scholarly journals Molecular Studies on the Nephroprotective Potential of Celastrus paniculatus against Lead-Acetate-Induced Nephrotoxicity in Experimental Rats: Role of the PI3K/AKT Signaling Pathway

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6647
Author(s):  
Karunakaran Balaji ◽  
Jagadish Vijayakumar ◽  
Ponnusamy Kasirajan Sankaran ◽  
Sivanesan Senthilkumar ◽  
Rajagopalan Vijayaraghavan ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Lead Acetate ◽  
Akt Signaling ◽  
Seed Extract ◽  
Control Group ◽  
Renal Tubules ◽  
Mrna Levels ◽  
Akt Signaling Pathway ◽  
Standard Drug ◽  
Celastrus Paniculatus

Chemicals can induce nephrotoxicity, with damage to different segments of the nephron and deterioration of renal function. Nephrotoxicity due to exposure to a toxin such as carbon tetrachloride, sodium oxalate, or heavy metals is the most common cause of kidney injury. The current study aimed to evaluate the protective effects of Celastrus paniculatus seed extract against lead-acetate-induced nephrotoxicity by evaluating the histopathology, immunohistochemistry, ultrastructure, and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Twenty-four rats were divided into four groups (n = 6 per group): group 1 contained normal animals and served as the control; group 2 received lead acetate (30 mg/kg body weight (b.w.)/day, oral); group 3 received lead acetate and the standard drug N-acetylcysteine (NAC, 200 mg/kg b.w./day, oral); and group 4 received lead acetate and the ethanolic extract of C. paniculatus seed (EECP; 800 mg/kg b.w./day, oral). Treatment was given for 28 consecutive days. The data were analyzed using one-way analysis of variance with SIGMA PLOT 13 using SYSTAT software followed by Newman–Keul’s test for comparison between the groups. EECP ameliorated the adverse changes caused by lead acetate. PI3K and AKT messenger RNA (mRNA) levels were diminished in lead-acetate-treated rats. Treatment with EECP inhibited the occurrence of shrunken cells, the atrophy of glomeruli, and degenerative changes in renal tubules caused by lead acetate. Interestingly, the PI3K and AKT mRNA levels were significantly increased in EECP-treated animals. Our results clearly evidence for the first time that C. paniculatus seed extract inhibits lead-acetate-induced detrimental changes in kidneys by regulating PI3K/AKT signaling pathways.

scholarly journals Hyperinsulinemia Can Cause Kidney Disease in the IGT Stage of OLETF Rats via the INS/IRS-1/PI3-K/Akt Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yi Zhang ◽  
Shaohua Yang ◽  
Xiao Cui ◽  
Juhong Yang ◽  
Miaoyan Zheng ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Glucose Tolerance ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Control Group ◽  
Renal Tubules ◽  
Akt Signaling Pathway ◽  
Oletf Rats ◽  
Renal Structure ◽  
Renal Tubular

Aims. We investigated the changes of renal structure and its function in normal glucose tolerance (NGT), impaired glucose tolerance (IGT), diabetes mellitus (DM), and diabetic kidney disease (DKD) stages in OLETF rats and explored the role of the INS/IRS-1/PI3-K/Akt signaling pathway. Methods. OLETF rats were assigned into four groups on the basis of OGTT results and 24 h urinary microalbumin: NGT, IGT, DM, and DKD groups. The changes of renal structure and function and the corresponding pathological changes were observed. The absorption of albumin and the expression of megalin, cubilin, IRS-1, PI3-K, and Akt in NRK-52E cells were measured after being stimulated by different concentrations of insulin. Results. In the IGT group, the index which reflects the function of renal tubule-like N-acetyl-β-glucosaminidase, neutrophil gelatinase-associated lipocalin, retinol-binding protein, and cystatin C was higher than those in the control group and the NGT group (P<0.05). Significant renal structure damages, especially in renal tubules, were observed in the IGT group. In the presence of insulin at a high concentration, the IRS-1/PI3-K/Akt signaling pathway in renal tubular epithelial cells was inhibited, and the expression of megalin and cubilin was significantly downregulated which was accompanied by a minimum uptake of albumin. Conclusions. In contrast to DKD, the renal structural damage and functional changes in the IGT stage, in which we propose the term “IGT kidney disease,” mainly manifest as renal tubular injury. Insulin resistance and compensatory hyperinsulinemia may be involved in its pathogenesis.

scholarly journals Astragaloside positively regulated osteogenic differentiation of pre-osteoblast MC3T3-E1 through PI3K/Akt signaling pathway

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Wei Bing Jing ◽  
Hongjuan Ji ◽  
Rui Jiang ◽  
Jinlong Wang
Keyword(s):  
Western Blot ◽  
Osteogenic Differentiation ◽  
Real Time ◽  
Signaling Pathway ◽  
Real Time Pcr ◽  
Akt Signaling ◽  
Calcium Deposition ◽  
Control Group ◽  
Akt Signaling Pathway ◽  
Western Blot Assay

Abstract Background Osteoporosis is a widespread chronic disease characterized by low bone density. There is currently no gold standard treatment for osteoporosis. The aim of this study was to explore the role and mechanism of Astragaloside on osteogenic differentiation of MC3T3-E1 cells. Methods MC3T3-E1 cells were divided into control and different dose of Astragaloside (10, 20, 40, 50, and 60 μg/ml). Then, ALP and ARS staining were performed to identify the effects of Astragaloside for early and late osteogenic capacity of MC3T3-E1 cells, respectively. Real-time PCR and western blot were performed to assess the ALP, OCN, and OSX expression. PI3K/Akt signaling pathway molecules were then assessed by Western blot. Finally, PI3K inhibitor, LY294002, was implemented to assess the mechanism of Astragaloside in promoting osteogenic differentiation of MC3T3-E1 cells. Results Astragaloside significantly increased the cell viability than the control group. Moreover, Astragaloside enhanced the ALP activity and calcium deposition than the control groups. Compared with the control group, Astragaloside increased the ALP, OCN, and OSX expression in a dose-response manner. Western blot assay further confirmed the real-time PCR results. Astragaloside could significantly increase the p-PI3K and p-Akt expression than the control group. LY294002 partially reversed the promotion effects of Astragaloside on osteogenic differentiation of MC3T3-E1 cells. LY294002 partially reversed the promotion effects of Astragaloside on ALP, OCN, and OSX of MC3T3-E1 cells. Conclusion The present study suggested that Astragaloside promoted osteogenic differentiation of MC3T3-E1 cells through regulating PI3K/Akt signaling pathway.

Effects of Hydrogen-rich Water on the PI3K/AKT Signaling Pathway in Rats with Myocardial Ischemia-reperfusion Injury

2020 ◽  
Vol 20 (5) ◽  
pp. 396-406 ◽  
Author(s):  
Liangtong Li ◽  
Xiangzi Li ◽  
Zhe Zhang ◽  
Li Liu ◽  
Tongtong Liu ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
Control Group ◽  
Akt Signaling Pathway ◽  
Expression Levels ◽  
Water Group

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.

scholarly journals Analysis of microRNA Expression after Glutamine Intervention in Acute Renal Ischemia-Reperfusion Injury

2022 ◽  
Vol 2022 ◽  
pp. 1-7
Author(s):  
Suhua Li ◽  
Xuan Huang ◽  
Shun Wang ◽  
Xueqian Chu ◽  
Munire Aierken
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Ischemia Reperfusion Injury ◽  
Rat Kidney ◽  
Ischemia Reperfusion ◽  
Kidney Tissue ◽  
Akt Signaling ◽  
Protective Mechanism ◽  
Renal Tubules ◽  
Akt Signaling Pathway

Background. Ischemia-reperfusion acute kidney injury (I/R AKI) is a severe kidney disease with high mortality and morbidity. This study aimed to explore the protective mechanism of glutamine (GLN) against I/R AKI. Methods.The I/R AKI rat model was established, and HE staining of kidney tissue and serum creatinine (SCr) and blood urea nitrogen (BUN) detection were performed. The miRNAs were sequenced by high throughput in rat kidney tissue samples. Differentially expressed miRNAs (DEmiRs) between the I/R group and I/R + GLN group were screened, and enrichment analysis for target genes of DEmiRs was performed. Meanwhile, human HK-2 cells were cultured, and an I/R model was established to verify the expression of DEmiRs. Results. Compared with the I/R group, the SCr and BUN levels at each time point were lower in the I/R + GLN group. Vacuolar degeneration of renal tubules in the I/R + GLN group was significantly reduced. In the 104 DEmiRs, we selected miR-132-5p, miR-205, and miR-615 as key miRNAs. KEGG analysis showed that the Notch signaling pathway, PI3K-Akt signaling pathway, and cGMP signaling pathway were mainly related to the GLN against I/R. qRT-PCR verified the downregulation of miR-205 in the I/R group, compared to the sham and I/R + GLN group. The I/R model was established with HK-2 cells, and the expression of miR-132-5p and miR-205 was decreased. Conclusion. GLN reduced I/R-induced AKI. There were significant differences between miRNAs expression in I/R after GLN treatment. The process of GLN against I/R-induced AKI may be related to the Notch and PI3K-Akt signaling pathway.

scholarly journals Molecular mechanisms of hydrogen sulfide against uremic accelerated atherosclerosis through cPKCβII/Akt signal pathway

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Ruifang Xiong ◽  
Xiangxue Lu ◽  
Jinghong Song ◽  
Han Li ◽  
Shixiang Wang
Keyword(s):  
Hydrogen Sulfide ◽  
Signaling Pathway ◽  
Sham Group ◽  
Akt Signaling ◽  
Signal Pathway ◽  
Control Group ◽  
Akt Signaling Pathway ◽  
Membrane Translocation ◽  
Enos Expression ◽  
Akt Phosphorylation

Abstract Background Cardiovascular disease is the most common complication and leading cause of death in maintenance hemodialysis patients. The protection mechanism of hydrogen sulfide (H2S) and the specific role of conventional protein kinase C βII (cPKCβII)/Akt signaling pathway in the formation of atherosclerosis is still controversial. Methods 8-week-old male ApoE−/− mice were treated with 5/6 nephrectomy and high-fat diet to make uremia accelerated atherosclerosis (UAAS) model. Mice were divided into normal control group (control group), sham operation group (sham group), UAAS group, L-cysteine group (UAAS+L-cys group), sodium hydrosulfide group (UAAS+NaHS group), and propargylglycine group (UAAS+PPG group). Western blot was used to detect cPKCβII activation, Akt phosphorylation and endothelial nitric oxide synthase (eNOS) expression in mice aorta. Results The membrane translocation of cPKCβII in UAAS group was higher than sham group, and L-cys or NaHS injection could suppress the membrane translocation, but PPG treatment resulted in more membrane translocation of cPKCβII (P < 0.05, n = 6 per group). Akt phosphorylation and the eNOS expression in UAAS group was lower than sham group, and L-cys or NaHS injection could suppress the degradation of Akt phosphorylation and the eNOS expression, but PPG treatment resulted in more decrease in the Akt phosphorylation and the eNOS expression (P < 0.05, n = 6 per group). Conclusion Endogenous cystathionine-γ-lyase (CSE)/H2S system protected against the formation of UAAS via cPKCβII/Akt signal pathway. The imbalance of CSE/H2S system may participate in the formation of UAAS by affecting the expression of downstream molecule eNOS, which may be mediated by cPKCβII/Akt signaling pathway.

Effects and Mechanisms of Tripartite Motif Containing 14 Downregulation on Proliferation, Migration, and Invasion of Cancerous Pancreatic PANC-1 Cells

2021 ◽  
Vol 11 (3) ◽  
pp. 402-406
Author(s):  
Huaping Gong ◽  
Long Chen ◽  
Ruipeng Dong
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Cellular Proliferation ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Control Group ◽  
Akt Signaling Pathway ◽  
Sirna Transfection ◽  
Akt Phosphorylation

This study aimed to investigate the effect and mechanism of TRIM14 downregulation on the apoptosis, migration, and invasion of cancerous pancreatic PANC-1 cells. PANC-1 cells cultured in vitrowere classified to a control (normal culture), negative (neutral siRNA transfection), and siTRIM14 group (TRIM14 siRNA transfection). RT-PCR was adopted to test TRIM14 mRNA expression. Cellular proliferation was determined by CCK-8, and transwell chamber invasion and apoptosis by flow cytometry. AKT signaling pathway related proteins CyclinD1, MMP-2, Bcl-2, and AKT phosphorylation, and TRIMI14 protein expression, were determined by western blotting. Compared with the control group, TRIMI14 expression, cellular proliferation ability, infiltration, transfer AKT phosphorylation, and TRIMI14, CyclinD1, MMP-2, and Bcl-2 protein expression were greatly reduced in siTRIM14 cells, and the apoptotic ability was significantly enhanced (P < 0.05). However, no striking differences were detected between the negative and control groups (P > 0.05). Downregulating TRIM14 expression can inhibit the proliferation, invasion, and migration of PANC-1 cells, and promote apoptosis. The mechanism may be associated with the inhibition of AKT signaling pathway activation.

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 Hyperoside Protects Against Pressure Overload-Induced Cardiac Remodeling via the AKT Signaling Pathway

2018 ◽  
Vol 51 (2) ◽  
pp. 827-841 ◽  
Author(s):  
Xiaofang Wang ◽  
Yuan Liu ◽  
Lili Xiao ◽  
Ling Li ◽  
Xiaoyan Zhao ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Cardiac Remodeling ◽  
Molecular Mechanisms ◽  
Pressure Overload ◽  
Akt Signaling ◽  
Neonatal Rat ◽  
Control Group ◽  
Akt Signaling Pathway

Background/Aims: Cardiac hypertrophy is a major predisposing factor for heart failure and sudden cardiac death. Hyperoside (Hyp), a flavonoid isolated from Rhododendron ponticum L., is a primary component of Chinese traditional patent medicines. Numerous studies have shown that Hyp exerts marked anti-viral, anti-inflammatory, anti-oxidant, anti-cancer, anti-ischemic, and particularly cardio-protective effects. However, the effects of Hyp on cardiac hypertrophy have not been explored. The aims of this study were to determine whether Hyp could protect against cardiac remodeling and to clarify the potential molecular mechanisms. Methods: Neonatal rat cardiac myocytes were isolated and treated with different concentrations of Hyp, then cultured with angiotensin II for 48 h. Mice were subjected to either aortic banding or sham surgery (control group). One week after surgery, the mice were treated with Hyp (20 mg/kg/day) or vehicle by oral gavage for 7 weeks. Hypertrophy was evaluated by assessing morphological changes, echocardiographic parameters, histology, and biomarkers. Results: Hyp pretreatment suppressed angiotensin II-induced hypertrophy in cardiomyocytes. Hyp exerted no basal effects but attenuated cardiac hypertrophy and dysfunction, fibrosis, inflammation, and oxidative stress induced by pressure overload. Both in vivo and in vitro experiments demonstrated that the effect of Hyp on cardiac hypertrophy was mediated by blocking activation of the AKT signaling pathway. Conclusion: Hyp improves cardiac function and prevents the development of cardiac hypertrophy via AKT signaling. Our results suggest a protective effect of Hyp on pressure overload-induced cardiac remodeling. Taken together, Hyp may have a role in the pharmacological therapy of cardiac hypertrophy.

scholarly journals CXCL12 Regulates the Cholinergic Locus and CHT1 Through Akt Signaling Pathway

2016 ◽  
Vol 40 (5) ◽  
pp. 982-992 ◽  
Author(s):  
Jing Yan ◽  
Wenhui Zhao ◽  
Meixia Guo ◽  
Xuefei Han ◽  
Zhiwei Feng
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Choline Acetyltransferase ◽  
Cholinergic Neurons ◽  
Akt Signaling ◽  
Neuronal Cultures ◽  
Mrna Levels ◽  
Akt Signaling Pathway ◽  
The Impact ◽  
And Storage

Background: CXCL12 is pivotal for cholinergic neurons, and it induces the expressions of several genes that are essential for synthesis and storage of acetylcholine(ACh), specifically choline acetyltransferase, vesicular ACh transporter (VAChT), and choline transporter. The present study explored the impact of pharmacological Akt inhibition upon cholinergic gene expression. Methods: Western blotting was employed to determine the level of p-AKT, RT-PCR to check the mRNA levels of and CHT1(choline transporter1),VAChT and ChAT, ELISA to decipher the secretion of ACh and the activity of choline acetyltransferase. Results: Here we demonstrated, in the rat pheochromocytoma cell line PC12 and in primary rat neuronal cultures, that CXCL12-evoked up-regulation of CHT1, VAChT and ChAT was mediated by Akt. Inhibition of Akt by the pharmacological inhibitor GSK690693 eliminated CXCL12-stimulated increases in cholinergic gene expression. Moreover, treatment with GSK690693 reversed CXCL12-evoked increases in choline acetyltransferase activity and ACh production. Conclusion: Our results suggest that CXCL12 contributes to cholinergic gene expression via Akt signaling pathway.

scholarly journals Berberine Sensitizes Human Ovarian Cancer Cells to Cisplatin Through miR-93/PTEN/Akt Signaling Pathway

2015 ◽  
Vol 36 (3) ◽  
pp. 956-965 ◽  
Author(s):  
Qiaoyun Chen ◽  
Rong Qin ◽  
Yue Fang ◽  
Hao Li
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Ovarian Cancer Cell Line ◽  
Akt Signaling ◽  
Ovarian Cancer Cells ◽  
Control Group ◽  
Akt Signaling Pathway ◽  
Wide Range

Background: Berberine, a well-known component of the Chinese herbal medicine Huanglian, has wide range of biochemical and pharmacological effects, including antineoplastic effect, but the exact mechanisms remain unclear. The aim of the present study was to evaluate the potential chemo-sensitization effect of berberine in ovarian cancer cell line A2780. Methods: The expression of miR-93 was measure by RT-PCR. The target of miR-93 was confirmed by luciferase activity assay. Hoechst 33258 staining, Annexin V and PI double staining were used for apoptosis analysis. Results: In this study, we found A2780/DDP cells that were incubated with berberine combined with cisplatin had a significantly lower survival than the control group. Berberine enhanced cisplatin induced apoptosis and induced G0/G1 cell cycle arrest in A2780 cells. Next, we observed that the miR-93 levels in cisplatin resistant cell lines were higher than that in cisplatin sensitive cell lines. Furthermore, our study found berberine could inhibit miR-93 expression and function in ovarian cancer, as shown by an increase of its target PTEN, an important tumor suppressor in ovarian cancer. A2780 cells that were treated with PTEN siRNA had increased survival compared to NC group and this could be partly alleviated by the AKT inhibitor Triciribine. More importantly, A2780 cells that were treated with PTEN siRNA had a survival pattern that is similar to cells with miR-93 overexpression. Conclusion: The results suggested that berberine modulated the sensitivity of cisplatin through miR-93/PTEN/AKT signaling pathway in the ovarian cancer cells.

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