scholarly journals Thyroid hormone mediates cardioprotection against postinfarction remodeling and dysfunction through the IGF-1/PI3K/AKT signaling pathway

2020 ◽  
Author(s):  
Bin Zeng ◽  
Xiaoting Liao ◽  
Lei Liu ◽  
Caixia Zhang ◽  
Huaiyu Ruan
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Diseases ◽  
Thyroid Hormone ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Left Ventricular ◽  
Sham Operation ◽  
Akt Signaling Pathway ◽  
Anti Inflammatory ◽  
Related Proteins

Abstract Background Severe cardiovascular diseases, such as myocardial infarction or heart failure, can alter thyroid hormone (TH) secretion and peripheral conversion, leading to low triiodothyronine (T3) syndrome. Accumulating evidence suggests that TH has protective properties against cardiovascular diseases and that treatment with TH can effectively reduce myocardial damage after myocardial infarction (MI). However, the potential mechanisms are not clear. This study was designed to investigate the effect of T3 pretreatment on cardiac function and pathological changes in mice subjected to MI and the underlying mechanisms. Methods Adult male C57BL/6 mice underwent surgical ligation of the left anterior descending coronary artery (LAD) (or sham operation) to establish a myocardial infarction model. T3, BMS-754807 (inhibitor of insulin-like growth factor-1 receptor (IGF-1R)) or vehicle was administered before surgery. Results Compared with the MI group, the T3 pretreatment group exhibited significant attenuation of the myocardial infarct area, inhibition of cardiomyocyte apoptosis and fibrosis, and improved left ventricular function after MI. In addition, T3 exhibited an enhanced potency to stimulate angiogenesis and exert anti-inflammatory effects by reducing the levels of serum inflammatory cytokines after myocardial infarction. However, all of these protective effects were inhibited by the IGF-1R inhibitor BMS-754807. Moreover, the protein expression of IGF-1/PI3K/AKT signaling-related proteins, such as IGF-1, IGF-1R, phosphorylated PI3K (p-PI3K) and p-AKT was significantly upregulated in MI mice that received T3 pretreatment, and BMS-754807 pretreatment blocked the upregulation of the expression of these signaling-related proteins. Conclusion T3 pretreatment can protect the heart against dysfunction post-MI through its anti-apoptotic, anti-fibrotic, anti-inflammatory and angiogenesis-stimulating effects, which may be mediated by the activation of the IGF-1/PI3K/AKT signaling pathway.

scholarly journals Thyroid hormone mediates cardioprotection against postinfarction remodeling and dysfunction through the IGF-1/PI3K/AKT signaling pathway

Life Sciences ◽  
2021 ◽  
Vol 267 ◽  
pp. 118977
Author(s):  
Bin Zeng ◽  
Xiaoting Liao ◽  
Lei Liu ◽  
Caixia Zhang ◽  
Huaiyu Ruan ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Postinfarction Remodeling

Araloside C Prevent Myocardial Cell Apoptosis Through Regulating PI3K/AKt to Relieve Heart Failure

2021 ◽  
Author(s):  
Xingsheng Zhao ◽  
Yu Ren ◽  
Hongkun Ren ◽  
Yun Wu ◽  
Xi Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Myocardial Cell ◽  
Akt Signaling ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Akt Signaling Pathway ◽  
Ventricular Ejection Fraction ◽  
Wide Range ◽  
Index Level

Abstract Background Araloside C (AsC), a natural saponin isolated from Aralia elata, has a wide range of anti-inflammatory properties and has been found in recent years to have heart-protective effects. Present study aimed to determine the effects of AsC on myocardial cell apoptosis through regulating PI3K/AKt. Methods and Results Statistical analyses were performed using GraphPadPrism7.0 software. The differences between two groups and multiple groups were analyzed using t-test and one-way ANOVA, respectively. In vivo results showed that AsC administration could improve cardiac functions and apoptotic rate in HF model through PI3K/AKt signaling pathway, including increasing left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS), and decreasing left ventricular end systolic diameter (LVESD) and left ventricular end diastolic diameter (LVEDD) in detection of myocardial function, inhibiting LDH, CK, CK-MB, CK and HBDH in biochemical index level assessment, inhibiting BNP, ANG II, IL-1b, IL-4, IL-6 and TNF-a in immunological index level. ASC regulates the expression of key apoptotic molecules, including increasing the expression of Bcl-2 and Bax. ASC also regulates phosphorylation of p-PI3K and p-Akt.Conclusion This study suggested for the first time that AsC could partially regulate the PI3K/AKt signaling pathway to prevent myocardial cell apoptosis. This study provided a basis for further research on effective substances in the treatment of HF.

Effect of PI3K/Akt Signaling Pathway on PRAS40Thr246 Phosphorylation in Gastric Cancer Cells

2020 ◽  
Author(s):  
Yizhuo LU ◽  
Lianghui LI ◽  
Guoyang WU ◽  
Huiqin ZHUO ◽  
Guoyan LIU ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Cell Group ◽  
Akt Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Pathway Activation ◽  
Related Proteins ◽  
Proliferation And Invasion

Background: We aimed to investigate the effect of PI3K/Akt signaling pathway on PRAS40Thr246 phosphorylation in gastric cancer cells. Methods: The study was conducted from April 2017 to January 2018 in Zhongshan Hospital, Xiamen University, Xiamen, China. Gastric cancer cells were divided into three groups: gastric cancer cell group, LY294002 group and MK-2206 group. Specific tests were conducted accordingly. Results: Inhibition of PI3K/Akt signaling pathway activation and PRAS40Thr246 phosphorylation could inhibit proliferation and invasion and promote apoptosis of gastric cancer cells, and PRAS40Thr246 phosphorylation could activate PI3K/Akt signaling pathway. Conclusion: The levels of PI3K/Akt signaling pathway related proteins and p-PRAS40Thr246 were significantly increased in gastric cancer cells. p-PRAS40-Thr246 was able to reflect the activation of the PI3K/Akt signaling pathway, reflecting the sensitivity of the PI3K/AKT signaling pathway to inhibitors.

Effects of Promethazine on Proliferation and Apoptosis of Myocardial Cells in Rats with Myocardial Ischemia-Reperfusion Injury Through PI3K/Akt Signaling Pathway

2020 ◽  
Vol 10 (4) ◽  
pp. 477-481
Author(s):  
Hong Bing Xiao ◽  
Wei Hu ◽  
Jun Gu ◽  
Dandan Li
Keyword(s):  
Signaling Pathway ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
Left Ventricular ◽  
Drug Group ◽  
Control Group ◽  
Myocardial Cells ◽  
Akt Signaling Pathway ◽  
Ischemia Group

Objective: To assess promethazine's effect on myocardial cells in rats with myocardial ischemiareperfusion injury (MIRI). Methods: The rat MIRI model was established and treated as the ischemia group. MIRI rats were treated with promethazine and included as the drug group. Rats only undergoing thoracotomy were enrolled as the control group. The physiological function of heart was assessed using the ultrasound cardiotachograph, and the apoptosis and proliferation of myocardial cells were detected using TUNEL assay and Ki67 staining, respectively. Moreover, the expressions of Caspase-3, Bcl-2, PI3K, GSK-3, PDK-1 and PKB were determined via Western blotting and qPCR. Results: There were significant differences in cardiac function indexes [left ventricular enddiastolic diameter (LVEDd), left ventricular end systolic diameter (LVESd), ejection fraction (EF) and fractional shortening (FS)] among the three groups (p= 0 002, 0.004, 0.025 and 0.012), and ischemia group had the highest LVEDd [(8.73± 0.31) mm] and LVESd [(7.98± 0.37) mm] and lowest EF [(42± 3.8)%] and FS [(40.3± 2.8)%]. The number of apoptotic myocardial cells was significant higher in ischemia group than control ( p< 0 05), while it was significantly declined after treatment with promethazine ( p< 0 05). Caspase-3 was significantly upregulated and Bcl-2 was downregulated in ischemia group which were all significantly reversed in drug group. Besides, Ki67 level was significantly reduced in ischemia group compared to control and higher in drug group than ischemia group, indicating that drug treatment increased cell proliferation ability. The levels of PI3K, GSK-3 and PKB in myocardial tissues were significantly declined in ischemia group and elevated after the treatment with promethazine without difference of PDK-1 level in myocardial tissues among the three groups. Conclusion: Promethazine inhibits apoptosis and promotes proliferation of myocardial cells in MIRI rats through PI3K/Akt signaling pathway.

scholarly journals Paris polyphylla 26 triggers G2/M phase arrest and induces apoptosis in HepG2 cells via inhibition of the Akt signaling pathway

2019 ◽  
Vol 47 (4) ◽  
pp. 1685-1695
Author(s):  
Qiang Li ◽  
Zifan He ◽  
Jiming Liu ◽  
Jianlong Wu ◽  
Guixiang Tan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Signaling Pathway ◽  
Hepg2 Cells ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Phase Arrest ◽  
Paris Polyphylla ◽  
M Phase ◽  
Related Proteins

Objectives Paris polyphylla 26 (PP-26) is a monomer purified from Paris polyphylla, which has traditionally been used as an antimicrobial, hemostatic, and anticancer agent in China. The anti-proliferation effect and underlying molecular mechanism of PP-26 were investigated in vitro. Methods The effects of PP-26 on various tumor cells were detected by MTT assay. PP-26-affected cell cycle and cell cycle-related proteins in HepG2 cells were detected by flow cytometry and western blotting, respectively. Apoptosis in response to PP-26 was assessed by Hoechst 33258 staining and flow cytometry. PP-26-affected apoptosis-related proteins and Akt signaling were detected by western blotting. The inhibitory effect of PP-26 on HepG2 cells, when combined with 5-fluorouracil (5-FU), was also assessed. Results PP-26 inhibited proliferation of HepG2 cells in a dose-dependent manner by triggering G2/M-phase arrest. Moreover, PP-26 induced apoptosis of HepG2 cells. Expression levels of apoptosis proteins caspase 9, caspase 3, PARP, Bcl-2, Bcl-xL, and Mcl-1 were downregulated, while the expression level of apoptosis protein Bax was upregulated. Expression levels of p-Akt, p-GSK-3β, and p-Foxo3 were downregulated. Combination with PP-26 enhanced 5-FU inhibition of HepG2 cell proliferation. Conclusions PP-26 triggers G2/M-phase arrest and induces apoptosis in HepG2 cells via inhibition of the Akt signaling pathway.

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