scholarly journals Proteomic Profile of Carbonylated Proteins Screen Regulation of Apoptosis via CaMK Signaling in Response to Regular Aerobic Exercise

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Wenfeng Liu ◽  
Li Li ◽  
Heyu Kuang ◽  
Yan Xia ◽  
Zhiyuan Wang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Aerobic Exercise ◽  
Protein Kinase B ◽  
Mammalian Target Of Rapamycin ◽  
Rat Striatum ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Calcium Calmodulin Dependent ◽  
Dependent Protein ◽  
Phosphoinositide 3 Kinase

To research carbonylated proteins and screen molecular targets in the rat striatum on regular aerobic exercise, male Sprague-Dawley rats (13 months old, n = 24) were randomly divided into middle-aged sedentary control (M-SED) and aerobic exercise (M-EX) groups (n = 12 each). Maximum oxygen consumption (VO2max) gradually increased from 50%–55% to 65%–70% for a total of 10 weeks. A total of 36 carbonylated proteins with modified oxidative sites were identified by Electrospray Ionization-Quadrupole-Time of Flight-Mass Spectrometer (ESI-Q-TOF-MS), including 17 carbonylated proteins unique to the M-SED group, calcium/calmodulin-dependent protein kinase type II subunit beta (CaMKIIβ), and heterogeneous nuclear ribonucleoprotein A2/B1 (Hnrnpa2b1), among others, and 19 specific to the M-EX group, ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1), and malic enzyme, among others. Regular aerobic exercise improved behavioral and stereological indicators, promoted normal apoptosis (P < 0.01), alleviated carbonylation of the CaMKIIβ and Hnrnpa2b1, but induced carbonylation of the UCH-L1, and significantly upregulated the expression levels of CaMKIIβ, CaMKIIα, and Vdac1 (p < 0.01) and Hnrnpa2b1 and UCH-L1 (p < 0.01), as well as the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways (PI3K/Akt/mTOR) pathway-related genes Akt and mTOR. Regular aerobic exercise for 10 weeks (incremental for the first 6 weeks followed by constant loading for 4 weeks) enhanced carbonylation of CaMKIIβ, Hnrnpa2b1, and modulated apoptosis via activation of CaMK and phosphoinositide 3-kinase/protein kinase B/mTOR signaling. It also promoted normal apoptosis in the rat striatum, which may have protective effects in neurons.

Lupeol Inhibits Proliferation and Promotes Apoptosis of Ovarian Cancer Cells by Inactivating Phosphoinositide-3-Kinase/Protein Kinase B/ Mammalian Target of Rapamycin Pathway

2020 ◽  
Vol 19 (2) ◽  
pp. 206-210
Author(s):  
Feng Chen ◽  
Bei Zhang
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Protein Kinase ◽  
Cell Viability ◽  
Cancer Cells ◽  
Protein Kinase B ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Ovarian Cancer Cells ◽  
Phosphoinositide 3 Kinase

Lupeol exhibits multiple pharmacological activities including, anticancerous, anti-inflammatory, and antioxidant. The aim of this study was to explore the anticancerous activity of lupeol on ovarian cancer cells and examine its mechanism of action. To this end, increasing concentrations of lupeol on cell viability, cell cycle, and apoptosis in Caov-3 cells were evaluated. Lupeol inhibited cell viability, induced G1 phase arrest in cell cycle, increased cell apoptosis, and inhibited the ratio of phospho-Akt/protein kinase B and phospho-mammalian target of rapamycin/mammalian target of rapamycin. In conclusion, these data suggest that lupeol may play a therapeutic role in ovarian cancer.

scholarly journals Domain Swapping Used To Investigate the Mechanism of Protein Kinase B Regulation by 3-Phosphoinositide-Dependent Protein Kinase 1 and Ser473 Kinase

1999 ◽  
Vol 19 (7) ◽  
pp. 5061-5072 ◽  
Author(s):  
Mirjana Andjelković ◽  
Sauveur-Michel Maira ◽  
Peter Cron ◽  
Peter J. Parker ◽  
Brian A. Hemmings
Keyword(s):  
Protein Kinase ◽  
Kinase Inhibitors ◽  
Protein Kinase B ◽  
Second Messengers ◽  
Activation Mechanism ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Phosphoinositide 3 Kinase ◽  
Regulatory Sites

ABSTRACT Protein kinase B (PKB or Akt), a downstream effector of phosphoinositide 3-kinase (PI 3-kinase), has been implicated in insulin signaling and cell survival. PKB is regulated by phosphorylation on Thr308 by 3-phosphoinositide-dependent protein kinase 1 (PDK1) and on Ser473 by an unidentified kinase. We have used chimeric molecules of PKB to define different steps in the activation mechanism. A chimera which allows inducible membrane translocation by lipid second messengers that activate in vivo protein kinase C and not PKB was created. Following membrane attachment, the PKB fusion protein was rapidly activated and phosphorylated at the two key regulatory sites, Ser473 and Thr308, in the absence of further cell stimulation. This finding indicated that both PDK1 and the Ser473 kinase may be localized at the membrane of unstimulated cells, which was confirmed for PDK1 by immunofluorescence studies. Significantly, PI 3-kinase inhibitors prevent the phosphorylation of both regulatory sites of the membrane-targeted PKB chimera. Furthermore, we show that PKB activated at the membrane was rapidly dephosphorylated following inhibition of PI 3-kinase, with Ser473 being a better substrate for protein phosphatase. Overall, the results demonstrate that PKB is stringently regulated by signaling pathways that control both phosphorylation/activation and dephosphorylation/inactivation of this pivotal protein kinase.

Expression of calcium/calmodulin-dependent protein kinase II in dorsal root ganglia in diabetic rats 6 months and 1 year after diabetes induction

2013 ◽  
Vol 4 (4) ◽  
pp. 259-259
Author(s):  
L. Ferhatovic ◽  
A. Jelicic ◽  
M. Boric ◽  
A. Banozic ◽  
D. Sapunar ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Dorsal Root ◽  
Control Group ◽  
Type I ◽  
Sprague Dawley ◽  
Dependent Protein Kinase ◽  
Calcium Calmodulin Dependent ◽  
Protein Kinase Ii ◽  
Dependent Protein ◽  
Diabetes Induction

Abstract Aim The aim of this study was to compare expression of total calcium/calmodulin-dependent protein kinase II (tCaMKII) and its α, β, γ and δ isoforms in dorsal root ganglion (DRG) in rat models of diabetes mellitus type I (DM1), 6 months and 1 year after diabetes induction. Methods A total of 45 male Sprague-Dawley rats weighing 160-200 g were assigned into four experimental groups: 6-months DM1 and its control group, 1-year and its control group. For the induction of DM1, after overnight fasting animals were injected intraperitonealy with 55 mg/kg of the streptozotocine (STZ). Rats were sacrificed 6 months and 1 year after the diabetes induction. The L4 and L5 ganglions were removed, fixed, embedded in freezing medium and sectioned on a cryostat. Immunofluorescence analysis was performed for detection of tCaMKII and its α, β, γ and δ isoforms. Image J software was used for analysis of immunofluorescence. Results The diabetes was successfully induced as confirmed by measurement of glucose levels and weight increase. Analysis of tCaMKII expression in DRGs revealed no differences between DM1 and control animals after 6 and 12 months. In diabetic animals, the expression of α and β isoforms decreased significantly after 6 months, compared to the controls, while decrease of γ and δ was observed after one year of diabetes in diabetic animals. Conclusions The observed changes in the expression of CaMKII isoforms reveal plastic changes of this enzyme during the chronic diabetic state and may be involved in the chronic neuropathic pain development.

scholarly journals MicroRNA Expression Profiling Screen miR-3557/324-Targeted CaMK/mTOR in the Rat Striatum of Parkinson’s Disease in Regular Aerobic Exercise

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Wenfeng Liu ◽  
Li Li ◽  
Shaopeng Liu ◽  
Zhiyuan Wang ◽  
Heyu Kuang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Aerobic Exercise ◽  
Mammalian Target Of Rapamycin ◽  
Rat Striatum ◽  
Voltage Dependent ◽  
Selective Channel ◽  
Dependent Protein ◽  
6 Hydroxydopamine ◽  
Carboxy Terminal

This study aimed to screen the target miRNAs and to investigate the differential miR-3557/324-targeted signal mechanisms in the rats’ model of Parkinson’s disease (PD) with regular aerobic exercise. Rats were divided into sedentary control PD group (SED-PD, n = 18) and aerobic exercise PD group (EX-PD, n = 22). After 8 weeks of regular aerobic exercise, a 6-hydroxydopamine- (6-OHDA-) induced PD lesion model was constructed. Preregular aerobic exercises enhanced the injury resistance of rats with 6-OHDA-induced PD. The rotational behavior after injection of apomorphine hydrochloride was alleviated. Under the scanning electron microscopy, we found the neurons, axons, and villi of the striatum were clearly and tightly arranged, and neurons and axons significantly becoming larger. Tyrosine hydroxylase (TH) was increased significantly and α-synuclein protein expression was reduced in the EX-PD group compared to the SED-PD group. Screening from miRNA microarray chip, we further found upregulation of miR-3557 and downregulation of miR-324 were closely related to the calcium-modulating signaling pathway, remitting the progress of Parkinson’s disease on aerobic exercise. Compared to the SED-PD group, Ca2+/calmodulin dependent protein kinase II (CaMK2α) was upregulated, but CaMKV and voltage-dependent anion-selective channel protein 1 (Vdac1) were significantly downregulated in the EX-PD group. Additionally, phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) expression were activated, and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) expression was upregulated in the EX-PD group. Conclusions: the adaptive mechanism of regular aerobic exercise delaying neurodegenerative diseases and lesions was that miR-3557/324 was activated to regulate one of its targets CaMKs signaling pathways. CaMKs, coordinated with mTOR pathway-related gene expression, improved UCH-L1 level to favor for delaying neurodegeneration or improving the pathogenesis of PD lesions.

Lupeol induces autophagy and apoptosis with reduced cancer stem-like properties in retinoblastoma via phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin inhibition

2021 ◽  
Author(s):  
Songtian Che ◽  
Shuai Wu ◽  
Peng Yu
Keyword(s):  
Protein Kinase ◽  
Cell Lines ◽  
Protein Kinase B ◽  
Mammalian Target Of Rapamycin ◽  
Inhibitory Effect ◽  
Target Of Rapamycin ◽  
Anticancer Effects ◽  
Retinoblastoma Cells ◽  
Phosphoinositide 3 Kinase

Abstract Objectives To evaluate the anticancer effects of lupeol in retinoblastoma cells. Methods WERI-Rb-1 and Y-79 cell lines were used to evaluate the anticancer effect of lupeol. After lupeol treatment, the viability, proliferation, apoptosis, cancer stem-like properties, autophagy and in vivo tumour xenograft formation were detected. Key findings In this study, lupeol decreased cell viability in both WERI-Rb-1 and Y-79 cell lines. Lupeol could also inhibit proliferation and induce apoptosis of RB cells, with increased Bax level and decreased Ki67, survivin and Bcl-2 levels. Furthermore, lupeol could suppress the spheroid formation and stem-like properties of RB cells. Moreover, LC3 II/LC3 I ratio and the levels of Beclin1 and ATG7 were increased after lupeol treatment, indicating that lupeol could induce autophagy in RB cells. Next, the inhibitory effect of lupeol on the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway was observed. In tumour-bearing mice, lupeol suppressed tumour growth, and this might relate to its role in cell apoptosis, autophagy and stem-like properties. Conclusions Lupeol suppressed proliferation and cancer stem-like properties, and promoted autophagy and apoptosis of RB cells by restraining the PI3K/AKT/mTOR pathway.

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