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1.
Int J Mol Sci ; 22(20)2021 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-34681720

RESUMEN

Physiological selenium (Se) levels counteract excessive inflammation, with selenoproteins shaping the immunoregulatory cytokine and lipid mediator profile. How exactly differentiation of monocytes into macrophages influences the expression of the selenoproteome in concert with the Se supply remains obscure. THP-1 monocytes were differentiated with phorbol 12-myristate 13-acetate (PMA) into macrophages and (i) the expression of selenoproteins, (ii) differentiation markers, (iii) the activity of NF-κB and NRF2, as well as (iv) lipid mediator profiles were analyzed. Se and differentiation affected the expression of selenoproteins in a heterogeneous manner. GPX4 expression was substantially decreased during differentiation, whereas GPX1 was not affected. Moreover, Se increased the expression of selenoproteins H and F, which was further enhanced by differentiation for selenoprotein F and diminished for selenoprotein H. Notably, LPS-induced expression of NF-κB target genes was facilitated by Se, as was the release of COX- and LOX-derived lipid mediators and substrates required for lipid mediator biosynthesis. This included TXB2, TXB3, 15-HETE, and 12-HEPE, as well as arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Our results indicate that Se enables macrophages to accurately adjust redox-dependent signaling and thereby modulate downstream lipid mediator profiles.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , Selenio/farmacología , Transducción de Señal/efectos de los fármacos , Acetato de Tetradecanoilforbol/farmacología , Ácido Araquidónico/metabolismo , Línea Celular , Ácido Eicosapentaenoico/metabolismo , Humanos , Lipopolisacáridos/farmacología , Macrófagos/citología , Macrófagos/metabolismo , FN-kappa B/metabolismo , Oxidación-Reducción , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Selenio/química , Selenoproteínas/metabolismo , Tromboxano B2/metabolismo
2.
Antioxidants (Basel) ; 9(11)2020 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-33198336

RESUMEN

N-acetylcysteine (NAC) is a frequently prescribed drug and known for its metal chelating capability. However, to date it is not well characterized whether NAC intake affects the homeostasis of essential trace elements. As a precursor of glutathione (GSH), NAC also has the potential to modulate the cellular redox homeostasis. Thus, we aimed to analyze effects of acute and chronic NAC treatment on the homeostasis of copper (Cu) and zinc (Zn) and on the activity of the redox-sensitive transcription factor Nrf2. Cells were exposed to 1 mM NAC and were co-treated with 50 µM Cu or Zn. We showed that NAC treatment reduced the cellular concentration of Zn and Cu. In addition, NAC inhibited the Zn-induced Nrf2 activation and limited the concomitant upregulation of cellular GSH concentrations. In contrast, mice chronically received NAC via drinking water (1 g NAC/100 mL). Cu and Zn concentrations were decreased in liver and spleen. In the duodenum, NQO1, TXNRD, and SOD activities were upregulated by NAC. All of them can be induced by Nrf2, thus indicating a putative Nrf2 activation. Overall, NAC modulates the homeostasis of Cu and Zn both in vitro and in vivo and accordingly affects the cellular redox balance.

3.
Antioxidants (Basel) ; 7(1)2018 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-29364189

RESUMEN

Polyphenols are antioxidant ingredients in apples and are related to human health because of their free radical scavenging activities. The polyphenolic profiles of old and new apple cultivars (n = 15) were analysed using high-performance liquid chromatography (HPLC) with diode array detection (DAD). The in vitro antioxidant capacity was determined by total phenolic content (TPC) assay, hydrophilic trolox equivalent antioxidant capacity (H-TEAC) assay and hydrophilic oxygen radical absorbance (H-ORAC) assay. Twenty polyphenolic compounds were identified in all investigated apples by HPLC analysis. Quercetin glycosides (203 ± 108 mg/100 g) were the main polyphenols in the peel and phenolic acids (10 ± 5 mg/100 g) in the flesh. The calculated relative contribution of single compounds indicated flavonols (peel) and vitamin C (flesh) as the major contributors to the antioxidant capacity, in all cultivars investigated. The polyphenolic content (HPLC data) of the flesh differed significantly between old (29 ± 7 mg/100 g) and new (13 ± 4 mg/100 g) cultivars, and the antioxidant capacity of old apple cultivars was up to 30% stronger compared to new ones.

4.
Mol Pain ; 8: 83, 2012 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-23146666

RESUMEN

BACKGROUND: Proopiomelanocortin (POMC)-derived beta-endorphin1-31 from immune cells can inhibit inflammatory pain. Here we investigated cytokine signaling pathways regulating POMC gene expression and beta-endorphin production in lymphocytes to augment such analgesic effects. RESULTS: Interleukin-4 dose-dependently elevated POMC mRNA expression in naïve lymph node-derived cells in vitro, as determined by real-time PCR. This effect was neutralized by janus kinase (JAK) inhibitors. Transfection of Signal Transducer and Activator of Transcription (STAT) 1/3 but not of STAT6 decoy oligonucleotides abolished interleukin-4 induced POMC gene expression. STAT3 was phosphorylated in in vitro interleukin-4 stimulated lymphocytes and in lymph nodes draining inflamed paws in vivo. Cellular beta-endorphin increased after combined stimulation with interleukin-4 and concanavalin A. Consistently, in vivo reduction of inflammatory pain by passively transferred T cells improved significantly when donor cells were pretreated with interleukin-4 plus concanavalin A. This effect was blocked by naloxone-methiodide. CONCLUSION: Interleukin-4 can amplify endogenous opioid peptide expression mediated by JAK-STAT1/3 activation in mitogen-activated lymphocytes. Transfer of these cells leads to inhibition of inflammatory pain via activation of peripheral opioid receptors.


Asunto(s)
Inflamación/metabolismo , Janus Quinasa 3/metabolismo , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Dolor/metabolismo , Proopiomelanocortina/genética , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Células Cultivadas , Concanavalina A/farmacología , Inflamación/tratamiento farmacológico , Interleucina-4/farmacología , Interleucina-4/uso terapéutico , Janus Quinasa 3/genética , Masculino , Naloxona/análogos & derivados , Naloxona/farmacología , Dolor/tratamiento farmacológico , Compuestos de Amonio Cuaternario/farmacología , ARN Mensajero , Ratas , Ratas Wistar , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT3/genética
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