Phenyl Saligenin Phosphate Induced Caspase-3 and c-Jun N-Terminal Kinase Activation in Cardiomyocyte-Like Cells

Felemban, Shatha Ghazi; Garner, A. Christopher; Smida, FA; Boocock, David J.; Hargreaves, Alan J.; Dickenson, John M.

doi:10.1021/acs.chemrestox.5b00338

Cited by 5 publications

(28 citation statements)

References 42 publications

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“…All activity was blocked by co-treatment with 100 μM ZDON. To determine whether this reflected covalent adduct formation between TG2 and PSP, recombinant TG2 was incubated with a dansylamine-labelled analogue of PSP, which had previously been used to identify PSP adducts in cardiomyocyte-like cells (Felamban et al 2015 ). The gel images in Fig.…”

Section: Resultsmentioning

confidence: 99%

Neurite outgrowth inhibitory levels of organophosphates induce tissue transglutaminase activity in differentiating N2a cells: evidence for covalent adduct formation

et al. 2020

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Organophosphate compounds (OPs) induce both acute and delayed neurotoxic effects, the latter of which is believed to involve their interaction with proteins other than acetylcholinesterase. However, few OP-binding proteins have been identified that may have a direct role in OP-induced delayed neurotoxicity. Given their ability to disrupt Ca2+ homeostasis, a key aim of the current work was to investigate the effects of sub-lethal neurite outgrowth inhibitory levels of OPs on the Ca2+-dependent enzyme tissue transglutaminase (TG2). At 1–10 µM, the OPs phenyl saligenin phosphate (PSP) and chlorpyrifos oxon (CPO) had no effect cell viability but induced concentration-dependent decreases in neurite outgrowth in differentiating N2a neuroblastoma cells. The activity of TG2 increased in cell lysates of differentiating cells exposed for 24 h to PSP and chlorpyrifos oxon CPO (10 µM), as determined by biotin-cadaverine incorporation assays. Exposure to both OPs (3 and/or 10 µM) also enhanced in situ incorporation of the membrane permeable substrate biotin-X-cadaverine, as indicated by Western blot analysis of treated cell lysates probed with ExtrAvidin peroxidase and fluorescence microscopy of cell monolayers incubated with FITC-streptavidin. Both OPs (10 µM) stimulated the activity of human and mouse recombinant TG2 and covalent labelling of TG2 with dansylamine-labelled PSP was demonstrated by fluorescence imaging following SDS-PAGE. A number of TG2 substrates were tentatively identified by mass spectrometry, including cytoskeletal proteins, chaperones and proteins involved protein synthesis and gene regulation. We propose that the elevated TG2 activity observed is due to the formation of a novel covalent adduct between TG2 and OPs.

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Section: Resultsmentioning

confidence: 99%

Neurite outgrowth inhibitory levels of organophosphates induce tissue transglutaminase activity in differentiating N2a cells: evidence for covalent adduct formation

et al. 2020

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“…( 51 , 52 ) Heat shock protein β-1 (also known as HSP-27) is a member of a small heat shock protein family and is involved in the regulation of apoptosis, protection of cells against oxidative stress. ( 53 ) Interestingly, it is reported that heat shock protein β-1 is able to prevent α-synuclein aggregation in the culture of neurons overexpressing α-synuclein and thus increases neuron survival. ( 54 ) Thus, the increase in expression levels of inorganic pyrophosphatase and heat shock protein β-1 may play a neuroprotective role in the DG after ischemia.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of the monkey hippocampus for elucidating ischemic resistance

Mori

Oikawa

Kurimoto

et al. 2020

J. Clin. Biochem. Nutr.

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It is well-known that the cornu Ammonis 1 (CA1) sector of hippocampus is vulnerable for the ischemic insult, whereas the dentate gyrus (DG) is resistant. Here, to elucidate its underlying mechanism, alternations of protein oxidation and expression of DG in the monkey hippocampus after ischemia-reperfusion by the proteomic analysis were studied by comparing CA1 data. Oxidative damage to proteins such as protein carbonylation interrupt the protein function. Carbonyl modification of molecular chaperone, heat shock 70 kDa protein 1 (Hsp70.1) was increased remarkably in CA1, but slightly in DG. In addition, expression levels of nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase sirtuin-2 (SIRT2) was significantly increased in DG after ischemia, but decreased in CA1. Accordingly, it is likely that SIRT2 upregulation and negligible changes of carbonylation of Hsp70.1 exert its neuroprotective effect in DG. On the contrary, carbonylation level of dihydropyrimidinase related protein 2 (DRP-2) and l -lactate dehydrogenase B chain (LDHB) were slightly increased in CA1 as shown previously, but remarkably increased in DG after ischemia. It is considered that DRP-2 and LDHB are specific targets of oxidative stress by ischemia insult and high carbonylation levels of DRP-2 may play an important role in modulating ischemic neuronal death.

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“…It has been reported that cardiomyocyte survival and death are regulated by extracellular ligands, cytokines, and growth factors that bind to cell surface receptors and induce intracellular specific signal transduction pathways [51]. Cardiac dysfunction usually occurs as a consequence of inflammatory, oxidative stress, and apoptosis mechanisms mediated by MAPK signaling pathways, and ERK, JNK, and p38-MAPK activation has been demonstrated in heart failure models [51]. Furthermore, the effects of DZN, phenyl-saligenin-phosphate (PSP), and CPF and their toxic metabolites (diazoxone and CPF-oxone) on H9c2 cardiomyoblasts were investigated.…”

Section: Organophosphorus Compound-induced Cardiovascular Diseases Armentioning

confidence: 99%

“…Furthermore, the effects of DZN, phenyl-saligenin-phosphate (PSP), and CPF and their toxic metabolites (diazoxone and CPF-oxone) on H9c2 cardiomyoblasts were investigated. Forty-eight h after exposure to DZN, diazoxone, or CPF-oxone (200 μM), no cytotoxicity was found in H9c2 cells [ 51 ]. However, CPF induced cardiotoxicity in H9c2 at a dose of over 100 μM.…”

Section: Organophosphorus Compound-induced Cardiovascular Diseasesmentioning

confidence: 99%

“…However, CPF induced cardiotoxicity in H9c2 at a dose of over 100 μM. Phenyl-saligenin phosphate (PSP) induced cytotoxicity in mitotic and differentiated H9c2 cells by activating JNK1/2 signaling but not ERK1/2 signaling, suggesting the proapoptotic role of PSP for the induction of cell death [ 51 ].…”

Section: Organophosphorus Compound-induced Cardiovascular Diseasesmentioning

confidence: 99%

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Organophosphorus Compounds and MAPK Signaling Pathways

Farkhondeh

Buhrmann

Pourbagher‐Shahri

et al. 2020

IJMS

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The molecular signaling pathways that lead to cell survival/death after exposure to organophosphate compounds (OPCs) are not yet fully understood. Mitogen-activated protein kinases (MAPKs) including the extracellular signal-regulated protein kinase (ERK), the c-Jun NH2-terminal kinase (JNK), and the p38-MAPK play the leading roles in the transmission of extracellular signals into the cell nucleus, leading to cell differentiation, cell growth, and apoptosis. Moreover, exposure to OPCs induces ERK, JNK, and p38-MAPK activation, which leads to oxidative stress and apoptosis in various tissues. However, the activation of MAPK signaling pathways may differ depending on the type of OPCs and the type of cell exposed. Finally, different cell responses can be induced by different types of MAPK signaling pathways after exposure to OPCs.

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Phenyl Saligenin Phosphate Induced Caspase-3 and c-Jun N-Terminal Kinase Activation in Cardiomyocyte-Like Cells

Cited by 5 publications

References 42 publications

Neurite outgrowth inhibitory levels of organophosphates induce tissue transglutaminase activity in differentiating N2a cells: evidence for covalent adduct formation

Neurite outgrowth inhibitory levels of organophosphates induce tissue transglutaminase activity in differentiating N2a cells: evidence for covalent adduct formation

Proteomic analysis of the monkey hippocampus for elucidating ischemic resistance

Organophosphorus Compounds and MAPK Signaling Pathways

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