scholarly journals Spermidine/spermine-N1-acetyltransferase ablation protects against liver and kidney ischemia-reperfusion injury in mice

2009 ◽  
Vol 296 (4) ◽  
pp. G899-G909 ◽  
Author(s):  
Kamyar Zahedi ◽  
Alex B. Lentsch ◽  
Tomohisa Okaya ◽  
Sharon Barone ◽  
Nozomu Sakai ◽  
...  
Keyword(s):  
Liver Damage ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Tubules ◽  
Wild Type ◽  
Important Mediator ◽  
Liver And Kidney ◽  
Rate Limiting ◽  
Deficient Mice ◽  
Ssat Activity

Expression of spermine/spermidine- N1-acetyltransferase (SSAT), the rate-limiting enzyme of polyamine backconversion cascade, increases after ischemia-reperfusion injuries (IRI). We hypothesized that SSAT plays an important role in the mediation of IRI. To test our hypothesis, wild-type (SSAT-wt) and SSAT-deficient (SSAT-ko) mice were subjected to liver or kidney IRI by ligation of hepatic or renal arteries. The liver and kidney content of putrescine (Put), a downstream by-product of SSAT activity, increased in SSAT-wt animals but not in SSAT-ko animals after IRI, indicating that polyamine backconversion is not functional in SSAT-deficient mice. When subjected to hepatic IRI, SSAT-ko mice were significantly protected against liver damage compared with SSAT-wt mice. Similarly, SSAT-ko animals subjected to renal IRI showed significantly greater protection against damage to kidney tubules than SSAT-wt mice. These studies indicate that SSAT-deficient animals are protected against IRI and suggest that SSAT is an important mediator of the tissue damage in IRI.

Role of α/β and γ/δ T cells in renal ischemia-reperfusion injury

2007 ◽  
Vol 293 (3) ◽  
pp. F741-F747 ◽  
Author(s):  
Kathrin Hochegger ◽  
Tobias Schätz ◽  
Philipp Eller ◽  
Andrea Tagwerker ◽  
Dorothea Heininger ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Wild Type ◽  
Renal Ischemia Reperfusion Injury ◽  
Deficient Mice

T cells have been implicated in the pathogenesis of renal ischemia-reperfusion injury (IRI). To date existing data about the role of the T cell receptor (Tcr) are contradictory. We hypothesize that the Tcr plays a prominent role in the late phase of renal IRI. Therefore, renal IRI was induced in α/β, γ/δ T cell-deficient and wild-type mice by clamping renal pedicles for 30 min and reperfusing for 24, 48, 72, and 120 h. Serum creatinine increased equally in all three groups 24 h after ischemia but significantly improved in Tcr-deficient animals compared with wild-type controls after 72 h. A significant reduction in renal tubular injury and infiltration of CD4+ T-cells in both Tcr-deficient mice compared with wild-type controls was detected. Infiltration of α/β T cells into the kidney was reduced in γ/δ T cell-deficient mice until 72 h after ischemia. In contrast, γ/δ T cell infiltration was equal in wild-type and α/β T cell-deficient mice, suggesting an interaction between α/β and γ/δ T cells. Data from γ/δ T cell-deficient mice were confirmed by in vivo depletion of γ/δ T cells in C57BL/6 mice. Whereas α/β T cell-deficient mice were still protected after 120 h, γ/δ T cell-deficient mice showed a “delayed wild-type phenotype” with a dramatic increase in kidney-infiltrating α/β, Tcr-expressing CD4+ T-cells. This report provides further evidence that α/β T cells are major effector cells in renal IRI, whereas γ/δ T cells play a role as mediator cells in the first 72 h of renal IRI.

Superoxide mediates endotoxin-induced platelet-endothelial cell adhesion in intestinal venules

2003 ◽  
Vol 284 (2) ◽  
pp. H535-H541 ◽  
Author(s):  
Wolfgang H. Cerwinka ◽  
Dianne Cooper ◽  
Christian F. Krieglstein ◽  
Chris R. Ross ◽  
Joe M. McCord ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Vascular System ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Fold Increase ◽  
Induced Response ◽  
Wild Type ◽  
Binding Properties ◽  
Platelet Endothelial Cell Adhesion ◽  
Deficient Mice

Platelets have been implicated in the pathogenesis of different diseases of the vascular system, including atherosclerosis, sepsis, and ischemia-reperfusion injury; however, relatively little is known about the factors that regulate the interactions between circulating platelets and the vessel wall. The objective of this study was to define the contribution of superoxide to LPS-induced platelet-endothelial cell (P/E) adhesion in murine intestinal venules. The adhesion of rhodamine-6G-labeled murine platelets was monitored by intravital fluorescence microscopy. Four hours after LPS administration in control [wild-type (WT)] mice, an ∼10-fold increase in P/E adhesion was detected. This response did not result from LPS-induced platelet activation. The LPS-induced P/E adhesion was greatly attenuated in NAD(P)H oxidase-deficient mice and in WT mice rendered neutropenic with anti-neutrophil serum, whereas the response was unchanged in WT mice receiving a CD18 blocking MAb or in CD18-deficient mice. A chimeric form of MnSOD that exhibits the binding properties of extracellular SOD also attenuated the LPS-induced response in WT mice. These findings indicate that neutrophil-derived superoxide plays a major role in the modulation of endotoxin-induced P/E adhesion.

scholarly journals Rolling in P-selectin-deficient mice is reduced but not eliminated in the dorsal skin

Blood ◽  
1995 ◽  
Vol 86 (9) ◽  
pp. 3487-3492 ◽  
Author(s):  
S Yamada ◽  
TN Mayadas ◽  
F Yuan ◽  
DD Wagner ◽  
RO Hynes ◽  
...  
Keyword(s):  
Shear Rate ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Dorsal Skin ◽  
Wild Type ◽  
Significant Difference ◽  
Deficient Mice

P-selectin-mediated rolling is believed to be important in the recruitment of leukocytes to tissue after ischemia-reperfusion injury. The dorsal skin chamber was used to examine differences in the rolling and stable adhesion of circulating leukocytes in subcutaneous (SC) vessels of P-selectin-deficient and age-matched wild-type mice, both under basal conditions and after ischemia-reperfusion. Rolling in the postcapillary venules in SC tissue of P-selectin-deficient mice was significantly lower than that in wild-type mice under the basal conditions and post-ischemia-reperfusion (P < .05), but was not eliminated by the deletion of the P-selectin gene. No significant difference between P-selectin-deficient and wild-type mice in shear rate or leukocyte-endothelial adhesion was observed up to 24 hours after ischemia-reperfusion. These results show that P-selectin-mediated rolling is not a prerequisite for ischemia-reperfusion-induced leukocyte-endothelial adhesion in the skin.

Contrasting roles for STAT4 and STAT6 signal transduction pathways in murine renal ischemia-reperfusion injury

2003 ◽  
Vol 285 (2) ◽  
pp. F319-F325 ◽  
Author(s):  
Naoko Yokota ◽  
Melissa Burne-Taney ◽  
Lorraine Racusen ◽  
Hamid Rabb
Keyword(s):  
T Cells ◽  
Reperfusion Injury ◽  
Cd4 T Cells ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Wild Type ◽  
Renal Ischemia Reperfusion Injury ◽  
Ifn Γ ◽  
Deficient Mice

Recent data support a modulatory role for CD4 T cells in experimental renal ischemia-reperfusion injury (IRI). CD4 T cells can functionally differentiate to either a Th1 (IFN-γ producing) or the counterbalancing Th2 (IL-4) phenotype. The enzymes signal transducers and activators of transcription (STAT) 4 and STAT6 regulate Th1 or Th2 differentiation and cytokine production, respectively. We therefore hypothesized that mice that were STAT4 deficient would be protected from renal IRI and that STAT6-deficient mice would have a more severe course. Intracellular cytokine staining of splenocytes from STAT4–/– or STAT6–/– exhibited distinct IFN-γ and IL-4 cytokine expression profiles. STAT6–/– had markedly worse renal function and tubular injury postischemia compared with wild type. STAT4–/– had only mildly improved function. Renal phagocyte infiltration and ICAM-1 upregulation were similar in STAT4–/–, STAT6–/–, and wild type. To evaluate if the mechanism of the marked worsening in the STAT6–/– mice could be due to IL-4 deficiency, IL-4-deficient mice were studied and had similar postischemic phenotype to STAT6–/– mice. These data demonstrate that the STAT6 pathway has a major protective role in renal IRI. IL-4 deficiency is a likely mechanism underlying the STAT6 effect. A “yin-yang” role for inflammation is emerging in renal IRI, similar to recent observations in atherosclerosis.

Myocardial ischemia-reperfusion injury in CD18- and ICAM-1-deficient mice

1998 ◽  
Vol 275 (6) ◽  
pp. H2300-H2307 ◽  
Author(s):  
Anthony J. Palazzo ◽  
Steven P. Jones ◽  
Wesley G. Girod ◽  
Donald C. Anderson ◽  
D. Neil Granger ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Endothelial Cell ◽  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Wild Type Mouse ◽  
Intercellular Adhesion Molecule ◽  
Wild Type ◽  
Myocardial Ischemia Reperfusion ◽  
Deficient Mice

Previous studies have demonstrated that circulating neutrophils (PMNs) contribute to the pathophysiology of myocardial ischemia-reperfusion (MI/R) injury. PMN-endothelial cell interactions are highly regulated by adhesive interactions between PMN CD11/CD18 and coronary endothelial cell intercellular adhesion molecule-1 (ICAM-1). We investigated the effects of MI/R in wild-type, CD18-, and ICAM-1-deficient (−/−) mice. Wild-type ( n = 6), CD18 −/− ( n = 6), and ICAM-1 −/− ( n = 6) mice were subjected to 30 min of myocardial ischemia and 120 min of reperfusion to determine the extent of PMN infiltration and myocardial cell necrosis. Myocardial infarction (% of the area at risk) was 45.1 ± 5.9 in wild-type mouse hearts. In contrast, the extent of myocardial infarction was significantly ( P < 0.05) reduced in the CD18 (19.3 ± 5.1%)- and ICAM-1 (17.9 ± 3.2%)-deficient mice. Similarly, PMN infiltration into the ischemic-reperfused myocardium was attenuated by 54% in the CD18 −/− mice and by 32% in ICAM-1 −/− mice compared with wild-type hearts. Deficiency in either CD18 or ICAM-1 expression results in a marked reduction in PMN accumulation and myocardial necrosis after acute MI/R.

scholarly journals The Outcome of Renal Ischemia-Reperfusion Injury Is Unchanged in AMPK-β1 Deficient Mice

PLoS ONE ◽  
2012 ◽  
Vol 7 (1) ◽  
pp. e29887 ◽  
Author(s):  
Peter F. Mount ◽  
Kurt Gleich ◽  
Shanna Tam ◽  
Scott A. Fraser ◽  
Suet-Wan Choy ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Renal Ischemia Reperfusion Injury ◽  
Deficient Mice

scholarly journals Ischemia-reperfusion injury is attenuated in VAP-1-deficient mice and by VAP-1 inhibitors

2008 ◽  
Vol 38 (11) ◽  
pp. 3041-3049 ◽  
Author(s):  
Jan Kiss ◽  
Sirpa Jalkanen ◽  
Ferenc Fülöp ◽  
Timo Savunen ◽  
Marko Salmi
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Deficient Mice

Abstract 213: Rapid Activation of G-Protein Coupled Estrogen Receptor 1 Protects the Heart Against Ischemia-Reperfusion Injury by Inhibiting the mPTP Opening via PKC/AKT/ERK/GSK-3b Pathways

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Jean Chrisostome Bopassa ◽  
Rong Lu ◽  
Harpreet Singh ◽  
Netanel F Zilberstein ◽  
Bjorn Olde ◽  
...  
Keyword(s):  
Infarct Size ◽  
G Protein ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Wild Type ◽  
Mptp Opening ◽  
Estrogen Effects ◽  
Estrogen Effect ◽  
Rapid Activation ◽  
G Protein Coupled

Introduction: Estrogen effect can be mediated by three receptors: Classical estrogen receptors: alpha (ERa) and beta (ERb), and recently identified G protein-coupled estrogen receptor1 (GPER1). Hypothesis: We investigated the role of ERa, ERb and GPER1 in mediating rapid estrogen-induced cardioprotection in male mice hearts subjected to ischemia/reperfusion using wild type (WT) and gene specific knockout animals. Methods: Isolated hearts from wild type (WT: C57BL/6NCrL), ERa-/-, ERb-/- and GPER1-/- were perfused using Langendorff apparatus with Krebs Henseleit buffer (control) or with the addition of estrogen (40 nM). Hearts were subjected to 18 min global ischemia followed by 60 min reperfusion. Cardiac function was recorded during the entire experiment and myocardial infarct size measured by TTC staining at the end of the reperfusion. Mitochondria calcium retention capacity (CRC) required to induce the mitochondrial permeability transition pore (mPTP) opening was assessed after 10 min reperfusion. Protein levels were measured by Western Blot in whole heart lysates after 5 min treatment just before ischemia, and after 10 min reperfusion. LY294002, U0126 and Chelerythrin-Cl were used as inhibitor of PI-3K/Akt, MAPK/ERK and PKC translocation, respectively. Results: In WT, ERa-/- and ERb-/-, estrogen treatment significantly improved cardiac functional recovery, reduced infarct size and improved mitochondrial CRC. However, estrogen effects were completely absent in GPER1-/-. Estrogen treatment during 5 min before ischemia induced up-regulation of Akt, GSK-3b, and ERK1/2 phosphorylation in WT mouse as compared with control but not in GPER1-/-. However, after 10 min reperfusion estrogen effect was still oserved on GSK-3b, but not on Akt and ERK1/2. Chelerythrin-Cl prevented estrogen-induced cardioprotection effect and U126 abolished estrogen effect on mitochondrial CRC while LY294002 could not prevent estrogen effect on GSK-3b observed in WT. P<0.05 and n=3-6. Conclusion: Rapid activation of GPER1 induces cardioprotection effect against ischemia/reperfusion injury. Estrogen effects through GPER1 are associated with phosphorylation of Akt, GSK-3b and ERK1/2, translocation of PKC, and inhibition of the mPTP opening.

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