Interleukin‐6 promotes 2‐deoxyglucose uptake through p44/42 MAPKs activation via Ca<sup>2+</sup>/PKC and EGF receptor in primary cultured chicken hepatocytes

Lee, Yu Jin; Han, Ho Jae

doi:10.1002/jcp.21641

Cited by 8 publications

(7 citation statements)

References 57 publications

(55 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, also interleukin-induced activation of STAT3 has been shown to be essential for the expression of GLUTs, glucose uptake, and activation of the glycolytic pathway (21). Conversely, STAT3 inhibitors have been shown to block GLUT2 expression and 2DG uptake (22). Consistent with these observations, we found decreasing tumoral 18 F-FDG uptake after vandetanib-dependent downregulation of STAT3 and the Grb7 and Grb10 pathways.…”

Section: Metabolic Effects Of Vandetanibsupporting

confidence: 90%

“…Increased Ras GTPase expression leads to increased glucose transport, mainly because of increased GLUT transcription (19,20). Finally, activation of STAT3 significantly induces GLUT expression and glucose uptake (21,22). This possible relationship between RET signaling and tumor metabolic activity is of clinical interest because tumor glucose metabolism can be assessed quantitatively and noninvasively by PET with the glucose analog 18 F-FDG.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Metabolic Imaging Allows Early Prediction of Response to Vandetanib

Walter¹,

Benz²,

Hildebrandt³

et al. 2011

J Nucl Med

View full text Add to dashboard Cite

The RET (rearranged-during-transfection protein) protooncogene triggers multiple intracellular signaling cascades regulating cell cycle progression and cellular metabolism. We therefore hypothesized that metabolic imaging could allow noninvasive detection of response to the RET inhibitor vandetanib in vivo. Methods: The effects of vandetanib treatment on the fullgenome expression and the metabolic profile were analyzed in the human medullary thyroid cancer cell line TT. In vitro, transcriptional changes of pathways regulating cell cycle progression and glucose, dopa, and thymidine metabolism were correlated to the results of cell cycle analysis and the uptake of 3 H-deoxyglucose, 3 H-3,4-dihydroxy-L-phenylalanine, and 3 H-thymidine under vandetanib treatment. In vivo, the tumor metabolism under vandetanib was monitored by small-animal PET of tumor-bearing mice. Results: Vandetanib treatment resulted in the transcriptional downregulation of various effector pathways with consecutive downregulation of cyclin expression and a G 0 /G 1 arrest. In vitro, vandetanib treatment resulted in the decreased expression of genes regulating glucose, 3,4-dihydroxy-L-phenylalanine, and thymidine metabolism, with a subsequent reduction in the functional activity of the corresponding pathways. In vivo, metabolic imaging with PET was able to assess changes in the tumoral glucose metabolism profile as early as 3 d after initiation of vandetanib treatment. Conclusion: We describe a metabolic imaging approach for the noninvasive detection of successful vandetanib treatment. Our results suggest that PET may be useful for identifying patients who respond to vandetanib early in the course of treatment. TheRET(rearranged-duri ng-transfection protein) protooncogene, located on chromosome 10q11.2, encodes for a tyrosine kinase of the cadherin superfamily that activates multiple intracellular signaling cascades regulating cell survival, differentiation, proliferation, migration, and chemotaxis (1). Gain-of-function mutations in the RET gene result in uncontrolled growth and cause human cancers and cancer syndromes, such as Hürthle cell cancer, sporadic papillary thyroid carcinoma, familial medullary thyroid carcinoma, and multiple endocrine neoplasia types 2A and 2B (2).The signaling pathways downstream of RET are activated by autophosphorylation of several tyrosine and serine residues (Fig. 1A) and regulate several genes involved in tumor progression (3). Among other effects, activated Rac (Ras-related C3 botulinum toxin substrate) (4), STAT3 (signal transducer and activator of transcription 3) (5), Src (v-src sarcoma [Schmidt-Ruppin A-2] viral oncogene homolog) (5), Ras (v-Ha-ras Harvey rat sarcoma viral oncogene homolog) (6), and PI3K (phosphatidylinositol-3-kinase) (7) each results in the upregulation of cyclin activity, which consequently leads to accelerated cell cycle progression (8). Growth factor receptor-bound proteins 7 and 10 (Grb7 and Grb10) presumably contribute to the invasive cell potential (9), whereas phospholipase Cg (PLCg...

show abstract

Section: Metabolic Effects Of Vandetanibsupporting

confidence: 90%

mentioning

confidence: 99%

Metabolic Imaging Allows Early Prediction of Response to Vandetanib

Walter¹,

Benz²,

Hildebrandt³

et al. 2011

J Nucl Med

View full text Add to dashboard Cite

show abstract

“…In agreement with these results, suppression of ERK by grape powder extract attenuated TNF␣-induced insulin resistance [47], and JNK blockage could also mediate the inhibition of IRS-1 serine phosphorylation [22], contributing to the stimulation of the hepatic insulin sensitivity, whereas p38 seemed to moderately affect p-(Ser)-IRS-1 levels [51]. Moreover, oxidative stress inhibited insulin-stimulated glucose transport in adipocytes, which was reversed by pre-incubation with an antioxidant [53], and a role for ERK on the glucose uptake has been reported in hepatic cells [54]. Interestingly, impaired glucose utilization could be provoked because of ROS interfering with insulin signalling cascade [55].…”

Section: Discussionmentioning

confidence: 95%

Cocoa flavonoids protect hepatic cells against high‐glucose‐induced oxidative stress: Relevance of MAPKs

Cordero-Herrera

Martín

Goya

et al. 2015

Molecular Nutrition Food Res

View full text Add to dashboard Cite

Scope Oxidative stress plays a main role in the pathogenesis of type 2 diabetes mellitus. Cocoa and (‐)‐epicatechin (EC), a main cocoa flavanol, have been suggested to exert beneficial effects in type 2 diabetes mellitus because of their protective effects against oxidative stress and insulin‐like properties. In this study, the protective effect of EC and a cocoa phenolic extract (CPE) against oxidative stress induced by a high‐glucose challenge, which causes insulin resistance, was investigated on hepatic HepG2 cells. Methods and results Oxidative status, phosphorylated mitogen‐activated protein kinases (MAPKs), nuclear factor E2 related factor 2 (Nrf2) and p‐(Ser)‐IRS‐1 expression, and glucose uptake were evaluated. EC and CPE regulated antioxidant enzymes and activated extracellular‐regulated kinase and Nrf2. EC and CPE pre‐treatment prevented high‐glucose‐induced antioxidant defences and p‐MAPKs, and maintained Nrf2 stimulation. The presence of selective MAPK inhibitors induced changes in redox status, glucose uptake, p‐(Ser)‐ and total IRS‐1 levels that were observed in CPE‐mediated protection. Conclusion EC and CPE recovered redox status of insulin‐resistant HepG2 cells, suggesting that the functionality in EC‐ and CPE‐treated cells was protected against high‐glucose‐induced oxidative insult. CPE beneficial effects on redox balance and insulin resistance were mediated by targeting MAPKs.

show abstract

“…Hepatocytes, the major cellular constituent of the liver, are highly susceptible to locally released cytokines. They also express a variety of cytokine receptors including receptors for IL-1b, TNF-a, and IL-6, suggesting that they have an intrinsic ability to respond to cytokines Hoek & Rubin, 1998;Henkel et al, 2009;Suh et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Silybin inhibits interleukin‐1β‐induced production of pro‐inflammatory mediators in canine hepatocyte cultures

Hasenwinkel

Frondoza

2011

Vet Pharm & Therapeutics

View full text Add to dashboard Cite

Hepatocytes are highly susceptible to cytokine stimulation and are fundamental to liver function. We established primary canine hepatocyte cultures to study effects of anti-inflammatory agents with hepatoprotective properties. Hepatocyte cultures were incubated with control media alone, silybin (SB), or the more bioavailable silybin-phosphatidylcholine complex (SPC), followed by activation with interleukin-1 beta (IL-1β; 10 ng/mL). Inflammatory response was measured by prostaglandin E2 (PGE(2) ), interleukin-8 (IL-8), and monocyte chemotactic protein-1 (MCP-1) production and also nuclear factor-kappa B (NF-κB) translocation. Hepatocyte cultures continued production of the phenotypic marker albumin for more than 7 days in culture. IL-1β exposure increased PGE(2) , IL-8, and MCP-1 production, which was paralleled by NF-κB translocation from the cytoplasm to the nucleus. Pretreatment with SB and SPC significantly inhibited IL-1β-induced production of pro-inflammatory markers and attenuated NF-κB nuclear translocation. We demonstrate for the first time that primary canine hepatocyte cultures can be maintained in culture without phenotypic loss. The observation that hepatocyte cultures respond to pro-inflammatory IL-1β activation indicates hepatocytes as primary cellular targets of extrinsic IL-1β. The ability of SB and SPC to inhibit hepatocyte culture activation by IL-1β reinforces the notion of their hepatoprotective effects. Our primary canine hepatocyte culture model facilitates identification of hepatoprotective agents and their mechanism of action.

show abstract

Interleukin‐6 promotes 2‐deoxyglucose uptake through p44/42 MAPKs activation via Ca²⁺/PKC and EGF receptor in primary cultured chicken hepatocytes

Cited by 8 publications

References 57 publications

Metabolic Imaging Allows Early Prediction of Response to Vandetanib

Metabolic Imaging Allows Early Prediction of Response to Vandetanib

Cocoa flavonoids protect hepatic cells against high‐glucose‐induced oxidative stress: Relevance of MAPKs

Silybin inhibits interleukin‐1β‐induced production of pro‐inflammatory mediators in canine hepatocyte cultures

Contact Info

Product

Resources

About

Interleukin‐6 promotes 2‐deoxyglucose uptake through p44/42 MAPKs activation via Ca2+/PKC and EGF receptor in primary cultured chicken hepatocytes

Cited by 8 publications

References 57 publications

Metabolic Imaging Allows Early Prediction of Response to Vandetanib

Metabolic Imaging Allows Early Prediction of Response to Vandetanib

Cocoa flavonoids protect hepatic cells against high‐glucose‐induced oxidative stress: Relevance of MAPKs

Silybin inhibits interleukin‐1β‐induced production of pro‐inflammatory mediators in canine hepatocyte cultures

Contact Info

Product

Resources

About

Interleukin‐6 promotes 2‐deoxyglucose uptake through p44/42 MAPKs activation via Ca²⁺/PKC and EGF receptor in primary cultured chicken hepatocytes