Recent Progress of Ferroptosis in Lung Diseases

Shao, Yu; Jia, Jinqiu; Zheng, Jinyu; Zhou, Yiyang; Jia, Danyun; Wang, Junlu

doi:10.3389/fcell.2021.789517

Cited by 37 publications

(15 citation statements)

References 95 publications

(102 reference statements)

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“…Of note, ferroptosis, which denotes an iron-dependent, nonapoptotic mode of cell death characterized by an accumulation of lipid ROS at the cell membrane, was observed in several lung diseases, such as lung cancer. In addition, the generation of oxidative stress as a result of SSAT overexpression, induced lipid peroxidation, and cell death have also been reported in several studies [ 8 , 9 , 26 , 28 ].…”

Section: Involvement Of Ssat In Cellular Mechanismsmentioning

confidence: 84%

The Association between Spermidine/Spermine N1-Acetyltransferase (SSAT) and Human Malignancies

Tse

Ding

Wong

et al. 2022

IJMS

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Spermidine/spermine N1-acetyltransferase (SSAT) functions as a critical enzyme in maintaining the homeostasis of polyamines, including spermine, spermidine, and putrescine, in mammalian cells. SSAT is a catalytic enzyme that indirectly regulates cellular physiologies and pathways through interaction with endogenous and exogenous polyamines. Normally, SSAT exhibits only at a low cellular level, but upon tumorigenesis, the expression, protein level, and activities of SSAT are altered. The alterations induce cellular damages, including oxidative stress, cell cycle arrest, DNA dynamics, and proliferation by influencing cellular mechanisms and signaling pathways. The expression of SSAT has been reported in various studies to be altered in different cancers, and it has been correlated with tumor development and progression. Tumor grades and stages are associated with the expression levels of SSAT. SSAT can be utilized as a target for substrate binding, and excreted metabolites may be used as a novel cancer biomarker. There is also potential for SSAT to be developed as a therapeutic target. Polyamine analogs could increase SSAT expression and increase the cytotoxicity of chemotherapy to tumor cells. Drugs targeting polyamines and SSAT expression have the potential to be developed into new cancer treatments in the future.

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Section: Involvement Of Ssat In Cellular Mechanismsmentioning

confidence: 84%

The Association between Spermidine/Spermine N1-Acetyltransferase (SSAT) and Human Malignancies

Tse

Ding

Wong

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…With the progress of ferroptosis-related research, it has been revealed that ferroptosis plays a crucial role in many pathological changes in lung diseases. Among these findings, the dysregulation of ferroptosis in lung cancer has been more widely and deeply explored (Xu et al, 2021b;Yu et al, 2021). In this review, we provide a current understanding and views of ferroptosis in lung diseases, especially beyond lung cancer, from the aspects of the molecular basis and the corresponding therapeutic significance.…”

Section: Discussionmentioning

confidence: 95%

Multifaceted Roles of Ferroptosis in Lung Diseases

Yang

2022

Front. Mol. Biosci.

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Ferroptosis is a distinct type of programmed cell death (PCD) that depends on iron and is characterized by the accumulation of intracellular iron, exhaustion of glutathione, deactivation of glutathione peroxidase, and promotion of lipid peroxidation. Recently, accumulated investigations have demonstrated that ferroptosis is strongly correlated with the initiation and development of many lung diseases. In this review, we summarized the contribution of ferroptosis to the pathologic process of lung diseases, namely, obstructive lung diseases (chronic obstructive pulmonary disease, asthma, and cystic fibrosis), interstitial lung diseases (pulmonary fibrosis of different causes), pulmonary diseases of vascular origin (ischemia-reperfusion injury and pulmonary hypertension), pulmonary infections (bacteria, viruses, and fungi), acute lung injury, acute respiratory distress syndrome, obstructive sleep apnea, pulmonary alveolar proteinosis, and lung cancer. We also discussed the therapeutic potential of targeting ferroptosis for these lung diseases.

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“…Such an example would be Artemisia-derived drugs, used to treat malaria and considered in treating SARS-CoV-2 infected patients. Artesunate can increase the lysosomal degradation of intracellular ferritin with the release of free iron and oxidative stress, leading to the death of the infected cells (therapeutic induction of ferroptosis) [6,79,80]. Therefore, there is a clear need for more research to enable knowledge on the exact link between preexisting patient comorbidities, serum ferritin levels, and COVID-19.…”

Section: Future Perspectivesmentioning

confidence: 99%

Hyperferritinemia: the link between COVID-19, inflammation, and patient comorbidities

Lazăr

2021

jidhealth

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Ferritin is a key molecule in iron metabolism, as it stores the iron in a non-toxic form for the cells. Serum ferritin is a parameter that reflects the iron content of the body. However, serum ferritin is also an acute-phase reactant protein, as increased levels of serum ferritin are reported in many diseases associated with inflammation. Hyperferritinemia was also reported in COVID-19 (the coronavirus disease 19) patients, where it is considered an independent prognostic factor for the patients, indicating increased severity of the disease, risk for complications, and death. Certain categories of patients (older, those with comorbidities) have an increased risk of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infectivity and developing more severe forms of COVID-19. Chronic/acute systemic inflammatory states often characterize such preexisting comorbidities. In the current paper, a new pathogenic link is proposed and analyzed: between preexisting hyperferritinemia in the context of patient comorbidities (metabolic, cardiovascular, kidney, inflammatory, autoimmune, cancer) and the risk of SARS-CoV-2 infectivity and of developing more severe forms of infection. Ferritin per se can be a causal agent in COVID-19, as it can generate and aggravate inflammation and contributes to the development of a severe cytokine storm. A severe, uncontrolled inflammatory state occurs, triggered by the high levels of serum ferritin, preexisting comorbidities, and SARS-CoV-2 infection, cause of lethality in many patients. The inflammatory stimuli can further aggravate the infection by activating ADAM-17 (disintegrin and metalloprotease 17), a key enzyme involved in ACE2 (angiotensin-converting enzyme 2) activation and viral infectivity. In this context, iron chelators and antioxidants could become potential lines of treatment in COVID-19.

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Recent Progress of Ferroptosis in Lung Diseases

Cited by 37 publications

References 95 publications

The Association between Spermidine/Spermine N1-Acetyltransferase (SSAT) and Human Malignancies

The Association between Spermidine/Spermine N1-Acetyltransferase (SSAT) and Human Malignancies

Multifaceted Roles of Ferroptosis in Lung Diseases

Hyperferritinemia: the link between COVID-19, inflammation, and patient comorbidities

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