Insight into the Double-Edged Role of Ferroptosis in Disease
Abstract
:1. Introduction
2. Diseases
2.1. Urinary System
2.1.1. Acute Kidney Injury (AKI)
2.1.2. Chronic Kidney Disease and Renal Tumors
2.1.3. Prostate Cancer (PCA)
2.2. Digestive System
2.2.1. Gastric Cancer (GC)
2.2.2. Pancreatic Cancer (PDAC)
2.2.3. Colorectal Cancer (CRC)
2.2.4. Hepatocellular Cancer (HCC)
2.2.5. Hepatic Fibrosis
2.3. Respiratory System
2.3.1. Radiation Lung Injury (RILI)
2.3.2. Non-Small Cell Lung Cancer (NSCLC)
2.4. Nervous System
2.4.1. Parkinson’s Disease (PD)
2.4.2. Alzheimer’s Disease (AD)
2.4.3. Glioma
2.5. Other Systems
2.5.1. Melanoma
2.5.2. Doxorubicin (DOX)-Induced Cardiomyopathy (DIC)
Numbers | Diseases | Molecules | Mechanisms |
---|---|---|---|
1 | AKI | HO-1 | HO-1 resistance to ferroptosis, and the specific cause remains to be studied [17] |
2 | PCA | DECR1 | DECR1 participates in redox homeostasis by regulating the balance between saturated and unsaturated phospholipids [30] |
3 | GC | CDO1 | CDO1 activates GSH to inhibit the production of ROS and LP [38] |
4 | PDAC | cytochrome c | Decreased mitochondrial membrane potential down-regulated cytochrome c and ROS levels [41] |
HSPA5 | HSPA5-GPX4 pathway [42] | ||
5 | CRC | GPX4 | Inhibition of GPX4 increases ROS and transferrin [49] |
6 | HCC | GSH | GSH regulates ferroptosis by HIC1/HNF4A regulating FUF/FDF [50] |
NRF2 | p62-Keap1-NRF2 pathway [53] | ||
7 | Hepatic fibrosis | HO-1 | Improvement of hepatic fibrosis by HO-1 induction of HSC ferroptosis [58] |
8 | RILI | GPX4 | Down-regulation of GPX4 increases ROS production [65] |
9 | NSCLC | System Xc- | Induced the ferroptosis of CDDP-resistant NSCLC by inhibiting System Xc- [68] |
10 | PD | P53 | P53 induces ferroptosis by regulating GSH metabolism and ROS levels [47] |
11 | AD | GPX4 | The decrease in GPX4 content increases FHL and decreases the antioxidant capacity of brain [81] |
12 | Glioma | ACSL4 and GPX4 | Inhibit ferroptosis by inhibiting ACSL4 to increase the production of GPX4 [87] |
13 | Melanoma | miRNA-137 | MiRNA-137 inhibits the production of MDA, ROS, and Fe2+ [89] |
14 | DIC | GPX4 and LP | DOX down-regulates GPX4 and produces LP while reducing Fe3+ to Fe2+ [95] |
15 | RCC | Hippo | Hippo pathway effector TAZ regulates ferroptosis sensitivity in RCC [25] |
3. Ferroptosis Inducers
3.1. Sorafenib
3.2. Erastin
3.3. Sulfasalazine (SAS)
3.4. Ras-Selective Lethal Small Molecule 3 (RSL3)
4. Ferroptosis Inhibitors
4.1. Ferrostatin-1 (Fer-1)
4.2. Baicalein
4.3. Others
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compounds or Drugs | Structures | Mechanisms |
---|---|---|
Erastin | | Induced ferroptosis by inhibiting System Xc- [1]. |
Imidazole-ketone- erastin | | Induced ferroptosis by inhibiting System Xc- [122]. |
SAS | | Induced ferroptosis by inhibiting GPX4 and System Xc- [123]. |
RSL3 | | Induced ferroptosis by inhibiting GPX4 [124]. |
Sorafenib | | Induced ferroptosis by inhibiting System Xc- [125]. |
FINO2 | | Induced ferroptosis by causing widespread lipid peroxidation including both indirect loss of GPX4 enzymatic function and directly oxidizes iron. |
FIN56 | | Induced ferroptosis by inducing post-translational GPX4 protein degradation [126]. |
Ferric ammonium citrate | | Induced ferroptosis by increasing iron abundance [2]. |
DPI compounds | | Induced ferroptosis by inhibiting System Xc- through depleting GSH [9]. |
Tert-butylhydroperoxide | Induced ferroptosis by inhibiting System Xc- through depleting GSH [127]. | |
Fer-1 | | Inhibited ferroptosis by inhibiting LP [2]. |
Baicalein | | Inhibited ferroptosis by inhibiting the accumulation of iron, LP, and GPX4 degradation [119,128]. |
DFO mesylate | | Inhibited ferroptosis by inhibiting the accumulation of iron. |
2, 2’-pyridine | | Inhibited ferroptosis by inhibiting the accumulation of iron [1]. |
CPX | | Inhibited ferroptosis by inhibiting the accumulation of iron [5]. |
Liproxstatin-1 | | Inhibited ferroptosis by inhibiting LP [129]. |
D-α-Tocopherol | | Inhibited ferroptosis by inhibiting LP. |
Vitamin E | C29H50O2 | Inhibited ferroptosis by inhibiting LP [130]. |
Lostoxin A | Inhibited ferroptosis by inhibiting LP. | |
Trolox | | Inhibited ferroptosis by inhibiting LP. |
BHT | | Inhibited ferroptosis by inhibiting LP. |
Pepstatin methyl ester | Inhibited ferroptosis by inhibiting LP. | |
NH4Cl | Inhibited ferroptosis by inhibiting LP [131]. | |
Puerarin | | Inhibited ferroptosis by inhibiting ROS production and Ca2+ influx [1]. |
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Zhang, L.; Jia, R.; Li, H.; Yu, H.; Ren, K.; Jia, S.; Li, Y.; Wang, Q. Insight into the Double-Edged Role of Ferroptosis in Disease. Biomolecules 2021, 11, 1790. https://doi.org/10.3390/biom11121790
Zhang L, Jia R, Li H, Yu H, Ren K, Jia S, Li Y, Wang Q. Insight into the Double-Edged Role of Ferroptosis in Disease. Biomolecules. 2021; 11(12):1790. https://doi.org/10.3390/biom11121790
Chicago/Turabian StyleZhang, Lei, Ruohan Jia, Huizhen Li, Huarun Yu, Keke Ren, Shuangshuang Jia, Yanzhang Li, and Qun Wang. 2021. "Insight into the Double-Edged Role of Ferroptosis in Disease" Biomolecules 11, no. 12: 1790. https://doi.org/10.3390/biom11121790