Protein tyrosine phosphatase alpha regulates cell detachment and cell death profiles induced by nitric oxide donors in the A431 human carcinoma cell line

Costa, P.; Batista, Wagner L.; Curcio, Marli F.; Moraes, Miriam S.; Borges, Roberta Eller; Nascimento, P.A.; Travassos, Luiz R.; Monteiro, Hugo P.

doi:10.1179/174329211x12968219310792

Cited by 9 publications

(6 citation statements)

References 34 publications

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“…NO plays a crucial role in the signal transduction pathway involved in cell proliferation, survival, and cell death in almost all types of cells 51,52 . Additionally, NO is a well-known critical factor involved in inflammatory responses in many types of cells, including macrophages 53,54 .…”

Section: Discussionmentioning

confidence: 99%

Lactobacillus paracasei-derived extracellular vesicles attenuate the intestinal inflammatory response by augmenting the endoplasmic reticulum stress pathway

Choi

Moon

Shin³

et al. 2020

Exp Mol Med

124

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Lactobacillus paracasei is a major probiotic and is well known for its anti-inflammatory properties. Thus, we investigated the effects of L. paracasei-derived extracellular vesicles (LpEVs) on LPS-induced inflammation in HT29 human colorectal cancer cells and dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice. ER stress inhibitors (salubrinal or 4-PBA) or CHOP siRNA were utilized to investigate the relationship between LpEV-induced endoplasmic reticulum (ER) stress and the inhibitory effect of LpEVs against LPS-induced inflammation. DSS (2%) was administered to male C57BL/6 mice to induce inflammatory bowel disease, and disease activity was measured by determining colon length, disease activity index, and survival ratio. In in vitro experiments, LpEVs reduced the expression of the LPSinduced pro-inflammatory cytokines IL-1α, IL-1β, IL-2, and TNFα and increased the expression of the anti-inflammatory cytokines IL-10 and TGFβ. LpEVs reduced LPS-induced inflammation in HT29 cells and decreased the activation of inflammation-associated proteins, such as COX-2, iNOS and NFκB, as well as nitric oxide. In in vivo mouse experiments, the oral administration of LpEVs also protected against DSS-induced colitis by reducing weight loss, maintaining colon length, and decreasing the disease activity index (DAI). In addition, LpEVs induced the expression of endoplasmic reticulum (ER) stress-associated proteins, while the inhibition of these proteins blocked the anti-inflammatory effects of LpEVs in LPS-treated HT29 cells, restoring the pro-inflammatory effects of LPS. This study found that LpEVs attenuate LPS-induced inflammation in the intestine through ER stress activation. Our results suggest that LpEVs have a significant effect in maintaining colorectal homeostasis in inflammation-mediated pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Lactobacillus paracasei-derived extracellular vesicles attenuate the intestinal inflammatory response by augmenting the endoplasmic reticulum stress pathway

Choi

Moon

Shin³

et al. 2020

Exp Mol Med

124

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“…Ectopic expression of RPTPa in these cells was shown to switch the mechanism of cell death from apoptosis to necrosis (19). The same group reported that another NO donor, SNAP, stimulated cell proliferation in fibroblasts expressing RPTPa while promoting growth arrest in cells with deleted RPTPa gene (18).…”

Section: No-induced and Rptpa-mediated Cell Deathmentioning

confidence: 86%

Reactive Nitrogen Species and Hydrogen Sulfide as Regulators of Protein Tyrosine Phosphatase Activity

Heneberg

2014

Antioxidants & Redox Signaling

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Significance: Redox modifications of thiols serve as a molecular code enabling precise and complex regulation of protein tyrosine phosphatases (PTPs) and other proteins. Particular gasotransmitters and even the redox modifications themselves affect each other, of which a typical example is S-nitrosylation-mediated protection against the further oxidation of protein thiols. Recent Advances: For a long time, PTPs were considered constitutively active housekeeping enzymes. This view has changed substantially over the last two decades, and the PTP family is now recognized as a group of tightly and flexibly regulated fundamental enzymes. In addition to the conventional ways in which they are regulated, including noncovalent interactions, phosphorylation, and oxidation, the evidence that has accumulated during the past two decades suggests that many of these enzymes are also modulated by gasotransmitters, namely by nitric oxide (NO) and hydrogen sulfide (H 2 S). Critical Issues: The specificity and selectivity of the methods used to detect nitrosylation and sulfhydration remains to be corroborated, because several researchers raised the issue of false-positive results, particularly when using the most widespread biotin switch method. Further development of robust and straightforward proteomic methods is needed to further improve our knowledge of the full extent of the gasotransmitters-mediated changes in PTP activity, selectivity, and specificity. Further Directions: Results of the hitherto performed studies on gasotransmitter-mediated PTP signaling await translation into clinical medicine and pharmacotherapeutics. In addition to directly affecting the activity of particular PTPs, the use of reversible S-nitrosylation as a protective mechanism against oxidative stress should be of high interest. Antioxid. Redox Signal. 20, 2191-2209.

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“…[13,38] NO is not restricted to pro-tumor effects, since NO can also promote anti-tumor actions. [2,39,40] Nitrosative stress conditions resulting from an activated immune response or exposure to high concentrations of nitrosylating agents lead to cancer cell death. [7,39] Therefore, concentrations of NO, time of exposure, and cell sensitivity to the radical determine the NO-mediated course of action in tumor cells.…”

Section: Nitric Oxide and Cancer: A Two-way Streetmentioning

confidence: 99%

“…[2,39,40] Nitrosative stress conditions resulting from an activated immune response or exposure to high concentrations of nitrosylating agents lead to cancer cell death. [7,39] Therefore, concentrations of NO, time of exposure, and cell sensitivity to the radical determine the NO-mediated course of action in tumor cells. [13,41] Low to intermediate concentrations of NO/ RSNO stimulate oncogenic signaling pathways…”

Section: Nitric Oxide and Cancer: A Two-way Streetmentioning

confidence: 99%

“…Exposure of A431 cells over-expressing PTPa to SNP decreased the activation of caspase-8 and caspase-3 and induced cell death predominantly by necrosis. [39] Different concentrations of the RSNOs lead to different outcomes derived from upstream S-nitrosylation of Ras. [30,58,60] This is supported by findings on the induction of the apoptotic process in human acute monocytic leukemia cells (THP-1) through the activation of the Ras-ERK1/2 MAP kinases pathway by high/supra-physiological concentrations of GSNO.…”

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confidence: 99%

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Nitric oxide: Protein tyrosine phosphorylation and protein S-nitrosylation in cancer

et al. 2015

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N itric oxide (NO) is a free radical with signaling capacity that plays an important role in the cardiovascular, neuronal, and immune systems, among others. NO regulates a number of physiological processes through the activation of two major signaling pathways: The activation of the enzyme guanylyl cyclase to form cGMP and S-nitrosylation, a covalent attachment of an NO moiety to a reactive cysteine residue in peptides and proteins. NO produced by the endothelial isoform of NO synthase (eNOS) regulates blood pressure. NO produced in neurons by the neuronal NOS isoform (nNOS) functions as a neurotransmitter. The constitutively expressed isoforms eNOS and nNOS release low fluxes of NO that are associated with cell protection and proliferation. Inflammatory cytokines and toxins induce the inducible NOS isoform (iNOS) in macrophages. Production of NO under these conditions is much higher compared to its production by constitutive enzymes. [1] Higher NO fluxes such as those produced by iNOS stimulated by inflammatory cytokines in macrophages or generated by millimolar concentrations of NO donors are cytotoxic and promote apoptosis. [2] The constitutive NOS isoforms have been detected in some malignant tumors. Activation of eNOS is involved in the initiation and maintenance of tumor growth in pancreatic cancer cell lines.[3] Tumor progression in prostate cancer is associated with eNOS expression, while malignant melanoma progression is associated with nNOS expression. [4,5] The iNOS isoform is ubiquitously distributed in malignant tumors, but its role in tumor development is highly complex and poorly understood.[6] The expression levels of iNOS and Special EditionCancer is a worldwide health problem leading to a high incidence of morbidity and mortality. Malignant transformation can occur by expression of oncogenes, over-expression and deregulated activation of proto-oncogenes, and inactivation of tumor suppressor genes. These cellular actions occur through stimulation of oncogenic signaling pathways. Nitric oxide (NO) can induce genetic changes in cells and its intracellular generation can lead to tumor formation and progression. It can also promote anti-tumor activities. The pro-and anti-tumor activities of NO are dependent on its intracellular concentration, cell compartmentalization, and cell sensitivity. NO affects a number of oncogenic signaling pathways. This review focuses on two oncogenic signaling pathways: NO-EGFR-Src-FAK and NO-Ras-EGFR-ERK1/2 MAP kinases. In these pathways, low to intermediate concentrations of NO/S-nitrosothiols (RSNOs) stimulate oncogenic signaling, while high concentrations of NO/RSNO stimulate anti-oncogenic signaling. Increasing knowledge on pro-and anti-tumorigenic activities of NO and related reactive species such as RSNOs has fostered the research and synthesis of novel NO-based chemotherapeutic agents. RSNOs, effective as NO donors and trans-nitrosylating agents under appropriate conditions, may operate as potential chemotherapeutic agents. (Biomed J 2015;38:380-388) associat...

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Protein tyrosine phosphatase alpha regulates cell detachment and cell death profiles induced by nitric oxide donors in the A431 human carcinoma cell line

Cited by 9 publications

References 34 publications

Lactobacillus paracasei-derived extracellular vesicles attenuate the intestinal inflammatory response by augmenting the endoplasmic reticulum stress pathway

Lactobacillus paracasei-derived extracellular vesicles attenuate the intestinal inflammatory response by augmenting the endoplasmic reticulum stress pathway

Reactive Nitrogen Species and Hydrogen Sulfide as Regulators of Protein Tyrosine Phosphatase Activity

Nitric oxide: Protein tyrosine phosphorylation and protein S-nitrosylation in cancer

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