Autophagy markers as mediators of lung injury-implication for therapeutic intervention

Vishnupriya, Selvaraj; Dharshini, Loganathan Chandramani Priya; Sakthivel, Kunnathur Murugesan; Rasmi, Rajan Radha

doi:10.1016/j.lfs.2020.118308

Cited by 60 publications

(43 citation statements)

References 181 publications

(232 reference statements)

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“…Acute lung injury (ALI) and its worse form, acute respiratory distress syndrome (ARDS) consist of a set of pathological lung modifications that occur from pulmonary destructive events, such as pneumonia, sepsis, pulmonary trauma, viral infections and various other situations or diseases (116)(117)(118). Such phenomena deteriorate the vascular endothelium and the alveolar epithelium (119) resulting in loss of function of the corresponding cells due to excessive inflammation, hypoxemia and eventually respiratory failure (120,121). Both ALI and ARDS, due to the severe nature of their manifestations, are characterized by high mortality rates, despite the available treatment options that aim to optimize the diseases' outcome (116,122).…”

Section: Acute Lung Injury Acute Respiratory Distress Syndrome and Ace I/d Polymorphismmentioning

confidence: 99%

The Impact ofACEandACE2Gene Polymorphisms in Pulmonary Diseases Including COVID-19

Gintoni

Αδαμοπούλου

Yapijakis

2021

In Vivo

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Chronic and acute respiratory diseases pose a major problem for public health worldwide due to the high morbidity and mortality rates, while treatment options remain mostly symptomatic. The renin-angiotensin system (RAS) plays an important role in lung tissue, regulating pulmonary circulation and blood pressure, but also contributing to normal pulmonary function and development. Angiotensin-converting enzyme (ACE) and its homologous angiotensin-converting enzyme 2 (ACE2) are considered to be amongst the main RAS regulators and are highly expressed in the pulmonary vascular endothelium. This review discusses the impact of ACE and ACE2 functional gene polymorphisms on seven major pulmonary diseases, in terms of predisposition, course, and outcome, revealing their potential utility as both genetic markers and biomarkers. The discussed conditions include chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), asthma, acute lung injury (ALI), acute respiratory distress syndrome (ARDS), lung cancer and pulmonary sarcoidosis (PS), as well as SARS-CoV-2 viral infection and COVID-19 disease.Chronic respiratory diseases (CRDs) have been among the leading causes of morbidity and mortality around the globe for the last two decades (1-3). Their constantly increasing rates of occurrence may vary both between the genders, but also between different regions and socio-economic backgrounds (4). Nevertheless, the common denominator includes the deterioration of patients' quality of life that can often lead to several years of disability. The main CRDs are chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), asthma and lung cancer, with COPD alone being the third leading cause of death worldwide, as reported in 2010 (1,5,6).On the other hand, acute lung diseases with an infectional etiology, pose a significant threat not only to lung health but also to human life (7). A recent great example is the 2019 outbreak of the novel coronavirus strain SARS-CoV-2 in China, causing the extremely infectious disease COVID-19, that led to a global pandemic and to millions of deaths, mainly due to severe respiratory complications (8, 9). So far, therapeutic approaches are mainly symptomatic, while knowledge on the exact pathogenetic mechanisms for complex lung-diseases remains limited. Consequently, prevention is predominantly based on general lifestyle guidelines, whereas the establishment of a priori personalized preventive measures, according to an individual's genetic predisposition, is still in its infancy (1, 5). Nevertheless, there are important known genetic markers that may be utilized for their predictive value.The renin-angiotensin system (RAS), in addition to its great importance for the overall homeostasis of the body, through the regulation of blood pressure and electrolyte balance, has a strong tissue-specific expression in the respiratory tract and functions both autonomously and 13 This article is freely accessible online.

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Section: Acute Lung Injury Acute Respiratory Distress Syndrome and Ace I/d Polymorphismmentioning

confidence: 99%

The Impact ofACEandACE2Gene Polymorphisms in Pulmonary Diseases Including COVID-19

Gintoni

Αδαμοπούλου

Yapijakis

2021

In Vivo

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“…The effect is obvious when CA is 8 μ g/ml. At the same time, the autophagy protein LC3B [ 30 ] was detected, and the results showed it to be significantly inhibited when CA was 8 μ g/ml. Autophagy has a close relationship with anoxic microenvironment [ 31 ], but the further relationship requires further study in future experiments.…”

Section: Discussionmentioning

confidence: 99%

Cinnamaldehyde Downregulation of Sept9 Inhibits Glioma Progression through Suppressing Hif-1α via the Pi3k/Akt Signaling Pathway

Wang

Fu³

et al. 2022

Disease Markers

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Purpose. Cinnamaldehyde (CA) is the main ingredient in cinnamon, and it has been proven to have an inhibitory effect on many different tumor types. However, it lacks effect on glioma. This paper explores the effect CA has on glioma cells U87 and U251 at the cellular and molecular levels. Methods. The relationship between Hif-1α and Sept9 was found by CGGA. Cell Viability Assay (CCK8) was made to detect the proliferation ability. The scratch experiment and the transwell experiment were applied to the migration and invasion ability. Annexin V-FITC/PI were used to detect the cell apoptosis. Western blotting was used to determine the specified protein level. Results. Cell proliferation assay results revealed CA to inhibit the proliferation of glioma cells in a dose-dependent manner. It promoted apoptosis for upregulating the expression of Bax and downregulating the expression of Bcl-2. Wound Healing Assay and transwell test found CA to have anti-invasion ability and that it upregulated the expression of E-cadherin and downregulated the expressions of MMP-2 and MMP-9. The molecular mechanism was studied from a tumor microenvironment (TME) perspective. Pi3k inhibitor (LY294002) was used for interfering with cells, and the results found CA to demonstrate a similar effect. Hif-1α and Sept9 expressions were inhibited, and Akt and p-Akt were also inhibited. By using CoCl2 to make hypoxia, CA was discovered to inhibit the high expression of Hif-1α and Sept9, demonstrating a correlation with the Pi3k/Akt pathway. It is suggested that the mechanism of Sept9 under hypoxia regulation can be realized through the Pi3k/Akt pathway. Conclusions. This study proves for the first time that CA is an effective drug for inhibiting the proliferation of glioma through Sept9 and reveals Sept9 to be related to the Pi3k/Akt pathway in terms of tumor microenvironment, providing a molecular basis for the further study of CA in glioma treatment.

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“…SQSTM1 is known as an autophagy protein that is involved in ubiquitin-proteasome and autophagy-lysosome degradation processes [25]. Liu Y et al revealed that the relationship between Na, K-ATPase and autophagy-lysosome pathway requires the involvement of α1 subunit, and Na, K-ATPase α1 and AMPK may act as the "on" and "off" switch of autophagy pathway [26].…”

Section: Discussionmentioning

confidence: 99%

Identification of Different Proteins Binding to Na, K-ATPase α1 in LPS-Induced ARDS Cell Model by Proteomic Analysis

Wen

Long

Zhang

et al. 2022

Preprint

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Background: Acute respiratory distress syndrome (ARDS) is characterized by refractory hypoxemia caused by accumulation of pulmonary fluid, which is related to inflammatory cell infiltration, impaired tight junction of pulmonary epithelium and impaired Na, K-ATPase function, especially Na, K-ATPase α1 subunit. Up until now, the pathogenic mechanism at the level of protein during lipopolysaccharide- (LPS-) induced ARDS remains unclear.Methods: Using an unbiased, discovery and quantitative proteomic approach, we discovered the differentially expressed proteins binding to Na, K-ATPase α1 between LPS-A549 cells and Control-A549 cells. These Na, K-ATPase α1 interacting proteins were screened by co-immunoprecipitation (Co-IP) technology. Among them, some of the differentially expressed proteins with significant performance were identified and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The protein interaction network was constructed by the related Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Several differentially expressed proteins were validated by Western blot.Results: Of identified 1598 proteins, 89 were differentially expressed proteins between LPS-A549 cells and Control-A549 cells. Intriguingly, protein-protein interaction network showed that there were 244 significantly enriched co-expression among 60 proteins in the group control-A549. while the group LPS-A549 showed 43 significant enriched interactions among 29 proteins. The related GO and KEGG analysis found evident phenomena of ubiquitination and deubiquitination, as well as the pathways related to autophagy. Among proteins with rich abundance, there were several intriguing ones, including the deubiquitinase (OTUB1), the tight junction protein zonula occludens-1 (ZO-1), the scaffold protein in CUL4B-RING ubiquitin ligase (CRL4B) complexes (CUL4B) and the autophagy-related protein sequestosome-1 (SQSTM1).Conclusions: In conclusion, our proteomic approach revealed targets related to the occurrence and development of ARDS, being the first study to investigate significant differences in Na, K-ATPase α1 interacting proteins between LPS-induced ARDS cell model and control-A549 cell. These proteins may help the clinical diagnosis and facilitate the personalized treatment of ARDS.

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Autophagy markers as mediators of lung injury-implication for therapeutic intervention

Cited by 60 publications

References 181 publications

The Impact ofACEandACE2Gene Polymorphisms in Pulmonary Diseases Including COVID-19

The Impact ofACEandACE2Gene Polymorphisms in Pulmonary Diseases Including COVID-19

Cinnamaldehyde Downregulation of Sept9 Inhibits Glioma Progression through Suppressing Hif-1α via the Pi3k/Akt Signaling Pathway

Identification of Different Proteins Binding to Na, K-ATPase α1 in LPS-Induced ARDS Cell Model by Proteomic Analysis

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