Untitled

Sen, Prosenjit; Mukherjee, Sebanti; Ray, Deepshikha; Raha, Sanghamitra

doi:10.1023/a:1026020101379

Cited by 88 publications

(24 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The PI3K product, phosphatidylinositol 3,4,5-triphosphate activates phosphatidylinositol-dependent kinase, which activates AKT. Activation of AKT protects cells from apoptosis induced by TNF-␣ (8, 23, 30, 31) by phosphorylating MDM2, AFX, FKHR, mTOR, and BAD (46,47). Reciprocally, ceramide has been shown to induce dephosphorylation of AKT through activation of PP2A serine/threonine protein phosphatase; thus, S1P and ceramide exert opposing effects on AKT, and the action of ceramidase is expected to abrogate the effects of ceramide and enhance the effects of S1P.…”

Section: Protective Effect Of Asmase Inhibition Against Hepatocyte Apmentioning

confidence: 99%

Roles for C16-ceramide and Sphingosine 1-Phosphate in Regulating Hepatocyte Apoptosis in Response to Tumor Necrosis Factor-α

Osawa

Uchinami

Bielawski

et al. 2005

Journal of Biological Chemistry

212

149

View full text Add to dashboard Cite

Tumor necrosis factor (TNF)-␣ signals cell death and simultaneously induces the generation of ceramide, which is metabolized to sphingosine and sphingosine 1-phosphate (S1P) by ceramidase (CDase) and sphingosine kinase. Because the dynamic balance between the intracellular levels of ceramide and S1P (the "ceramide/ S1P rheostat") may determine cell survival, we investigated these sphingolipid signaling pathways in TNF-␣-induced apoptosis of primary hepatocytes. Endogenous C 16 -ceramide was elevated during TNF-␣-induced apoptosis in both rat and mouse primary hepatocytes. The putative acid sphingomyelinase (ASMase) inhibitor imipramine inhibited TNF-␣-induced apoptosis and C 16 -ceramide increase as did the knock out of ASMase. Overexpression of neutral CDase (NCDase) inhibited the TNF-␣-induced increase of C 16 -ceramide and apoptosis in rat primary hepatocytes. Moreover, NCDase inhibited liver injury and hepatocyte apoptosis in mice treated with D-galactosamine plus TNF-␣. This protective effect was abrogated by the sphingosine kinase inhibitor N,Ndemethylsphingosine, suggesting that the survival effect of NCDase is due to not only C 16 -ceramide reduction but also S1P formation. Administration of S1P or overexpression of NCDase activated the pro-survival kinase AKT, and overexpression of dominant negative AKT blocked the survival effect of NCDase. In conclusion, activation of ASMase and generation of C 16 -ceramide contributed to TNF-␣-induced hepatocyte apoptosis. NCDase prevented apoptosis both by reducing C 16 -ceramide and by activation of AKT through S1P formation. Therefore, the cross-talk between sphingolipids and AKT pathway may determine hepatocyte apoptosis by TNF-␣.

show abstract

Section: Protective Effect Of Asmase Inhibition Against Hepatocyte Apmentioning

confidence: 99%

Roles for C16-ceramide and Sphingosine 1-Phosphate in Regulating Hepatocyte Apoptosis in Response to Tumor Necrosis Factor-α

Osawa

Uchinami

Bielawski

et al. 2005

Journal of Biological Chemistry

212

149

View full text Add to dashboard Cite

show abstract

“…Clearly, the identification of these substrates represents the next most important stage in understanding the role of PKB in glucose uptake. More than 30 PKB substrates have been identified to date (Table 1) [20,21]. At present, there is only evidence for an involvement of two of these in insulin-stimulated glucose transport.…”

mentioning

confidence: 99%

Role of protein kinase B in insulin-regulated glucose uptake

Welsh

Hers

Berwick

et al. 2005

Biochemical Society Transactions

110

View full text Add to dashboard Cite

The activation of protein kinase B (or Akt) plays a central role in the stimulation of glucose uptake by insulin. Currently, however, numerous questions remain unanswered regarding the role of this kinase in bringing about this effect. For example, we do not know precisely where in the GLUT4 trafficking pathway this kinase acts. Nor do we know which protein substrates are responsible for mediating the effects of protein kinase B, although two recently identified proteins (AS160 and PIKfyve) may play a role. This paper addresses these important questions by reviewing recent progress in the field.

show abstract

“…Moreover, we have also shown here that LMW-Fuc treatment after LPS challenge is also capable of inhibiting the fMLP effect on PMN cytoskeleton rearrangement, preventing fMLP stimulation, as can be observed in online supplementary Figure S7. Supporting this hypothesis, LMW-Fuc also inhibited the LPS/fMLP-induced activation of AKT, a key component of the canonical PI3K/AKT pathway involved in the regulation of actin polymerization and other cytoskeleton-associated events [28]. When activated, AKT phosphorylates the pro-apoptotic protein Bad, leading to Bad degradation [29].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Microparticle Release and Pro-Inflammatory Properties of Activated Human Polymorphonuclear Neutrophils by LMW Fucoidan

et al. 2018

View full text Add to dashboard Cite

Exposition of neutrophils (polymorphonuclear neutrophils, PMNs) to bacterial products triggers exacerbated activation of these cells, increasing their harmful effects on host tissues. We evaluated the possibility of interfering with the classic immune innate responses of human PMNs exposed to bacterial endotoxin (lipopolysaccharide, LPS), and further stimulated with bacterial formyl peptide (N-formyl-methionine-leucine-phenylalanine, fMLP). We showed that the low- molecular-weight fucoidan (LMW-Fuc), a polysaccharide extracted from brown algae, attenuated the exacerbated activation induced by fMLP on LPS-primed PMNs, in vitro, impairing chemotaxis, NET formation, and the pro-survival and pro-oxidative effects. LMW-Fuc also inhibited the activation of canonical signaling pathways, AKT, bad, p47phox and MLC, activated by the exposition of PMN to bacterial products. The activation of PMN by sequential exposure to LPS and fMLP induced the release of L-selectin⁺ microparticles, which were able to trigger extracellular reactive oxygen species production by fresh PMNs and macrophages. Furthermore, we observed that LMW-Fuc inhibited microparticle release from activated PMN. In vivo experiments showed that circulating PMN-derived microparticles could be detected in mice exposed to bacterial products (LPS/fMLP), being downregulated in animals treated with LMW-Fuc. The data highlight the autocrine and paracrine role of pro-inflammatory microparticles derived from activated PMN and demonstrate the anti-inflammatory effects of LMW-Fuc on these cells.

show abstract

Untitled

Cited by 88 publications

References 50 publications

Roles for C16-ceramide and Sphingosine 1-Phosphate in Regulating Hepatocyte Apoptosis in Response to Tumor Necrosis Factor-α

Roles for C16-ceramide and Sphingosine 1-Phosphate in Regulating Hepatocyte Apoptosis in Response to Tumor Necrosis Factor-α

Role of protein kinase B in insulin-regulated glucose uptake

Downregulation of Microparticle Release and Pro-Inflammatory Properties of Activated Human Polymorphonuclear Neutrophils by LMW Fucoidan

Contact Info

Product

Resources

About