Ferroptosis-centered Disease Response Information
General Information of the Disease (ID: DIS00145)
Name |
Myocardial injury
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ICD |
ICD-11: NB31
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Full List of Target(s) of This Ferroptosis-centered Disease
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | LPS-induced myocardial injury [ICD-11: NB31] | ||||
Responsed Drug | Pyridoxine | Approved | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Apoptosis | hsa04210 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
Cell apoptosis | |||||
In Vitro Model | CHO-S/H9C2 cells | Normal | Cricetulus griseus | CVCL_A0TS | |
In Vivo Model |
Male c57BL/6 mice (8 weeks old) were purchased from Beijing Wei Tong Li Hua Experimental Animal Technology Co. Ltd. (Beijing, China). Mice were divided into control (n = 8), LPS (n = 9), and VitB6+LPS (n = 9) groups. Mice were pretreated with PBS or VitB6 for 6 h and then treated with LPS (4 mg/kg) for 24 h. Cardiac ultrasound was performed before sacrifice. Inhaled isoflurane was given to mice for volatile anesthesia and the chest hair was removed with a depilatory cream. Then, mice were fixed on the warmed imaging platform and wore with the coupling agent. The Vevo2100 imaging system, equipped with a 40-MHz high-frequency transducer (VisualSonics Inc., Toronto, Canada), was applied to perform non-invasive examinations. The M-mode echocardiogram at the parasternal long axis was used to obtain the ejection fraction (EF) of left ventricular and fractional shortening (FS).
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Response regulation | Vitamin B6 (VitB6) is a water-soluble vitamin and includes pyridoxine, pyridoxal, pyridoxamine, and their phosphorylated forms. VitB6 regulated the expression of LPS-induced apoptosis-related proteins and iron regulatory proteins. It mediated the expression of Nrf2, transcription factor NF-E2-related factor 2, which promoted the expression of antioxidant enzymes and restrained LPS-induced ferroptosis and apoptosis. Overall, VitB6 can be used on novel therapies to relieve LPS-induced myocardial injury. | ||||
Cystine/glutamate transporter (SLC7A11)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [2] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Obesity-induced cardiac injury [ICD-11: NB31] | ||||
Responsed Regulator | hsa-miR-140-5p (miRNA) | Driver | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Fatty acid metabolism | hsa01212 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | CHO-S/H9C2 cells | Normal | Cricetulus griseus | CVCL_A0TS | |
In Vivo Model |
Six-week-old C57BL/6 male mice were randomly divided into two groups; the first group was fed a 45% high fat diet for 20 weeks while the control group were fed a normal chow diet. ATM-exosomes isolated from obese and lean mice were transferred into normal mice via tailvein injection(30 ug per week), as previously described. To investigate glutathione synthesis, 20 mM l-buthionine-(S,R)-sulfoximine (BSO) was added to the drinking water and administered to mice for 2 weeks. To inhibit ferroptosis, mice were given an intraperitoneal injection with Fer-1 (1 mg/kg).
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Response regulation | Solute carrier family 7 member 11 (SLC7A11) is a downstream target of miR-140-5p, which induces ferroptosis via inhibition of GSH synthesis by targeting SLC7A11. Attenuating exosomal-miR-140-5p expression alleviates ferroptosis and obesity-induced cardiac injury by alleviating GSH inhibition. | ||||
References