Calcium Signaling Involvement in Cadmium-Induced Astrocyte Cytotoxicity and Cell Death Through Activation of MAPK and PI3K/Akt Signaling Pathways

2015 ◽  
Vol 40 (9) ◽  
pp. 1929-1944 ◽  
Author(s):  
Jiao Hua Jiang ◽  
Guo Ge ◽  
Kai Gao ◽  
Ying Pang ◽  
Rui Chao Chai ◽  
...  
Keyword(s):  
Cell Death ◽  
Calcium Signaling ◽  
Signaling Pathways ◽  
Akt Signaling

scholarly journals Ozone-Induced Cell Death Mediated with Oxidative and Calcium Signaling Pathways in Tobacco Bel-W3 and Bel-B Cell Suspension Cultures

2006 ◽  
Vol 1 (6) ◽  
pp. 312-322 ◽  
Author(s):  
Takashi Kadono ◽  
Yuka Yamaguchi ◽  
Takuya Furuichi ◽  
Manabu Hirono ◽  
Jean-Pierre Garrec ◽  
...  
Keyword(s):  
Cell Death ◽  
Calcium Signaling ◽  
B Cell ◽  
Cell Suspension ◽  
Signaling Pathways ◽  
Cell Suspension Cultures ◽  
Suspension Cultures

scholarly journals Quercetin Induces Apoptosis via Downregulation of Vascular Endothelial Growth Factor/Akt Signaling Pathway in Acute Myeloid Leukemia Cells

2020 ◽  
Vol 11 ◽  
Author(s):  
Huan Shi ◽  
Xin-Yu Li ◽  
Yao Chen ◽  
Xing Zhang ◽  
Yong Wu ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Myeloid Leukemia ◽  
Signaling Pathways ◽  
Myeloid Leukemia ◽  
Akt Signaling ◽  
Convincing Evidence ◽  
Chemical Proteomics ◽  
Mitochondria Membrane Potential ◽  
Acute Myeloid Leukemia Cells ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is an aggressive haematological malignancy characterized by highly proliferative accumulation of immature and dysfunctional myeloid cells. Quercetin (Qu), one kind of flavonoid, exhibits anti-cancer property in multiple types of solid tumor, but its effect on acute myeloid leukemia is less studied, and the underlying mechanisms still largely unknown. This study aimed to explore the specific target and potential mechanism of quercetin-induced cell death in AML. First, we found that quercetin induces cell death in the form of apoptosis, which was caspase dependent. Second, we found that quercetin-induced apoptosis depends on the decrease of mitochondria membrane potential (MMP) and Bcl-2 proteins. With quantitative chemical proteomics, we observed the downregulation of VEGFR2 and PI3K/Akt signaling in quercetin-treated cells. Consistently, cell studies also identified that VEGFR2 and PI3K/Akt signaling pathways are involved in the action of quercetin on mitochondria and Bcl-2 proteins. The decrease of MMP and cell death could be rescued when PI3K/Akt signaling is activated, suggesting that VEGFR2 and PI3K/Akt exert as upstream regulators for quercetin effect on apoptosis induction in AML cells. In conclusion, our findings from this study provide convincing evidence that quercetin induces cell death via downregulation of VEGF/Akt signaling pathways and mitochondria-mediated apoptosis in AML cells.

scholarly journals aPC/PAR1 confers endothelial anti-apoptotic activity via a discrete, β-arrestin-2–mediated SphK1-S1PR1-Akt signaling axis

2021 ◽  
Vol 118 (49) ◽  
pp. e2106623118
Author(s):  
Olivia Molinar-Inglis ◽  
Cierra A. Birch ◽  
Dequina Nicholas ◽  
Lennis Orduña-Castillo ◽  
Metztli Cisneros-Aguirre ◽  
...  
Keyword(s):  
Cell Death ◽  
Endothelial Dysfunction ◽  
Signaling Pathways ◽  
Activated Protein C ◽  
Akt Signaling ◽  
Endothelial Barrier ◽  
Structural Protein ◽  
Signaling Axis ◽  
Sphingosine 1 Phosphate ◽  
Apoptotic Activity

Endothelial dysfunction is associated with vascular disease and results in disruption of endothelial barrier function and increased sensitivity to apoptosis. Currently, there are limited treatments for improving endothelial dysfunction. Activated protein C (aPC), a promising therapeutic, signals via protease-activated receptor-1 (PAR1) and mediates several cytoprotective responses, including endothelial barrier stabilization and anti-apoptotic responses. We showed that aPC-activated PAR1 signals preferentially via β-arrestin-2 (β-arr2) and dishevelled-2 (Dvl2) scaffolds rather than G proteins to promote Rac1 activation and barrier protection. However, the signaling pathways utilized by aPC/PAR1 to mediate anti-apoptotic activities are not known. aPC/PAR1 cytoprotective responses also require coreceptors; however, it is not clear how coreceptors impact different aPC/PAR1 signaling pathways to drive distinct cytoprotective responses. Here, we define a β-arr2–mediated sphingosine kinase-1 (SphK1)-sphingosine-1-phosphate receptor-1 (S1PR1)-Akt signaling axis that confers aPC/PAR1-mediated protection against cell death. Using human cultured endothelial cells, we found that endogenous PAR1 and S1PR1 coexist in caveolin-1 (Cav1)–rich microdomains and that S1PR1 coassociation with Cav1 is increased by aPC activation of PAR1. Our study further shows that aPC stimulates β-arr2–dependent SphK1 activation independent of Dvl2 and is required for transactivation of S1PR1-Akt signaling and protection against cell death. While aPC/PAR1-induced, extracellular signal–regulated kinase 1/2 (ERK1/2) activation is also dependent on β-arr2, neither SphK1 nor S1PR1 are integrated into the ERK1/2 pathway. Finally, aPC activation of PAR1-β-arr2–mediated protection against apoptosis is dependent on Cav1, the principal structural protein of endothelial caveolae. These studies reveal that different aPC/PAR1 cytoprotective responses are mediated by discrete, β-arr2–driven signaling pathways in caveolae.

Crude extract of Origanum vulgare L. induced cell death and suppressed MAPK and PI3/Akt signaling pathways in SW13 and H295R cell lines

2018 ◽  
Vol 33 (11) ◽  
pp. 1646-1649 ◽  
Author(s):  
Beatrice Rubin ◽  
Jacopo Manso ◽  
Halenya Monticelli ◽  
Loris Bertazza ◽  
Marco Redaelli ◽  
...  
Keyword(s):  
Cell Death ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Crude Extract ◽  
Akt Signaling ◽  
Origanum Vulgare

Sorafenib induces autophagic cell death and apoptosis in hepatic stellate cell through the JNK and Akt signaling pathways

2016 ◽  
Vol 27 (3) ◽  
pp. 192-203 ◽  
Author(s):  
Huiyao Hao ◽  
Di Zhang ◽  
Junli Shi ◽  
Yan Wang ◽  
Lei Chen ◽  
...  
Keyword(s):  
Cell Death ◽  
Signaling Pathways ◽  
Hepatic Stellate Cell ◽  
Stellate Cell ◽  
Akt Signaling ◽  
Autophagic Cell Death

Biological role of AKT, and regulation of AKT signaling pathway by thymoquinone: perspectives in cancer therapeutics

2020 ◽  
Vol 20 ◽  
Author(s):  
Md. Junaid ◽  
Yeasmin Akter ◽  
Syeda Samira Afrose ◽  
Mousumi Tania ◽  
Md. Asaduzzaman Khan
Keyword(s):  
Clinical Trials ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Inhibitory Effect ◽  
Akt Signaling ◽  
Review Article ◽  
Therapeutic Drug ◽  
Akt Signaling Pathway ◽  
Anti Cancer

Background: AKT/PKB is an important enzyme with numerous biological functions, and its overexpression is related to the carcinogenesis. AKT stimulates different signaling pathways that are downstream of activated tyrosine kinases and phosphatidylinositol 3-kinase, hence functions as an important target for anti-cancer drugs. Objective: In this review article, we have interpreted the role of AKT signaling pathways in cancer and natural inhibitory effect of Thymoquinone (TQ) in AKT and its possible mechanism. Method: We have collected the updated information and data on AKT, their role in cancer and inhibitory effect of TQ in AKT signaling pathway from google scholar, PubMed, Web of Science, Elsevier, Scopus and many more. Results: There are many drugs already developed, which can target AKT, but very few among them have passed clinical trials. TQ is a natural compound, mainly found in black cumin, which has been found to have potential anti-cancer activities. TQ targets numerous signaling pathways, including AKT, in different cancers. In fact, many studies revealed that AKT is one of the major targets of TQ. The preclinical success of TQ suggests its clinical studies on cancer. Conclusion: This review article summarizes the role of AKT in carcinogenesis, its potent inhibitors in clinical trials, and how TQ acts as an inhibitor of AKT and TQ’s future as a cancer therapeutic drug.

scholarly journals Analysis of the Oxidative Burst and Its Relevant Signaling Pathways in Leptosphaeria maculans—Brassica napus Pathosystem

2021 ◽  
Vol 22 (9) ◽  
pp. 4812
Author(s):  
Cunchun Yang ◽  
W. G. Dilantha Fernando
Keyword(s):  
Cell Death ◽  
Signaling Pathways ◽  
Oxidative Burst ◽  
Defense Mechanisms ◽  
Leptosphaeria Maculans ◽  
Gene Interaction ◽  
Early Response ◽  
Marker Genes ◽  
Ros Accumulation ◽  
Microbe Interactions

An oxidative burst is an early response of plants to various biotic/abiotic stresses. In plant-microbe interactions, the plant body can induce oxidative burst to activate various defense mechanisms to combat phytopathogens. A localized oxidative burst is also one of the typical behaviors during hypersensitive response (HR) caused by gene-for-gene interaction. In this study, the occurrence of oxidative burst and its signaling pathways was studied from different levels of disease severity (i.e., susceptible, intermediate, and resistant) in the B. napus–L. maculans pathosystem. Canola cotyledons with distinct levels of resistance exhibited differential regulation of the genes involved in reactive oxygen species (ROS) accumulation and responses. Histochemical assays were carried out to understand the patterns of H2O2 accumulation and cell death. Intermediate and resistant genotypes exhibited earlier accumulation of H2O2 and emergence of cell death around the inoculation origins. The observations also suggested that the cotyledons with stronger resistance were able to form a protective region of intensive oxidative bursts between the areas with and without hyphal intrusions to block further fungal advancement to the uninfected regions. The qPCR analysis suggested that different onset patterns of some marker genes in ROS accumulation/programmed cell death (PCD) such as RBOHD, MPK3 were associated with distinct levels of resistance from B. napus cultivars against L. maculans. The observations and datasets from this article indicated the distinct differences in ROS-related cellular behaviors and signaling between compatible and incompatible interactions.

scholarly journals Akt signaling is activated by TGFβ2 and impacts tenogenic induction of mesenchymal stem cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sophia K. Theodossiou ◽  
Jett B. Murray ◽  
LeeAnn A. Hold ◽  
Jeff M. Courtright ◽  
Anne M. Carper ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Akt Signaling ◽  
Cell Alignment ◽  
Limited Information ◽  
Akt Inhibitor ◽  
Tenogenic Differentiation

Abstract Background Tissue engineered and regenerative approaches for treating tendon injuries are challenged by the limited information on the cellular signaling pathways driving tenogenic differentiation of stem cells. Members of the transforming growth factor (TGF) β family, particularly TGFβ2, play a role in tenogenesis, which may proceed via Smad-mediated signaling. However, recent evidence suggests some aspects of tenogenesis may be independent of Smad signaling, and other pathways potentially involved in tenogenesis are understudied. Here, we examined the role of Akt/mTORC1/P70S6K signaling in early TGFβ2-induced tenogenesis of mesenchymal stem cells (MSCs) and evaluated TGFβ2-induced tenogenic differentiation when Smad3 is inhibited. Methods Mouse MSCs were treated with TGFβ2 to induce tenogenesis, and Akt or Smad3 signaling was chemically inhibited using the Akt inhibitor, MK-2206, or the Smad3 inhibitor, SIS3. Effects of TGFβ2 alone and in combination with these inhibitors on the activation of Akt signaling and its downstream targets mTOR and P70S6K were quantified using western blot analysis, and cell morphology was assessed using confocal microscopy. Levels of the tendon marker protein, tenomodulin, were also assessed. Results TGFβ2 alone activated Akt signaling during early tenogenic induction. Chemically inhibiting Akt prevented increases in tenomodulin and attenuated tenogenic morphology of the MSCs in response to TGFβ2. Chemically inhibiting Smad3 did not prevent tenogenesis, but appeared to accelerate it. MSCs treated with both TGFβ2 and SIS3 produced significantly higher levels of tenomodulin at 7 days and morphology appeared tenogenic, with localized cell alignment and elongation. Finally, inhibiting Smad3 did not appear to impact Akt signaling, suggesting that Akt may allow TGFβ2-induced tenogenesis to proceed during disruption of Smad3 signaling. Conclusions These findings show that Akt signaling plays a role in TGFβ2-induced tenogenesis and that tenogenesis of MSCs can be initiated by TGFβ2 during disruption of Smad3 signaling. These findings provide new insights into the signaling pathways that regulate tenogenic induction in stem cells.

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