miR-130a alleviates neuronal apoptosis and changes in expression of Bcl-2/Bax and caspase-3 in cerebral infarction rats through PTEN/PI3K/Akt signaling pathway

Background: The effects of hydrogen-rich water on PI3K/AKT-mediated apoptosis were studied in rats subjected to myocardial ischemia-reperfusion injury (MIRI). Methdos: Sixty rats were divided randomly into a hydrogen-rich water group and a control group. The hearts were removed and fixed in a Langendorff device. Hearts from the control group were perfused with K-R solution, and hearts from the hydrogen-rich water group was perfused with K-R solution + hydrogen-rich water. The two treatment groups were then divided randomly into pre-ischemic period, ischemic period and reperfusion period groups(10 rats per group), which were subjected to reverse perfusion for 10 min, normal treatment for 20 min, and reperfusion for 20 min, respectively. The mRNA and protein expression levels of PI3K, AKT, p-AKT, FoxO1, Bim and Caspase-3 in each group were detected by RT-qPCR, immunohistochemistry (IHC) and Western blotting. Caspase-3 activity was detected by spectrophotometry. Results: Among the hydrogen-rich water group, the PI3K/AKT signaling pathway was significantly activated, and FoxO1, Bim, and Caspase-3 mRNA and protein levels were significantly decreased in ischemia-reperfusion subgroup compared with the preischemic and ischemic subgroups. In the ischemia-reperfusion hydrogen-rich water group, PI3K, AKT and p-AKT mRNA and protein expression levels were increased while the FoxO1, Bim and Caspase-3 expression levels were significantly decreased compared with those in the corresponding control group (p<0.05). Conclusion: Hydrogen-rich water can activate the PI3K/AKT signaling pathway, alleviate ischemia-reperfusion injury in isolated rat hearts, and inhibit cardiomyocyte apoptosis.

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Cordycepin enhances the chemosensitivity of esophageal cancer cells to cisplatin by inducing the activation of AMPK and suppressing the AKT signaling pathway

Cell Death and Disease ◽

10.1038/s41419-020-03079-4 ◽

2020 ◽

Vol 11 (10) ◽

Author(s):

Ying Gao ◽

Dan-Lei Chen ◽

Mi Zhou ◽

Zhou-san Zheng ◽

Mei-Fang He ◽

...

Keyword(s):

Esophageal Cancer ◽

Combination Therapy ◽

Cancer Cells ◽

Signaling Pathway ◽

Caspase 3 ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Expression Levels ◽

In Vivo Animal Model ◽

Esophageal Cancer Cells

Abstract Although cisplatin (cDDP), is a first-line chemotherapy drug for esophageal cancer, it still has the potential to develop drug resistance and side effects. There is increasing evidence that cordycepin can work synergistically with other chemotherapy drugs. Therefore, we investigated whether combination therapy of cordycepin and cDDP may enhance the therapeutic effect of cDDP. We performed a series of functional tests to study the effect of medical treatment on esophageal cancer cells. We then used GO analysis to examine the pathways affected by treatment with cordycepin and cDDP. Next, we observed changes in the abundance of the selected pathway proteins. The in vivo animal model supported the results of the in vitro experiments. Co-treatment with cordycepin and cDDP inhibited cell growth, migration, and metastasis, as well as induced apoptosis. Cordycepin was found to effectively enhance activation of AMPK and inhibited activity of AKT. In all treatment groups, the expression levels of p-PI3K, p-Akt, p-p70S6K, Caspase-3, and Bcl-2 were significantly reduced, while the expression levels of p-AMPK, cleaved Caspase-3, and Bax increased, and the total levels of Akt, PI3K, and p70S6K levels remained unchanged. Overall, cordycepin was found to enhance the chemical sensitivity of esophageal cancer cells to cisplatin by inducing AMPK activation and inhibiting the AKT signaling pathway. Combination therapy of cordycepin and cisplatin represent a novel potential treatment of esophageal cancer.

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Sevoflurane post-conditioning attenuates traumatic brain injury-induced neuronal apoptosis by promoting autophagy via the PI3K/AKT signaling pathway

Drug Design Development and Therapy ◽

10.2147/dddt.s158313 ◽

2018 ◽

Vol Volume 12 ◽

pp. 629-638 ◽

Cited By ~ 23

Author(s):

Hefan He ◽

Weifeng Liu ◽

Yingying Zhou ◽

Yibin Liu ◽

Peiqing Weng ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Signaling Pathway ◽

Neuronal Apoptosis ◽

Akt Signaling ◽

Akt Signaling Pathway

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Relaxin Attenuates Contrast-Induced Human Proximal Tubular Epithelial Cell Apoptosis by Activation of the PI3K/Akt Signaling Pathway In Vitro

BioMed Research International ◽

10.1155/2017/2869405 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Xiang-Cheng Xie ◽

Yizhi Cao ◽

Xiu Yang ◽

Qun-Hong Xu ◽

Wei Wei ◽

...

Keyword(s):

Acute Kidney Injury ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Caspase 3 ◽

Kidney Injury ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Bax Protein ◽

Phosphorylated Akt

Background. Contrast-induced acute kidney injury (CI-AKI) is one of the main causes of iatrogenic acute kidney injury (AKI); however, therapeutic strategies for AKI remain limited. This study aims to explore the effect of relaxin (RLX) on contrast-induced HK-2 apoptosis and its underlying mechanisms.Methods. Renal tubular epithelial cells (HK-2) were incubated either with or without ioversol, human H2 relaxin, and LY294002 (the inhibitor of the PI3K/Akt signal pathway). Cell viability was evaluated with a CCK-8 assay. Apoptotic morphologic alterations were observed using the Hoechst 33342 staining method. Apoptosis was detected with Annexin V staining. Western blot analysis was employed to measure the expression of pAkt (S473), Akt, cleaved caspase-3, Bcl-2, Bax, and actin proteins.Results. Ioversol reduced the viability of HK-2 cells. Western blotting results revealed decreased expression of phosphorylated Akt in cells treated with ioversol. The activities of caspase-3 and Bax protein increased, while the expression of Bcl-2 protein decreased. As a result, the Bax/Bcl-2 ratio increased after treatment with ioversol. These effects were reversed when HK-2 cells were cotreated with RLX. However, with preadministration of PI3K/Akt pathway inhibitor LY294002, the effect of RLX was blocked.Conclusion. Our study demonstrates that relaxin attenuates ioversol induced cell apoptosis via activation of the PI3K/Akt signaling pathway, suggesting that RLX might play a protective role in the treatment of CI-AKI.

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Phosphatidylinositol 3-kinase/Akt signaling stimulates colonic mucosal cell survival during aging

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00106.2005 ◽

2006 ◽

Vol 290 (1) ◽

pp. G49-G55 ◽

Cited By ~ 15

Author(s):

Adhip P. N. Majumdar ◽

Jianhua Du

Keyword(s):

Cell Survival ◽

Signaling Pathway ◽

Colonic Mucosa ◽

Caspase 3 ◽

Akt Signaling ◽

Entire Length ◽

Mucosal Cell ◽

Colonic Crypt ◽

Akt Signaling Pathway ◽

Age Related

Although aging is shown to be associated with decreased apoptosis and increased survival of cells in the colonic mucosa of Fischer 344 rats, the regulatory mechanisms are poorly understood. The current investigation examines the involvement of phosphotidylinositol 3-kinase (PI3K)/Akt signaling pathway in mediating the events of colonic mucosal cell survival during aging. We have observed that aging is associated with activation of PI3K/Akt signaling, as evidenced by the higher levels of phosphorylated forms of p85, the regulatory subunit of PI3K and of Akt in the proximal and distal colonic mucosa, of aged (21–23 mo) than in young (4–7 mo) rats. These increases are accompanied by a concomitant rise in phosphorylation of proapoptotic protein Bad, which is sequestered by the 14-3-3 family of proteins following phosphorylation by Akt, resulting in a reduction in nonphosphorylated Bad. The amount of antiapoptotic Bcl-xL bound to nonphosporylated Bad in the colonic mucosa is found to be substantially lower in aged than in young rats, resulting in a marked rise in the unbound/free form of Bcl-xL in the aging colon. The age-related activation of PI3K and the reduction in caspase-3 activity could be reversed by wortmannin, a specific inhibitor of PI3K. Increased levels of Bcl-xL and phosphorylated forms of Akt and Bad and reduction in caspase-3 activity were observed throughout the entire length of the colonic crypt of aged rats. We conclude that the constitutive activation of the PI3K/Akt-signaling pathway is partly responsible for the age-related increase in colonic mucosal cell survival. This is evident throughout the entire length of the colonic crypt.

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Vincosamide inhibits malignant behaviors of hepatocellular carcinoma cells by activating caspase-3 activity and blocking the PI3K/AKT signaling pathway

10.21203/rs.3.rs-28543/v1 ◽

2020 ◽

Author(s):

Mingyue Zhu ◽

Haipeng Feng ◽

Bo Lin ◽

Ying Zhou ◽

Yifeng Zheng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Signaling Pathway ◽

Caspase 3 ◽

Tumor Model ◽

Akt Signaling ◽

Migration And Invasion ◽

Mitochondrial Morphology ◽

Mouse Tumor ◽

Akt Signaling Pathway ◽

Hcc Cells

Abstract Background Vincosamide(Vinco) was first identified in the methanolic extract of the leaves of Psychotria leiocarpa, and Vinco has important anti-inflammatory effects and activity against cholinesterase. However, whether Vinco inhibits the malignant behaviors of hepatocellular carcinoma(HCC) cells is still unclear. In the present study, we explored the role of Vinco in suppressing the malignant behaviors of HCC cells. Methods MTT and trypan blue exclusion assays were applied to detect the proliferation and death of HCC cells; electron microscopy was performed to observe change in cellular mitochondrial morphology; scratch repair and Transwell assays were used to analyze the migration and invasion of HCC cells; the expression and localization of proteins were detected by laser confocal microscopy and Western blotting; and the growth of the cancer cells in vivo was assessed in a mouse tumor model. Results At a dose of 10–80 µg/ml, Vinco inhibited the proliferation of HCC cells and promoted their apoptosis in a time- and dose-independent manner but had little effect on normal liver cells. Additionally, 80 µg/ml Vinco significantly disrupted the morphology of mitochondria and suppressed the migration and invasion of HCC cells. The growth of HCC cells in the animal tumor model was significantly inhibited after treatment with Vinco (10 mg/kg/day) for 3 days. The results of the present study indicate that Vinco (10–80 µg/ml) plays novel roles in activating caspase-3, promoting the expression of PTEN, and inhibiting the phosphorylation of AKT(Ser 473) and mTOR (Thr2448) and that Vinco was able to also suppress the expression of CXCR4, Src, MMP9, EpCAM, Ras and Oct4 in HCC cells. Conclusions Vinco plays a role in inhibiting the malignant behaviors of HCC cells, and the molecular mechanism may involve in suppressing the expression of the growth-, metastasis-related factors Src, Ras, MMP9, EpCAM and CXCR4 and activating the activity of caspase-3. Vinco also blocks the PI3K/AKT signaling pathway. Thus, Vinco is an available chemotherapy for HCC patients.

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FGF-2 Attenuates Neuronal Apoptosis via FGFR3/PI3k/Akt Signaling Pathway After Subarachnoid Hemorrhage

Molecular Neurobiology ◽

10.1007/s12035-019-01668-9 ◽

2019 ◽

Vol 56 (12) ◽

pp. 8203-8219 ◽

Cited By ~ 7

Author(s):

Takeshi Okada ◽

Budbazar Enkhjargal ◽

Zachary D. Travis ◽

Umut Ocak ◽

Jiping Tang ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Signaling Pathway ◽

Neuronal Apoptosis ◽

Akt Signaling ◽

Akt Signaling Pathway

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

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2259 ◽

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.

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