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Salvatore Cuzzocrea - One of the best experts on this subject based on the ideXlab platform.

  • The Cyclopentenone Prostaglandin 15-deoxyΔ^12,14-Prostaglandin J_2 attenuates the development of zymosan-induced shock
    Intensive Care Medicine, 2005
    Co-Authors: Stefania Marzocco, Emanuela Mazzon, Rosanna Di Paola, Domenico Britti, Tiziana Genovese, Aldo Pinto, Giuseppina Autore, Salvatore Cuzzocrea
    Abstract:

    Objective Multiple-organ failure (MOF) is defined as the progressive deterioration in function which occurs in several organs or systems in patients with septic shock, multiple trauma, severe burns, or pancreatitis. This study investigated the effect of 15-deoxy-Δ^12,14-PGJ_2 (15d-PGJ_2), a PPAR-γ ligand, in a model of zymosan-induced nonseptic shock in mice. Materials and methods Mice were randomly assigned to one of four groups ( n =10 each) and treated i.p. as follows: group 1, zymosan (500 mg/kg suspended in saline solution) and vehicle (10% DMSO); group 2, zymosan (500 mg/kg suspended in saline solution) plus 15d-PGJ_2 (30 µg/kg, suspended in 10% DMSO) 1 h before and 6 h after zymosan administration; group 3, 15d-PGJ_2 (30 µg/kg, suspended in 10% DMSO; group 4, vehicle for PGJ_2 (10% DMSO) always 1 h before and 6 h after saline administration. After 18 h mice were killed and tissues and biological fluids used for biochemical, immunohistochemical, and histological analysis. Measurements and results 15d-PGJ_2 inhibited the inflammatory response and significantly reduced peritoneal mononuclear cell infiltration and histological injury in mice. A significant protection was demonstrated in kidney, liver, and pancreas injury by the reduction in amylase, lipase, creatinine, AST, ALT, bilirubin, and alkaline phosphatase levels. 15d-PGJ_2 also reduced the appearance of nitrotyrosine in the inflamed intestinal tissues. Histological examination revealed a significant reduction in zymosan-induced intestinal damage in 15d-PGJ_2 treated mice. Conclusions Our findings demonstrate that 15d-PGJ_2 exerts potent anti-inflammatory effects on zymosan-induced shock.

  • the Cyclopentenone Prostaglandin 15 deoxyδ12 14 Prostaglandin j2 attenuates the development of zymosan induced shock
    Intensive Care Medicine, 2005
    Co-Authors: Stefania Marzocco, Emanuela Mazzon, Rosanna Di Paola, Domenico Britti, Tiziana Genovese, Aldo Pinto, Giuseppina Autore, Salvatore Cuzzocrea
    Abstract:

    Objective Multiple-organ failure (MOF) is defined as the progressive deterioration in function which occurs in several organs or systems in patients with septic shock, multiple trauma, severe burns, or pancreatitis. This study investigated the effect of 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2), a PPAR-γ ligand, in a model of zymosan-induced nonseptic shock in mice.

  • the Cyclopentenone Prostaglandin 15 deoxy δ12 14 Prostaglandin j2 ameliorates ischemic acute renal failure
    Cardiovascular Research, 2004
    Co-Authors: Prabal K. Chatterjee, Salvatore Cuzzocrea, Domenico Britti, Nimesh S A Patel, Paul A J Brown, Keith N Stewart, Helder Motafilipe, Wolfgang Eberhardt, Josef Pfeilschifter, Christoph Thiemermann
    Abstract:

    Objective: Here we investigate the effects of the endogenous Prostaglandin D2 metabolite 15-deoxy-Δ12,14-Prostaglandin J2, on the renal dysfunction and injury caused by ischemia/reperfusion of the kidney. Methods: Male Wistar rats, subjected to bilateral renal ischemia for 45 min followed by reperfusion for up to 48 h, were administered 15-deoxy-Δ12,14-Prostaglandin J2 (1 mg/kg, intravenously) 5 min prior to and again after 3 or 12 h reperfusion. Results: 15-deoxy-Δ12,14-Prostaglandin J2 significantly reduced (i) renal and tubular dysfunction (serum urea and creatinine levels, creatinine clearance, fractional excretion of Na+ (FENa)), (ii) tubular and reperfusion-injury (urinary N -acetyl-β-d-glucosaminidase, aspartate aminotransferase (ASP) and γ-glutamyltransferase (γ-GT)) and (iii) histological evidence of renal injury. 15-deoxy-Δ12,14-Prostaglandin J2 also improved renal function (plasma creatinine levels) and reduced the histological signs of renal injury (after 48 h reperfusion). Administration of 15-deoxy-Δ12,14-Prostaglandin J2 markedly reduced the expression of inducible nitric oxide synthase (iNOS) and intercellular adhesion molecule-1 during reperfusion (determined using immunohistochemistry). Immunohistochemical analysis of p65 translocation and Western blot analysis of IκB-α degradation revealed that 15-deoxy-Δ12,14-Prostaglandin J2 inhibited the activation of nuclear factor (NF)-κB in renal cells. Subsequently, 15d-PGJ2 was able to significantly reduce nitric oxide production during renal ischemia/reperfusion and by primary cultures of rat proximal tubular (PT) cells incubated with interferon-γ and bacterial lipopolysaccharide (LPS) in combination. Conclusions: We demonstrate here, for the first time, that 15-deoxy-Δ12,14-Prostaglandin J2 significantly reduces renal ischemia/reperfusion-injury via reduction of pro-inflammatory gene expression during reperfusion subsequent to the inhibition of the activation of NF-κB.

  • the Cyclopentenone Prostaglandin 15 deoxy δ12 14 pgj2 attenuates the development of colon injury caused by dinitrobenzene sulphonic acid in the rat
    British Journal of Pharmacology, 2003
    Co-Authors: Salvatore Cuzzocrea, Nicole S. Wayman, Emanuela Mazzon, Laura Dugo, Rosanna Di Paola, Ivana Serraino, Prabal K. Chatterjee, Angela Ianaro, Barbara Pisano, Massimo Di Rosa
    Abstract:

    Inflammatory bowel disease (IBD) is characterized by oxidative and nitrosative stress, leukocyte infiltration, and increased expression of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) in the colon. Recent evidence also suggests that the Cyclopentenone Prostaglandin (PG) 15-deoxy-Δ12,14-PGJ2 (15d- PGJ2) functions as an early anti-inflammatory signal. The aim of the present paper is to investigate the effects of 15d-PGJ2 in rats subjected to experimental colitis. Colitis was induced in rats by intra-colonic instillation of dinitrobenzene sulphonic acid (DNBS). 15d-PGJ2 was administered daily as intraperitoneal injection (20 or 40 μg kg−1). On day 4, animals were sacrificed and tissues were taken for histological and biochemical analysis. 15d-PGJ2 significantly reduced the degree of haemorrhagic diarrhoea and weight loss caused by administration of DNBS. 15d-PGJ2 also caused a substantial reduction of (i) the degree of colonic injury, (ii) the rise in myeloperoxidase (MPO) activity (mucosa), (iii) the increase in the tissue levels of malondialdehyde (MDA) and (iv) of the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β). Furthermore, 15d-PGJ2 reduced the increase in immunohistochemical staining for (i) inducible nitric oxide synthase (iNOS), (ii) nitrotyrosine and (iii) poly (ADP-ribose) polymerase (PARP), as well as (iv) the increased expression of ICAM-1 caused by DNBS in the colon. Electrophoresis mobility shift assay (EMSA) of inflamed colon revealed that 15d- PGJ2 also caused a substantial reduction of the activation of nuclear factor-kappaB (NF-κB). Furthermore, 15d-PGJ2 stimulates the activation of heat shock protein 72 (hsp72) in the inflamed colon, as assessed by Western blot analysis. In conclusion, 15d-PGJ2 reduces the development of experimental colitis. British Journal of Pharmacology (2003) 138, 678–688. doi:10.1038/sj.bjp.0705077

  • The Cyclopentenone Prostaglandin 15-deoxy-Delta(12,14)-Prostaglandin J(2) attenuates the development of acute and chronic inflammation.
    Molecular Pharmacology, 2002
    Co-Authors: Salvatore Cuzzocrea, Nicole S. Wayman, Emanuela Mazzon, Laura Dugo, Rosanna Di Paola, Ivana Serraino, Domenico Britti, Prabal K. Chatterjee, Achille P. Caputi, Christoph Thiemermann
    Abstract:

    Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid, and thyroid hormone receptors. The PPAR-gamma receptor subtype seems to play a pivotal role in the regulation of cellular proliferation and inflammation. Recent evidence also suggests that the Cyclopentenone Prostaglandin (PG) 15-deoxyDelta(12,14)-PGJ(2) (15d-PGJ(2)), which is a metabolite of Prostaglandin D(2), functions as an endogenous ligand for PPAR-gamma. We postulated that 15d-PGJ(2) would attenuate inflammation. In the present study, we have investigated the effects of 15d-PGJ(2) of acute and chronic inflammation (carrageenan-induced pleurisy and collagen-induced arthritis, respectively) in animal models. We report for the first time, to our knowledge, that 15d-PGJ(2) (given at 10, 30, or 100 microg/kg i.p. in the pleurisy model or at 30 microg/kg i.p every 48 h in the arthritis model) exerts potent anti-inflammatory effects (e.g., inhibition of pleural exudate formation, mononuclear cell infiltration, delayed development of clinical indicators, and histological injury) in vivo. Furthermore, 15d-PGJ(2) reduced the increase in the staining (immunohistochemistry) for nitrotyrosine and poly (ADP-ribose) polymerase and the expression of inducible nitric-oxide synthase and cyclooxygenase-2 in the lungs of carrageenan-treated mice and in the joints from collagen-treated mice. Thus, 15d-PGJ(2) reduces the development of acute and chronic inflammation. Therefore, the Cyclopentenone Prostaglandin 15d-PGJ(2) may be useful in the therapy of acute and chronic inflammation.

Paulo Ivo Homem De Bittencourt - One of the best experts on this subject based on the ideXlab platform.

  • LipoCardium: Endothelium-directed Cyclopentenone Prostaglandin-based liposome formulation that completely reverses atherosclerotic lesions
    Atherosclerosis, 2007
    Co-Authors: Paulo Ivo Homem De Bittencourt, Denise Jacques Lagranha, Alexandre Maslinkiewicz, Sueli M. Senna, Angela Maria Vicente Tavares, Lisiane Paula Baldissera, Daiane Da Rocha Janner, Joelso Dos Santos Peralta, Patricia Martins Bock, Lucila Ludmila Paula Gutierrez
    Abstract:

    Atherosclerosis is a multifactorial inflammatory disease of blood vessels which decimates one in every three people in industrialized world. Despite the important newest clinical approaches, currently available strategies (e.g. nutritional, pharmacological and surgical) may only restrain the worsening of vascular disease. Since antiproliferative Cyclopentenone Prostaglandins (CP-PGs) are powerful anti-inflammatory agents, we developed a negatively charged liposome-based pharmaceutical formulation (LipoCardium) that specifically direct CP-PGs towards the injured arterial wall cells of atherosclerotic mice. In the blood stream, LipoCardium delivers its CP-PG contents only into activated arterial wall lining cells due to the presence of antibodies raised against vascular cell adhesion molecule-1 (VCAM-1), which is strongly expressed upon inflammation by endothelial cells and macrophage-foam cells as well. After 4 months in a high-lipid diet, all low-density lipoprotein receptor-deficient adult control mice died from myocardium infarction or stroke in less than 2 weeks, whereas LipoCardium-treated (2 weeks) animals (still under high-lipid diet) completely recovered from vascular injuries. In vitro studies using macrophage-foam cells suggested a tetravalent pattern for LipoCardium action: anti-inflammatory, antiproliferative (and pro-apoptotic only to foam cells), antilipogenic and cytoprotector (via heat-shock protein induction). These astonishing cellular effects were accompanied by a marked reduction in arterial wall thickness, neointimal hyperplasia and lipid accumulation, while guaranteed lifespan to be extended to the elderly age. Our findings suggest that LipoCardium may be safely tested in humans in a near future and may have conceptual implications in atherosclerosis therapy.

  • low expression of mrp1 gs x pump atpase in lymphocytes of walker 256 tumour bearing rats is associated with Cyclopentenone Prostaglandin accumulation and cancer immunodeficiency
    Cell Biochemistry and Function, 2006
    Co-Authors: Angela Kolberg, Denise Jacques Lagranha, Alexandre Maslinkiewicz, Daiane Da Rocha Janner, Rui Curi, Tatiana Gomes Rosa, Mineia Taise Puhl, Gustavo Scola, Thiago Gomes Heck, Paulo Ivo Homem De Bittencourt
    Abstract:

    Immunosuppression is a life-threatening complication of late cancer stages. In this regard, overproduction in the host plasma of the anti-inflammatory Cyclopentenone Prostaglandins (CP-PGs), which are strongly antiproliferative at high concentrations, may impair immune function. In fact, lymphoid tissues of tumour-bearing rats accumulated large amounts of CP-PGs while the tumour tissue itself did not. Expression of the CP-PG-induced 72-kDa heat shock protein (hsp70) was elevated in lymphocytes from tumour-bearing animals related to controls. As the capacity for CP-PG uptake by lymphocytes is the same as tumour cells, we investigated whether the latter could overexpress the multidrug resistance-associated protein (MRP1/GS-X pump) which extrudes CP-PGs towards the extracellular space as glutathione S-conjugates. Walker 256 tumour cells extruded 15-fold more S-conjugates than lymphocytes from the same rats (p < 0.001). This did not appear to be related to deficiency in lymphocyte glutathione (GSH) metabolism, since the major GSH metabolic routes are consistent with CP-PG conjugation in lymphocytes. This was not the case, however, for the MRP1/GS-X pump activity in lymphocyte membranes (in pmol/min/mg protein: 3.1 ± 1.7 from normal rats, 0.2 ± 0.2 from tumour-bearing animals vs 64.3 ± 7.0 in tumour cells) which was confirmed by Western blot analysis for MRP1 protein. Transfection of lymphocytes with MRP1 gene completely abolished CP-PG (0–40 μM) toxicity. Taken together, these findings suggest that CP-PG accumulation in lymphocytes may be, at least partially, responsible for cancer immunodeficiency. Clinical approaches for overexpressing MRP1/GS-X pump in lymphocytes could then play a role as a tool for the management of cancer therapeutics. Copyright © 2005 John Wiley & Sons, Ltd.

  • Low expression of MRP1/GS-X pump ATPase in lymphocytes of Walker 256 tumour-bearing rats is associated with Cyclopentenone Prostaglandin accumulation and cancer immunodeficiency.
    Cell Biochemistry and Function, 2005
    Co-Authors: Angela Kolberg, Denise Jacques Lagranha, Alexandre Maslinkiewicz, Daiane Da Rocha Janner, Rui Curi, Tatiana Gomes Rosa, Mineia Taise Puhl, Gustavo Scola, Thiago Gomes Heck, Paulo Ivo Homem De Bittencourt
    Abstract:

    Immunosuppression is a life-threatening complication of late cancer stages. In this regard, overproduction in the host plasma of the anti-inflammatory Cyclopentenone Prostaglandins (CP-PGs), which are strongly antiproliferative at high concentrations, may impair immune function. In fact, lymphoid tissues of tumour-bearing rats accumulated large amounts of CP-PGs while the tumour tissue itself did not. Expression of the CP-PG-induced 72-kDa heat shock protein (hsp70) was elevated in lymphocytes from tumour-bearing animals related to controls. As the capacity for CP-PG uptake by lymphocytes is the same as tumour cells, we investigated whether the latter could overexpress the multidrug resistance-associated protein (MRP1/GS-X pump) which extrudes CP-PGs towards the extracellular space as glutathione S-conjugates. Walker 256 tumour cells extruded 15-fold more S-conjugates than lymphocytes from the same rats (p 

  • Effects of the antiproliferative Cyclopentenone Prostaglandin A1 on glutathione metabolism in human cancer cells in culture.
    IUBMB Life, 1998
    Co-Authors: Paulo Ivo Homem De Bittencourt, C.k. Miyasaka, Rui Curi, John F. Williams
    Abstract:

    Summary. Homeostatic mechanisms for the maintenance of glutathione (GSH) are fundamental in the provision of a cellular defense against electrophilic/oxidant challenges. Cyclopentenone Prostaglandins (CP-PGs) are powerful antiproliferative endogenous substances that may act as electrophilic regulating compounds, by virtue of the presence of an c~,13-unsaturated carbonyl group in the cyclopentane ring. Nevertheless, differential resistance to CP-PG cytotoxic/cytostatic effect has been reported in different cell types. It is reported that the activity/expression of 7glutamylcysteine synthetase (T-GCS, the rate-limiting enzyme in GSH biosynthesis) can be inducibly activated by electrophiles, including CP-PGs. The response of the human cancer strains HEp-2 (larynx carcinoma) and HL-60 (promyelocytic leukemia) cells to treatment with the CP-PG PGA1 in culture was investigated by evaluating the time-course of GSH synthesis and activity of enzymes of GSH metabolism, other than 7-GCS, after PGAI addition. HEp-2 cells, being more resistant to PGA1 cytotoxic and cytostatic effects, have basal GSH levels that were 2.4-fold higher than that of HL-60 cells. The activities of GSH S-transferase (GST), glutathione reductase (GSRd) and glutathione peroxidase (GSPx) are constitutively higher in HL-60 cells than in HEp-2 cells (respectively, 17.0-, 28.5- and 12.3-fold). When challenged with PGA1, both cell types exhibited a dose-dependent rise in GSH content that was maximal 18 h after PGA1 addition and was preceded by a rise in GST and GSRd activities in both cell types (at 12 h). GSPx activity increased only in HEp-2 (PGAI evoked a 93.4%-inhibition in HL-60 cells). Moreover only HEp-2 cells exhibited early capacity to enhance GSH content (1-2 h just after PGAI addition). These results and earlier data showing that leukemia cells are sensitive to CP-PG treatment suggest that deficiencies in GSH metabolism may be strategic, , :. in therapeutic approaches to the treatment of human leukemias.

Angela Kolberg - One of the best experts on this subject based on the ideXlab platform.

  • low expression of mrp1 gs x pump atpase in lymphocytes of walker 256 tumour bearing rats is associated with Cyclopentenone Prostaglandin accumulation and cancer immunodeficiency
    Cell Biochemistry and Function, 2006
    Co-Authors: Angela Kolberg, Denise Jacques Lagranha, Alexandre Maslinkiewicz, Daiane Da Rocha Janner, Rui Curi, Tatiana Gomes Rosa, Mineia Taise Puhl, Gustavo Scola, Thiago Gomes Heck, Paulo Ivo Homem De Bittencourt
    Abstract:

    Immunosuppression is a life-threatening complication of late cancer stages. In this regard, overproduction in the host plasma of the anti-inflammatory Cyclopentenone Prostaglandins (CP-PGs), which are strongly antiproliferative at high concentrations, may impair immune function. In fact, lymphoid tissues of tumour-bearing rats accumulated large amounts of CP-PGs while the tumour tissue itself did not. Expression of the CP-PG-induced 72-kDa heat shock protein (hsp70) was elevated in lymphocytes from tumour-bearing animals related to controls. As the capacity for CP-PG uptake by lymphocytes is the same as tumour cells, we investigated whether the latter could overexpress the multidrug resistance-associated protein (MRP1/GS-X pump) which extrudes CP-PGs towards the extracellular space as glutathione S-conjugates. Walker 256 tumour cells extruded 15-fold more S-conjugates than lymphocytes from the same rats (p < 0.001). This did not appear to be related to deficiency in lymphocyte glutathione (GSH) metabolism, since the major GSH metabolic routes are consistent with CP-PG conjugation in lymphocytes. This was not the case, however, for the MRP1/GS-X pump activity in lymphocyte membranes (in pmol/min/mg protein: 3.1 ± 1.7 from normal rats, 0.2 ± 0.2 from tumour-bearing animals vs 64.3 ± 7.0 in tumour cells) which was confirmed by Western blot analysis for MRP1 protein. Transfection of lymphocytes with MRP1 gene completely abolished CP-PG (0–40 μM) toxicity. Taken together, these findings suggest that CP-PG accumulation in lymphocytes may be, at least partially, responsible for cancer immunodeficiency. Clinical approaches for overexpressing MRP1/GS-X pump in lymphocytes could then play a role as a tool for the management of cancer therapeutics. Copyright © 2005 John Wiley & Sons, Ltd.

  • Low expression of MRP1/GS-X pump ATPase in lymphocytes of Walker 256 tumour-bearing rats is associated with Cyclopentenone Prostaglandin accumulation and cancer immunodeficiency.
    Cell Biochemistry and Function, 2005
    Co-Authors: Angela Kolberg, Denise Jacques Lagranha, Alexandre Maslinkiewicz, Daiane Da Rocha Janner, Rui Curi, Tatiana Gomes Rosa, Mineia Taise Puhl, Gustavo Scola, Thiago Gomes Heck, Paulo Ivo Homem De Bittencourt
    Abstract:

    Immunosuppression is a life-threatening complication of late cancer stages. In this regard, overproduction in the host plasma of the anti-inflammatory Cyclopentenone Prostaglandins (CP-PGs), which are strongly antiproliferative at high concentrations, may impair immune function. In fact, lymphoid tissues of tumour-bearing rats accumulated large amounts of CP-PGs while the tumour tissue itself did not. Expression of the CP-PG-induced 72-kDa heat shock protein (hsp70) was elevated in lymphocytes from tumour-bearing animals related to controls. As the capacity for CP-PG uptake by lymphocytes is the same as tumour cells, we investigated whether the latter could overexpress the multidrug resistance-associated protein (MRP1/GS-X pump) which extrudes CP-PGs towards the extracellular space as glutathione S-conjugates. Walker 256 tumour cells extruded 15-fold more S-conjugates than lymphocytes from the same rats (p 

Stefania Marzocco - One of the best experts on this subject based on the ideXlab platform.

  • The Cyclopentenone Prostaglandin 15-deoxyΔ^12,14-Prostaglandin J_2 attenuates the development of zymosan-induced shock
    Intensive Care Medicine, 2005
    Co-Authors: Stefania Marzocco, Emanuela Mazzon, Rosanna Di Paola, Domenico Britti, Tiziana Genovese, Aldo Pinto, Giuseppina Autore, Salvatore Cuzzocrea
    Abstract:

    Objective Multiple-organ failure (MOF) is defined as the progressive deterioration in function which occurs in several organs or systems in patients with septic shock, multiple trauma, severe burns, or pancreatitis. This study investigated the effect of 15-deoxy-Δ^12,14-PGJ_2 (15d-PGJ_2), a PPAR-γ ligand, in a model of zymosan-induced nonseptic shock in mice. Materials and methods Mice were randomly assigned to one of four groups ( n =10 each) and treated i.p. as follows: group 1, zymosan (500 mg/kg suspended in saline solution) and vehicle (10% DMSO); group 2, zymosan (500 mg/kg suspended in saline solution) plus 15d-PGJ_2 (30 µg/kg, suspended in 10% DMSO) 1 h before and 6 h after zymosan administration; group 3, 15d-PGJ_2 (30 µg/kg, suspended in 10% DMSO; group 4, vehicle for PGJ_2 (10% DMSO) always 1 h before and 6 h after saline administration. After 18 h mice were killed and tissues and biological fluids used for biochemical, immunohistochemical, and histological analysis. Measurements and results 15d-PGJ_2 inhibited the inflammatory response and significantly reduced peritoneal mononuclear cell infiltration and histological injury in mice. A significant protection was demonstrated in kidney, liver, and pancreas injury by the reduction in amylase, lipase, creatinine, AST, ALT, bilirubin, and alkaline phosphatase levels. 15d-PGJ_2 also reduced the appearance of nitrotyrosine in the inflamed intestinal tissues. Histological examination revealed a significant reduction in zymosan-induced intestinal damage in 15d-PGJ_2 treated mice. Conclusions Our findings demonstrate that 15d-PGJ_2 exerts potent anti-inflammatory effects on zymosan-induced shock.

  • the Cyclopentenone Prostaglandin 15 deoxyδ12 14 Prostaglandin j2 attenuates the development of zymosan induced shock
    Intensive Care Medicine, 2005
    Co-Authors: Stefania Marzocco, Emanuela Mazzon, Rosanna Di Paola, Domenico Britti, Tiziana Genovese, Aldo Pinto, Giuseppina Autore, Salvatore Cuzzocrea
    Abstract:

    Objective Multiple-organ failure (MOF) is defined as the progressive deterioration in function which occurs in several organs or systems in patients with septic shock, multiple trauma, severe burns, or pancreatitis. This study investigated the effect of 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2), a PPAR-γ ligand, in a model of zymosan-induced nonseptic shock in mice.

P Saikumar - One of the best experts on this subject based on the ideXlab platform.

  • A novel role for MAP1 LC3 in nonautophagic cytoplasmic vacuolation death of cancer cells
    Oncogene, 2009
    Co-Authors: P K Singha, M A Venkatachalam, P Saikumar
    Abstract:

    Thiol reactive Cyclopentenone Prostaglandin, 15-deoxy-Δ^12,14-Prostaglandin J_2 (15d-PGJ2), induced a novel, nonapoptotic and microtubule-associated protein 1 light chain 3 (MAP1 LC3) dependent but nonautophagic form of cell death in colon, breast and prostate cancer cell lines, characterized by extensive cytoplasmic vacuolation with dilatation of endoplasmic reticulum (ER). Disruption of sulfhydryl homeostasis, which resulted in ER stress, accumulation of ubiquitinated proteins and subsequent ER dilation, contributed to peroxisome proliferator-activated receptor γ (PPARγ)-independent cell death by 15d-PGJ2. Absence of intracellular organelles in these vacuoles, shown by electron microscopy and unique fragmentation of lamin B, suggested this form of cell death to be different from autophagy and apoptosis. Cell death induced by 15d-PGJ2 is prevented by cycloheximide and actinomycin D, suggesting a requirement of new protein synthesis for death with cytoplasmic vacuolation. Here, we report for the first time that upregulation and processing of autophagy marker LC3 is an important event in nonautophagic cytoplasmic vacuolation and cell death. Notably, knockdown of LC3 conferred significant protection against 15d-PGJ2-induced cytoplasmic vacuolation and cell death, suggesting a novel role of LC3 in a death process other than autophagy.

  • A novel role for MAP1 LC3 in nonautophagic cytoplasmic vacuolation death of cancer cells
    Oncogene, 2009
    Co-Authors: R Kar, P K Singha, M A Venkatachalam, P Saikumar
    Abstract:

    Thiol reactive Cyclopentenone Prostaglandin, 15-deoxy-Δ^12,14-Prostaglandin J_2 (15d-PGJ2), induced a novel, nonapoptotic and microtubule-associated protein 1 light chain 3 (MAP1 LC3) dependent but nonautophagic form of cell death in colon, breast and prostate cancer cell lines, characterized by extensive cytoplasmic vacuolation with dilatation of endoplasmic reticulum (ER). Disruption of sulfhydryl homeostasis, which resulted in ER stress, accumulation of ubiquitinated proteins and subsequent ER dilation, contributed to peroxisome proliferator-activated receptor γ (PPARγ)-independent cell death by 15d-PGJ2. Absence of intracellular organelles in these vacuoles, shown by electron microscopy and unique fragmentation of lamin B, suggested this form of cell death to be different from autophagy and apoptosis. Cell death induced by 15d-PGJ2 is prevented by cycloheximide and actinomycin D, suggesting a requirement of new protein synthesis for death with cytoplasmic vacuolation. Here, we report for the first time that upregulation and processing of autophagy marker LC3 is an important event in nonautophagic cytoplasmic vacuolation and cell death. Notably, knockdown of LC3 conferred significant protection against 15d-PGJ2-induced cytoplasmic vacuolation and cell death, suggesting a novel role of LC3 in a death process other than autophagy.