for macromolecules, maintenance of redox homeostasis, and metabolic waste management. Although the contribution of mitochondrial function in various kidney diseases has been studied, there are still avenues that need to be explored under healthy and diseased conditions. Mitochondrial damage and dysfunction have been implicated in experimental models of podocytopathy as well as in humans with glomerular diseases resulting from podocyte dysfunction. Specifically, in the podocyte, metabolism is largely driven by oxidative phosphorylation or glycolysis depending on the metabolic needs. These metabolic needs may change drastically in the presence of podocyte injury in glomerular diseases such as diabetic kidney disease or focal segmental glomerulosclerosis. Here, we review the role of mitochondria in the podocyte and the factors regulating its function at baseline and in a variety of podocytopathies to identify potential targets for therapy.

scholarly journals The Role of Hydrogen Sulfide in Respiratory Diseases

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 682
Author(s):  
Saadullah Khattak ◽  
Qian-Qian Zhang ◽  
Muhammad Sarfraz ◽  
Pir Muhammad ◽  
Ebenezeri Erasto Ngowi ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Respiratory Diseases ◽  
Therapeutic Potential ◽  
Pulmonary Inflammation ◽  
Cellular Functions ◽  
Comprehensive Overview ◽  
Therapeutic Role ◽  
Diverse Range ◽  
Incidence And Mortality

Respiratory diseases are leading causes of death and disability around the globe, with a diverse range of health problems. Treatment of respiratory diseases and infections has been verified to be thought-provoking because of the increasing incidence and mortality rate. Hydrogen sulfide (H2S) is one of the recognized gaseous transmitters involved in an extensive range of cellular functions, and physiological and pathological processes in a variety of diseases, including respiratory diseases. Recently, the therapeutic potential of H2S for respiratory diseases has been widely investigated. H2S plays a vital therapeutic role in obstructive respiratory disease, pulmonary fibrosis, emphysema, pancreatic inflammatory/respiratory lung injury, pulmonary inflammation, bronchial asthma and bronchiectasis. Although the therapeutic role of H2S has been extensively studied in various respiratory diseases, a concrete literature review will have an extraordinary impact on future therapeutics. This review provides a comprehensive overview of the effective role of H2S in respiratory diseases. Besides, we also summarized H2S production in the lung and its metabolism processes in respiratory diseases.

scholarly journals α-Synuclein pathology in Parkinson disease activates homeostatic NRF2 anti-oxidant response

2021 ◽  
Author(s):  
Alberto Delaidelli ◽  
Mette Richner ◽  
Lixiang Jiang ◽  
Amelia van der Laan ◽  
Ida Bergholdt Jul Christiansen ◽  
...  
Keyword(s):  
Nervous System ◽  
Parkinson Disease ◽  
Redox Homeostasis ◽  
Alpha Synuclein ◽  
Experimental Models ◽  
Motor Nucleus ◽  
Related Factor ◽  
Dorsal Motor Nucleus ◽  
Anti Oxidant

Circumstantial evidence points to a pathological role of alpha-synuclein (aSyn; gene symbol SNCA), conferred by aSyn misfolding and aggregation, in Parkinson disease (PD) and related synucleionpathies. Several findings in experimental models implicate perturbations in the tissue homeostatic mechanisms triggered by pathological aSyn accumulation, including impaired redox homeostasis, as significant contributors in the pathogenesis of PD. The nuclear factor erythroid 2-related factor (NRF2) is recognized as the master regulator of cellular anti-oxidant response, both under physiological as well as in pathological conditions. Using immunohistochemical analyses, we show a robust nuclear NRF2 accumulation in post-mortem PD midbrain, detected by NRF2 phosphorylation on serine residue 40 (nuclear active p-NRF2, S40). Curated gene expression analyses of four independent publicly available microarray datasets revealed considerable alterations in NRF2-responsive genes in the disease affected regions in PD, including substantia nigra, dorsal motor nucleus of vagus, locus coeruleus and globus pallidus. To further examine the putative role of pathological aSyn accumulation on nuclear NRF2 response, we employed a transgenic mouse model of synucleionopathy (M83 line, Prnp-SNCA*Ala53Thr), which manifest widespread aSyn pathology (phosphorylated aSyn; S129) in the nervous system following intramuscular inoculation of exogenous fibrillar aSyn. We observed strong immunodetection of nuclear NRF2 in neuronal populations harboring p-aSyn (S129), and found an aberrant anti-oxidant and inflammatory gene response in the affected neuraxis. Taken together, our data support the notion that pathological aSyn accumulation impairs the redox homeostasis in nervous system, and boosting neuronal anti-oxidant response is potentially a promising approach to mitigate neurodegeneration in PD and related diseases.

scholarly journals Hydrogen Sulfide and Cellular Redox Homeostasis

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Zhi-Zhong Xie ◽  
Yang Liu ◽  
Jin-Song Bian
Keyword(s):  
Hydrogen Sulfide ◽  
Antioxidant Defense ◽  
Redox Homeostasis ◽  
Antioxidant Defense System ◽  
Ros Generation ◽  
Cellular Redox ◽  
Wide Range ◽  
Underlying Mechanisms ◽  
Antioxidant Effects

Intracellular redox imbalance is mainly caused by overproduction of reactive oxygen species (ROS) or weakness of the natural antioxidant defense system. It is involved in the pathophysiology of a wide array of human diseases. Hydrogen sulfide (H2S) is now recognized as the third “gasotransmitters” and proved to exert a wide range of physiological and cytoprotective functions in the biological systems. Among these functions, the role of H2S in oxidative stress has been one of the main focuses over years. However, the underlying mechanisms for the antioxidant effect of H2S are still poorly comprehended. This review presents an overview of the current understanding of H2S specially focusing on the new understanding and mechanisms of the antioxidant effects of H2S based on recent reports. Both inhibition of ROS generation and stimulation of antioxidants are discussed. H2S-induced S-sulfhydration of key proteins (e.g., p66Shc and Keap1) is also one of the focuses of this review.

scholarly journals 319 THE ROLE OF IL-8 IN PULMONARY INFLAMMATION DURING NEONATAL CHRONIC LUNG DISEASE

1994 ◽  
Vol 36 (1) ◽  
pp. 56A-56A ◽  
Author(s):  
S A Little ◽  
S Devin ◽  
T Dean ◽  
M Hall ◽  
M Ashton ◽  
...  
Keyword(s):  
Lung Disease ◽  
Chronic Lung Disease ◽  
Pulmonary Inflammation ◽  
Neonatal Chronic Lung Disease

scholarly journals Role of Hydrogen Sulfide in NRF2- and Sirtuin-Dependent Maintenance of Cellular Redox Balance

Antioxidants ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 129 ◽  
Author(s):  
Tiziana Corsello ◽  
Narayana Komaravelli ◽  
Antonella Casola
Keyword(s):  
Hydrogen Sulfide ◽  
Redox Homeostasis ◽  
Antioxidant Properties ◽  
Redox Balance ◽  
Cellular Redox ◽  
Endogenous Production ◽  
Organ Specific ◽  
Mercaptopyruvate Sulfurtransferase ◽  
Antioxidant Effects

Hydrogen sulfide (H2S) has arisen as a critical gasotransmitter signaling molecule modulating cellular biological events related to health and diseases in heart, brain, liver, vascular systems and immune response. Three enzymes mediate the endogenous production of H2S: cystathione β-synthase (CBS), cystathione γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST). CBS and CSE localizations are organ-specific. 3-MST is a mitochondrial and cytosolic enzyme. The generation of H2S is firmly regulated by these enzymes under normal physiological conditions. Recent studies have highlighted the role of H2S in cellular redox homeostasis, as it displays significant antioxidant properties. H2S exerts antioxidant effects through several mechanisms, such as quenching reactive oxygen species (ROS) and reactive nitrogen species (RNS), by modulating cellular levels of glutathione (GSH) and thioredoxin (Trx-1) or increasing expression of antioxidant enzymes (AOE), by activating the transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2). H2S also influences the activity of the histone deacetylase protein family of sirtuins, which plays an important role in inhibiting oxidative stress in cardiomyocytes and during the aging process by modulating AOE gene expression. This review focuses on the role of H2S in NRF2 and sirtuin signaling pathways as they are related to cellular redox homeostasis.

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