Focus on the Role of Calcium Signaling in Ferroptosis: a Potential Therapeutic Strategy for Sepsis-induced Acute Lung Injury

Overview

Journal Front Med (Lausanne)

Specialty General Medicine

Date 2024 Oct 2

PMID 39355841

Authors

Yifei Xu

Xintian Qu

Minghao Liang

Di Huang

Minyan Jin

Lili Sun

Xianhai Chen

Fen Liu

Zhanjun Qiu

Affiliations

Soon will be listed here.

Abstract

By engaging in redox processes, ferroptosis plays a crucial role in sepsis-induced acute lung injury (ALI). Although iron stimulates calcium signaling through the stimulation of redox-sensitive calcium pathways, the function of calcium signals in the physiological process of ferroptosis in septic ALI remains unidentified. Iron homeostasis disequilibrium in ferroptosis is frequently accompanied by aberrant calcium signaling. Intracellular calcium overflow can be a symptom of dysregulation of the cellular redox state, which is characterized by iron overload during the early phase of ferroptosis. This can lead to disruptions in calcium homeostasis and calcium signaling. The mechanisms controlling iron homeostasis and ferroptosis are reviewed here, along with their significance in sepsis-induced acute lung injury, and the potential role of calcium signaling in these processes is clarified. We propose that the development of septic acute lung injury is a combined process involving the bidirectional interaction between iron homeostasis and calcium signaling. Our goal is to raise awareness about the pathophysiology of sepsis-induced acute lung injury and investigate the relationship between these mechanisms and ferroptosis. We also aimed to develop calcium-antagonistic therapies that target ferroptosis in septic ALI and improve the quality of survival for patients suffering from acute lung injury.

References

Yan B, Ai Y, Sun Q, Ma Y, Cao Y, Wang J . Membrane Damage during Ferroptosis Is Caused by Oxidation of Phospholipids Catalyzed by the Oxidoreductases POR and CYB5R1. Mol Cell. 2020; 81(2):355-369.e10. DOI: 10.1016/j.molcel.2020.11.024. View

Krebs J, Agellon L, Michalak M . Ca(2+) homeostasis and endoplasmic reticulum (ER) stress: An integrated view of calcium signaling. Biochem Biophys Res Commun. 2015; 460(1):114-21. DOI: 10.1016/j.bbrc.2015.02.004. View

Dixon S, Lemberg K, Lamprecht M, Skouta R, Zaitsev E, Gleason C . Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012; 149(5):1060-72. PMC: 3367386. DOI: 10.1016/j.cell.2012.03.042. View

Guo N . Identification of as a biomarker and contributor of ferroptosis in clear cell renal cell carcinoma. Transl Cancer Res. 2022; 11(8):2688-2699. PMC: 9459583. DOI: 10.21037/tcr-21-2157. View

Cavezzi A, Menicagli R, Troiani E, Corrao S . COVID-19, Cation Dysmetabolism, Sialic Acid, CD147, ACE2, Viroporins, Hepcidin and Ferroptosis: A Possible Unifying Hypothesis. F1000Res. 2022; 11:102. PMC: 8921693. DOI: 10.12688/f1000research.108667.2. View

Wu T, Wang X, Cheng J, Liang X, Li Y, Chen M . Nitrogen-doped graphene quantum dots induce ferroptosis through disrupting calcium homeostasis in microglia. Part Fibre Toxicol. 2022; 19(1):22. PMC: 8944010. DOI: 10.1186/s12989-022-00464-z. View

Alpizar Y, Uvin P, Naert R, Franken J, Pinto S, Sanchez A . TRPV4 Mediates Acute Bladder Responses to Bacterial Lipopolysaccharides. Front Immunol. 2020; 11:799. PMC: 7218059. DOI: 10.3389/fimmu.2020.00799. View

Guan W, Xia M, Ji M, Chen B, Li S, Zhang M . Iron induces two distinct Ca signalling cascades in astrocytes. Commun Biol. 2021; 4(1):525. PMC: 8100120. DOI: 10.1038/s42003-021-02060-x. View

Marchi S, Patergnani S, Pinton P . The endoplasmic reticulum-mitochondria connection: one touch, multiple functions. Biochim Biophys Acta. 2013; 1837(4):461-9. DOI: 10.1016/j.bbabio.2013.10.015. View

10.

Meyer N, Gattinoni L, Calfee C . Acute respiratory distress syndrome. Lancet. 2021; 398(10300):622-637. PMC: 8248927. DOI: 10.1016/S0140-6736(21)00439-6. View

11.

Parthasarathi K . The Pulmonary Vascular Barrier: Insights into Structure, Function, and Regulatory Mechanisms. Adv Anat Embryol Cell Biol. 2017; 228:41-61. DOI: 10.1007/978-3-319-68483-3_3. View

12.

Knowles H, Li Y, Perraud A . The TRPM2 ion channel, an oxidative stress and metabolic sensor regulating innate immunity and inflammation. Immunol Res. 2012; 55(1-3):241-8. DOI: 10.1007/s12026-012-8373-8. View

13.

Wang Y, Chen D, Xie H, Jia M, Sun X, Peng F . AUF1 protects against ferroptosis to alleviate sepsis-induced acute lung injury by regulating NRF2 and ATF3. Cell Mol Life Sci. 2022; 79(5):228. PMC: 11072094. DOI: 10.1007/s00018-022-04248-8. View

14.

Peng Q, Zou Y, Zhang L, Ai M, Liu W, Ai Y . Blocking Cyclic Adenosine Diphosphate Ribose-mediated Calcium Overload Attenuates Sepsis-induced Acute Lung Injury in Rats. Chin Med J (Engl). 2016; 129(14):1725-30. PMC: 4960964. DOI: 10.4103/0366-6999.185854. View

15.

Lu Q, Zemskov E, Sun X, Wang H, Yegambaram M, Wu X . Activation of the mechanosensitive Ca channel TRPV4 induces endothelial barrier permeability via the disruption of mitochondrial bioenergetics. Redox Biol. 2020; 38:101785. PMC: 7691184. DOI: 10.1016/j.redox.2020.101785. View

16.

Yamamoto S, Shimizu S, Kiyonaka S, Takahashi N, Wajima T, Hara Y . TRPM2-mediated Ca2+influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration. Nat Med. 2008; 14(7):738-47. PMC: 2789807. DOI: 10.1038/nm1758. View

17.

Colas-Algora N, Millan J . How many cadherins do human endothelial cells express?. Cell Mol Life Sci. 2018; 76(7):1299-1317. PMC: 11105309. DOI: 10.1007/s00018-018-2991-9. View

18.

Sun Y, Yan C, He L, Xiang S, Wang P, Li Z . Inhibition of ferroptosis through regulating neuronal calcium homeostasis: An emerging therapeutic target for Alzheimer's disease. Ageing Res Rev. 2023; 87:101899. DOI: 10.1016/j.arr.2023.101899. View

19.

Riaz T, Junjappa R, Handigund M, Ferdous J, Kim H, Chae H . Role of Endoplasmic Reticulum Stress Sensor IRE1α in Cellular Physiology, Calcium, ROS Signaling, and Metaflammation. Cells. 2020; 9(5). PMC: 7290600. DOI: 10.3390/cells9051160. View

20.

Galy B, Conrad M, Muckenthaler M . Mechanisms controlling cellular and systemic iron homeostasis. Nat Rev Mol Cell Biol. 2023; 25(2):133-155. DOI: 10.1038/s41580-023-00648-1. View