cAMP antagonizes ERK-dependent antiapoptotic action of insulin

Cui, Zhi; Hong, Na Young; Guan, Jian; Kang, Hee Kyoung; Lee, Dong Hoon; Lee, Young Ki; Park, Deok Bae

doi:10.5483/bmbrep.2011.44.3.205

Cited by 6 publications

(5 citation statements)

References 33 publications

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“…The DNA content in each cell nucleus was determined with a FACSCalibur flow cytometer (Becton-Dickinson, San Jose, CA, USA). 6 …”

Section: Methodsmentioning

confidence: 99%

Polyphenols Isolated from Allium cepa L. Induces Apoptosis by Induction of p53 and Suppression of Bcl-2 through Inhibiting PI3K/Akt Signaling Pathway in AGS Human Cancer Cells

Lee¹,

Yi²,

Yun³

et al. 2014

J Cancer Prev

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Background: The extract of Allium cepa Linn is commonly used as adjuvant food for cancer therapy. We assumed that it includes a potential source of anti-cancer properties.Methods: We investigated anti-cancer effects of polyphenols extracted from lyophilized A. cepa Linn (PEAL) in AGS human cancer cells.Results: PEAL inhibited cell growth in a dose-dependent manner. It was related to caspase-dependent apoptosis. We confirmed this finding with annexin V staining. PEAL up-regulated p53 expression, and subsequent Bax induction, down regulated Bcl-2 protein, anti-apoptotic protein. In addition, PEAL suppressed Akt activity and PEAL-induced apoptosis were significantly accentuated with Akt inhibitor (LY294002). Conclusions: Our data suggested that PEAL induce caspase-dependent apoptosis through mitochondrial pathway by up-regulating p53 protein, and subsequent Bax protein as well as by modulating Bcl-2 protein, and that PEAL induces caspase-dependent apoptosis at least in part through the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. This study provides evidence that PEAL might be useful for the treatment of cancer. ( In this study, we investigated the mechanisms of anticancer effects of PEAL on human AGS cells. MATERIALS AND METHODS Preparation of PEALPEAL isolated from the plants of A. cepa Linn which we bought from the market and 100 mg/mL concentration content was measured by propidium iodide (PI) staining.

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“…The DNA content in each cell nucleus was determined with a FACSCalibur flow cytometer (Becton-Dickinson, San Jose, CA, USA). 6 …”

Section: Methodsmentioning

confidence: 99%

Polyphenols Isolated from Allium cepa L. Induces Apoptosis by Induction of p53 and Suppression of Bcl-2 through Inhibiting PI3K/Akt Signaling Pathway in AGS Human Cancer Cells

Lee¹,

Yi²,

Yun³

et al. 2014

J Cancer Prev

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“…4A) (32). cAMP inhibits ERK signaling in various cell types (33)(34)(35). To investigate whether lactate-induced ERK phosphorylation is mediated by suppression of cAMP formation, we treated ECs with cAMP-elevating agent, forskolin, before lactate stimulation.…”

Section: Lactate-induced Erk1/2 Phosphorylation Is Mediated By Camp/r...mentioning

confidence: 99%

Lactate induces vascular permeability via disruption of VE-cadherin in endothelial cells during sepsis

et al. 2022

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Circulating lactate levels are a critical biomarker for sepsis and are positively correlated with sepsis-associated mortality. We investigated whether lactate plays a biological role in causing endothelial barrier dysfunction in sepsis. We showed that lactate causes vascular permeability and worsens organ dysfunction in CLP sepsis. Mechanistically, lactate induces ERK-dependent activation of calpain1/2 for VE-cadherin proteolytic cleavage, leading to the enhanced endocytosis of VE-cadherin in endothelial cells. In addition, we found that ERK2 interacts with VE-cadherin and stabilizes VE-cadherin complex in resting endothelial cells. Lactate-induced ERK2 phosphorylation promotes ERK2 disassociation from VE-cadherin. In vivo suppression of lactate production or genetic depletion of lactate receptor GPR81 mitigates vascular permeability and multiple organ injury and improves survival outcome in polymicrobial sepsis. Our study reveals that metabolic cross-talk between glycolysis-derived lactate and the endothelium plays a critical role in the pathophysiology of sepsis.

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“…The DNA content in each cell nucleus was determined with a FACSCalibur flow cytometer (Becton-Dickinson, San Jose, CA, U.S.A.). Two independent experiments were performed [ 11 ].…”

Section: Methodsmentioning

confidence: 99%

Tetraarsenic Hexoxide Induces Beclin-1-Induced Autophagic Cell Death as well as Caspase-Dependent Apoptosis in U937 Human Leukemic Cells

Han

Lee

Lü

et al. 2012

Evidence-Based Complementary and Alternative Medicine

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Tetraarsenic hexaoxide (As4O6) has been used in Korean folk remedy for the treatment of cancer since the late 1980s, and arsenic trioxide (As2O3) is currently used as a chemotherapeutic agent. However, evidence suggests that As4O6-induced cell death pathway was different from that of As2O3. Besides, the anticancer effects and mechanisms of As4O6 are not fully understood. Therefore, we investigated the anticancer activities of As4O6 on apoptosis and autophagy in U937 human leukemic cells. The growth of U937 cells was inhibited by As4O6 treatment in a dose- and a time-dependent manner, and IC50 for As4O6 was less than 2 μM. As4O6 induced caspase-dependent apoptosis and Beclin-1-induced autophagy, both of which were significantly attenuated by Bcl-2 augmentation and N-acetylcysteine (NAC) treatment. This study suggests that As4O6 should induce Beclin-1-induced autophagic cell death as well as caspase-dependent apoptosis and that it might be a promising agent for the treatment of leukemia.

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cAMP antagonizes ERK-dependent antiapoptotic action of insulin

Cited by 6 publications

References 33 publications

Polyphenols Isolated from Allium cepa L. Induces Apoptosis by Induction of p53 and Suppression of Bcl-2 through Inhibiting PI3K/Akt Signaling Pathway in AGS Human Cancer Cells

Polyphenols Isolated from Allium cepa L. Induces Apoptosis by Induction of p53 and Suppression of Bcl-2 through Inhibiting PI3K/Akt Signaling Pathway in AGS Human Cancer Cells

Lactate induces vascular permeability via disruption of VE-cadherin in endothelial cells during sepsis

Tetraarsenic Hexoxide Induces Beclin-1-Induced Autophagic Cell Death as well as Caspase-Dependent Apoptosis in U937 Human Leukemic Cells

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