Ferroptosis-centered Disease Response Information
General Information of the Disease (ID: DIS00066)
Name |
Depressive disorder
|
||||
---|---|---|---|---|---|
ICD |
ICD-11: 6A70
|
Full List of Target(s) of This Ferroptosis-centered Disease
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 2 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Depression [ICD-11: 6A70] | ||||
Responsed Drug | Sodium hydrosulfide | Investigative | |||
Responsed Regulator | Cystathionine beta-synthase (CBS) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | BV-2 cells | Normal | Mus musculus | CVCL_0182 | |
In Vivo Model |
Adult male 22-24 g C57BL/6J mice were purchased from the Vital River Laboratory Animal Technology Co., Ltd. Mice were randomly divided into four groups, the control group (CON group, n = 8), diabetes mellitus group (DM group, n = 8), DM + sodium hydrosulfide (DM + 5.6 mg/kg NaHS, n = 8) group, and CON + sodium hydrosulfide (CON + 5.6 mg/kg NaHS, n = 8) group. In this experiment, mice have received daily intraperitoneally injection of NaHS during the last 4 weeks. Then, all mice were tested by the open field test (OFT), elevated plus maze test (EPM test), forced swimming test (FST), and tail suspension test (TST).
Click to Show/Hide
|
||||
Response regulation | Sodium hydrosulfide (NaHS) ameliorated the ferroptosis via increasing the protein expressions of SLC7A11, glutathione peroxidase 4 (GPX4), and cystathionine -synthase (CBS), reducing the pro-inflammatory cytokines, decreasing the levels of Fe2+, MDA, ROS, and lipid ROS. In conclusion, NaHS did alleviate anxiety and depression. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [2] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Depression [ICD-11: 6A70] | ||||
Responsed Drug | Xiaoyaosan | Investigative | |||
Responsed Regulator | Phosphatidylethanolamine-binding protein 1 (PEBP1) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | mHTs (Mouse hippocampus tissues) | ||||
In Vivo Model |
The specific-pathogen free (SPF) male C57BL/6 mice (8-week-old, SCXK (Beijing) 2016-0006) were purchased from Beijing Vital River Laboratory Animal Technology Limited Company. A total of 48 mice were randomly assigned to 4 groups (n = 12): a control group (no stress + physiological saline), a CUMS group (CUMS + physiological saline), a Xiaoyaosan group (CUMS + Xiaoyaosan treatment) and a fluoxetine group (CUMS + fluoxetine treatment).
Click to Show/Hide
|
||||
Response regulation | The activation of ferroptosis might exist in the hippocampi of CUMS-induced mice. The PEBP1-GPX4-mediated ferroptosis could be involved in the antidepressant mechanism of Xiaoyaosan. It also implied that ferroptosis could become a new target for research into the depression mechanism and antidepressant drugs. | ||||
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 | [3] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Depression [ICD-11: 6A70] | ||||
Responsed Drug | Edaravone | Approved | |||
Responsed Regulator | NAD-dependent protein deacetylase sirtuin-1 (SIRT1) | Suppressor | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Fatty acid metabolism | hsa01212 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | hBCs (Brain cells) | ||||
In Vivo Model |
Male C57BL/6J mice (aged 7-8 weeks) and retired male CD-1 mice (aged 16-20 weeks) were obtained from the Experimental Animal Centre of Chongqing Medical University (Chongqing, China). The experimental animals were housed in cages under a 12 h light/12 h dark cycle (lights on at 8:00 a.m.), 60 ± 5% humidity, and a temperature of 23 ± 1 with access to water and food freely. All experimental procedures were conducted in accordance with the Ethics Committee of Chongqing Medical University. EDA was purchased from Sigma-Aldrich (St. Louis, USA) and was dissolved in Vehicle (NaCl, 0.9%) at a dosage of 10 mg/kg. EX527 (a Sirt1 inhibitor) and ML385 (a Nrf2 inhibitor) were obtained from MedChemExpress (New Jersey, USA).
Click to Show/Hide
|
||||
Response regulation | The inflammation and oxidative stress (OS) have been considered crucial components of the pathogenesis of depression. Edaravone possesses potent antidepressant and anxiolytic properties through Sirt1/Nrf2/HO-1/Gpx4 axis and Gpx4-mediated ferroptosis may play a key role in this effect. | ||||
References