Dataset Information

3-iodothyronamine inhibits apoptosis induced by myocardial ischemia reperfusion via the Akt/FoxO1 signaling pathway.

ABSTRACT:

Background

This study investigated the potential effects of 3-iodothyronamine (T1AM) on myocardial ischemia reperfusion injury (MIRI) and the underlying molecular mechanisms.

Methods

A total of 16 adult male Sprague-Dawley rats were randomly divided into 4 groups and administered the following: control [60% dimethyl sulfoxide (DMSO) and 40% saline, pH 7.4], T1AM (25 mg/kg), T1AM (50 mg/kg), or T1AM (100 mg/kg). The rectal temperatures of the rats were measured at different time points. A further 30 adult male Sprague-Dawley rats were randomized and divided into the following 3 groups (n=10 in each group): sham operation, ischemia/reperfusion (I/R), and I/R + T1AM. In the I/R and I/R + T1AM groups, the left anterior descending (LAD) coronary artery of the rats were occluded for 0.5 hour to induce myocardial ischemia, followed by reperfusion for 3 hours in the I/R group. The electrocardiography (ECG), cardiac function, and 2,3,5-triphenyltetrazolium chloride (TTC) staining were examined in rats to evaluate the myocardial injury. The differences in the expression of apoptosis-related and Akt-FoxO1 signaling-related proteins were determined via Western blot.

Results

This work verified that T1AM reduced the body temperature of rats in a dose-dependent manner. Additionally, T1AM improved cardiac function and decreased the infarction size caused by MIRI. T1AM reduced the expression of biochemical parameters and apoptosis of myocardial cells. In addition, after treatment with T1AM, the expression of Glut1, pFoxO1 and Akt were reduced, while the expression of FoxO1 and PPARα were increased significantly.

Conclusions

Pretreatment of cardiomyocytes with T1AM inhibited apoptosis and protected against ischemia reperfusion injury via the Akt/FoxO1 signaling pathway.

SUBMITTER: Zhou H

PROVIDER: S-EPMC8908142 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

3-iodothyronamine inhibits apoptosis induced by myocardial ischemia reperfusion via the Akt/FoxO1 signaling pathway.

Zhou Haiyan H Mo Lili L Huang Niwen N Zou Changchao C Li Chao C Lin Muzhi M Zhang Bei B Wei Bo B Li Ping P Si Xiaoyun X Chen Jingjing J Li Wei W Liu Xingde X Hu Bailong B

Annals of translational medicine 20220201 4

<h4>Background</h4>This study investigated the potential effects of 3-iodothyronamine (T1AM) on myocardial ischemia reperfusion injury (MIRI) and the underlying molecular mechanisms.<h4>Methods</h4>A total of 16 adult male Sprague-Dawley rats were randomly divided into 4 groups and administered the following: control [60% dimethyl sulfoxide (DMSO) and 40% saline, pH 7.4], T1AM (25 mg/kg), T1AM (50 mg/kg), or T1AM (100 mg/kg). The rectal temperatures of the rats were measured at different time po ...[more]

PMID: 35280406

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Project description:Reperfusion therapy after myocardial infarction may lead to myocardial injury, which can be complicated and exacerbated by diabetes. The existing therapeutic methods for myocardial ischemia-reperfusion injury (MIRI) in diabetic patients are not ideal. Oleoylethanolamide (OEA) has been found to have protective effects on diabetes and acute cerebral ischemia. This study aimed to determine whether OEA can alleviate MIRI in diabetic rats, and to explore the underlying mechanism. The model of diabetic rats with MIRI was established by blocking the left coronary artery for 30 min, followed by restoring blood flow stability for 120 min. The myocardial enzyme spectrum, area of MIRI, and expression levels of apoptosis-related proteins were detected. The results showed that OEA pretreatment could reduce myocardial infarction area, protect myocardial tissue structure, and reduce myocardial cell apoptosis in diabetic rats with MIRI. Meanwhile, the levels of creatine kinase (CK)-MB (CK-MB), lactate dehydrogenase (LDH), and malondialdehyde (MDA) were reduced, while superoxide dismutase (SOD) level was elevated. H9C2 cells were treated with high glucose and oxygen-glucose deprivation/reperfusion (OGD/R) to establish an in vitro model. Capsazepine (CPZ), an antagonist of transient receptor potential vanilloid subtype 1 (TRPV1), and LY294002, an inhibitor of PI3K, were used to treat H9C2 cells in vitro. Apoptosis level and the expression levels of apoptosis-related proteins were measured. It was found that OEA activated TRPV1 and the PI3K/Akt signaling pathway, downregulated the expression levels of apoptosis-related proteins (Bcl-2 and cleaved caspase-3), and ameliorated the apoptosis of H9C2 cells treated with high glucose and OGD/R. This study clarified that OEA, as a TRPV1 agonist, could reduce myocardial cell apoptosis by activating the PI3K/Akt signaling pathway in diabetic rats with MIRI. The findings may provide a theoretical basis for administration of OEA as a potential therapeutic agent into diabetic patients with MIRI.

Project description:To investigate the impact of LncRNA 93358 on ischemia-reperfusion induced myocardial cell apoptosis and the underlying mechanism. After being subjected to hypoxia for 4 h, three models of hypoxia-reoxygenation (H/R) with reoxygenation times of 8, 16, and 24 h were established. The expression of LncRNA 93358 was detected by qPCR, and the most suitable conditions were selected for subsequent experiments. The LncRNA 93358 knockout rat myocardial cells were established by transfecting with shRNA-93358 and identified by the RT-PCR assay, followed by constructing the in vitro H/R model. H/R myocardial cells were treated with blank medium (Model), shRNA-NC (LncRNA 93358 NC), shRNA-93358 (LncRNA 93358 knock), and shRNA-93358 + LY294002 (LncRNA 93358 knockout+LY294002), respectively. Normal myocardial cells treated with blank medium was taken as the control group. The cell cycle and apoptosis were analyzed by the flow cytometry. The level of cellular SOD and MDA was measured by the ELISA assay. The expression level of LncRNA 93358 was determined by the RT-PCR assay and Western blot assay was utilized to evaluate the expression level of AKT1, p-AKT1, mTOR, p-mTOR, bcl-2, and Bax. Compared to control, the expression of LncRNA 93358 in H9C2 cells was significantly increased under hypoxic conditions for 4 h followed by reoxygenation for 8 h/16 h. Moreover, the expression of LncRNA 93358 was relatively higher under hypoxic conditions for 4 h followed by reoxygenation for 16 h. Compared to control, significantly lower p-mTOR/mTOR and p-AKT1/AKT1 level was observed in the model group, accompanied by the elevated MDA level, declined SOD level, increased apoptotic rate, enhanced arrest at S phase, upregulated Bax, and downregulated Bcl-2. Compared to the model and LncRNA 93358 NC group, the expression level of p-mTOR/mTOR and p-AKT1/AKT1 was significantly promoted in the LncRNA 93358 knock group, accompanied by the declined MDA level, increased SOD level, reduced apoptotic rate, increased arrest at G0/G1 phase, downregulated Bax, and upregulated Bcl-2, which were dramatically reversed in the LncRNA 93358 knockout+LY294002 group. LncRNA 93358 aggravated the apoptosis of myocardial cells after ischemia-reperfusion by mediating the PI3K/AKT/mTOR pathway.

Dataset Information

3-iodothyronamine inhibits apoptosis induced by myocardial ischemia reperfusion via the Akt/FoxO1 signaling pathway.

Background

Methods

Results

Conclusions

Publications

3-iodothyronamine inhibits apoptosis induced by myocardial ischemia reperfusion via the Akt/FoxO1 signaling pathway.

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