scholarly journals Impaired PI3K/Akt Signaling as a Potential Cause of Failure to Precondition Rat Hearts Under Conditions of Simulated Hyperglycemia

2015 ◽  
pp. 633-641 ◽  
Author(s):  
M. ZÁLEŠÁK ◽  
P. BLAŽÍČEK ◽  
I. GABLOVSKÝ ◽  
V. LEDVÉNYIOVÁ ◽  
M. BARTEKOVÁ ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
Tissue Samples ◽  
Acute Hyperglycemia ◽  
Protein Levels ◽  
Bax Protein ◽  
Rat Hearts ◽  
Cause Of Failure ◽  
The Impact

The aim of the study was to evaluate the impact of simulated acute hyperglycemia (HG) on PI3K/Akt signaling in preconditioned and non-preconditioned isolated rat hearts perfused with Krebs-Henseleit solution containing normal (11 mmol/l) or elevated (22 mmol/l) glucose subjected to ischemia-reperfusion. Ischemic preconditioning (IP) was induced by two 5-min cycles of coronary occlusion followed by 5-min reperfusion. Protein levels of Akt, phosphorylated (activated) Akt (P-Akt), as well as contents of BAX protein were assayed (Western blotting) in cytosolic fraction of myocardial tissue samples taken prior to and after 30-min global ischemia and 40-min reperfusion. In “normoglycemic” conditions (NG), IP significantly increased P-Akt at the end of long-term ischemia, while reperfusion led to its decrease together with the decline of BAX levels as compared to non-preconditioned hearts. On the contrary, under HG conditions, P-Akt tended to decline in IP-hearts after long-term ischemia, and it was significantly higher after reperfusion than in non-preconditioned controls. No significant influence of IP on BAX levels at the end of I/R was observed under HG conditions. It seems that high glucose may influence IP-induced activation of Akt and its downstream targets, as well as maintain persistent Akt activity that may be detrimental for the heart under above conditions.

scholarly journals FTY720 Effects on Inflammation and Liver Damage in a Rat Model of Renal Ischemia-Reperfusion Injury

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Anthony D. Foster ◽  
Diego Vicente ◽  
Nicholas Clark ◽  
Crystal Leonhardt ◽  
Eric A. Elster ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Treatment Strategies ◽  
Serum Markers ◽  
Organ Injury ◽  
Gene Transcript ◽  
Sprague Dawley ◽  
Tissue Samples ◽  
The Impact

Objective. Ischemia-reperfusion injury (IRI) produces systemic inflammation with the potential for causing organ failure in tissues peripheral to the initial site of injury. We speculate that treatment strategies that dampen inflammation may be therapeutically beneficial to either the initial site of injury or peripheral organs. To test this, we evaluated the impact of FTY720-induced sequestration of circulating mature lymphocytes on renal IRI and secondary organ injury. Methods. A microvascular clamp was surgically placed around the left renal pedicle of anesthetized male Sprague-Dawley rats with either vehicle or FTY720 treatment (0.3 mg/kg) intravenously injected after 15 min of ischemia. Blood flow was restored after 60 min. Cohorts of anesthetized rats were euthanized at 6, 24, or 72 hrs with tissue samples collected for analysis. Results. FTY720 treatment resulted in profound T lymphocyte reduction in peripheral blood. Histopathologic examination, clinical chemistries, and gene transcript expression measurements revealed that FTY720 treatment reduced hepatocellular degeneration, reduced serum markers of liver injury (ALT/AST), and reduced the expression of gene targets associated with IRI. Conclusion. These findings support an anti-inflammatory effect of FTY720 in the liver where the expression of genes associated with apoptosis, chemotaxis, and the AP-1 transcription factor was reduced. Findings presented here provide the basis for future studies evaluating FTY720 as a potential therapeutic agent to treat complications resulting from renal IRI.

scholarly journals Prognostic Value of the Acute-to-Chronic Glycemic Ratio at Admission in Heart Failure: A Prospective Study

2021 ◽  
Vol 11 (1) ◽  
pp. 6
Author(s):  
Mª José Carrera ◽  
Pedro Moliner ◽  
Gemma Llauradó ◽  
Cristina Enjuanes ◽  
Laura Conangla ◽  
...  
Keyword(s):  
Heart Failure ◽  
Multivariable Analysis ◽  
Acute Hyperglycemia ◽  
Glucose Levels ◽  
Long Term Prognosis ◽  
Shape Curve ◽  
A Prospective Study ◽  
The Impact ◽  
The Relationship

Acute hyperglycemia has been associated with worse prognosis in patients hospitalized for heart failure (HF). Nevertheless, studies evaluating the impact of glycemic control on long-term prognosis have shown conflicting results. Our aim was to assess the relationship between acute-to-chronic (A/C) glycemic ratio and 4-year mortality in a cohort of subjects hospitalized for acute HF. A total of 1062 subjects were consecutively included. We measured glycaemia at admission and estimated average chronic glucose levels and the A/C glycemic ratio were calculated. Subjects were stratified into groups according to the A/C glycemic ratio tertiles. The primary endpoint was 4-year mortality. Subjects with diabetes had higher risk for mortality compared to those without (HR 1.35 [95% CI: 1.10–1.65]; p = 0.004). A U-shape curve association was found between glucose at admission and mortality, with a HR of 1.60 [95% CI: 1.22–2.11]; p = 0.001, and a HR of 1.29 [95% CI: 0.97–1.70]; p = 0.078 for the first and the third tertile, respectively, in subjects with diabetes. Additionally, the A/C glycemic ratio was negatively associated with mortality (HR 0.76 [95% CI: 0.58–0.99]; p = 0.046 and HR 0.68 [95% CI: 0.52–0.89]; p = 0.005 for the second and third tertile, respectively). In multivariable analysis, the A/C glycemic ratio remained an independent predictor. In conclusion, in subjects hospitalized for acute HF, the A/C glycemic ratio is significantly associated with mortality, improving the ability to predict mortality compared with glucose levels at admission or average chronic glucose concentrations, especially in subjects with diabetes.

scholarly journals Examination of Bcl-2 and Bax Protein Levels for Determining the Apoptotic Changes in Placentas with Gestational Diabetes and Preeclampsia

Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1548 ◽  
Author(s):  
Ebru Gokalp-Ozkorkmaz ◽  
Firat Asir ◽  
Sureyya Ozdemir Basaran ◽  
Elif Agacayak ◽  
Firat Sahin ◽  
...  
Keyword(s):  
Gestational Diabetes ◽  
Positive Reaction ◽  
Placental Tissue ◽  
Tissue Samples ◽  
Protein Levels ◽  
Bax Protein ◽  
Protein Expressions ◽  
Human Placental Tissue ◽  
Apoptotic Activity ◽  
Immunohistochemical Techniques

Anti-apoptotic Bcl-2 and proapoptotic Bax genes are the most significant genes that are involved in the regulation of apoptosis. Abnormal apoptotic activity in preeclampsia and gestational diabetes is caused by dysregulation of these genes. In this study; we examined Bcl-2 and Bax protein expressions using immunohistochemical techniques in human placental tissue samples from cases of gestational diabetes (n: 20) and preeclampsia (n: 20). It was observed that Bax expression showed positive reaction compared to Bcl-2 expression so; Bax protein was thought to be an effective marker in determining apoptotic changes in placentas with gestational diabetes and preeclampsia.

scholarly journals Ischemic preconditioning attenuates mitochondrial localization of PTEN induced by ischemia-reperfusion

2011 ◽  
Vol 300 (6) ◽  
pp. H2177-H2186 ◽  
Author(s):  
Lingyun Zu ◽  
Xiaoxu Zheng ◽  
Bing Wang ◽  
Nirmal Parajuli ◽  
Charles Steenbergen ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Underlying Mechanism ◽  
Myocardial Infarct Size ◽  
Mitochondrial Localization ◽  
Pten Protein ◽  
Adenoviral Gene Transfer ◽  
Protein Levels ◽  
Bax Protein

Although the induction of myocyte apoptosis by ischemia-reperfusion (I/R) is attenuated by ischemic preconditioning (IPC), the underlying mechanism is not fully understood. Phosphatase and tensin homologs deleted on chromosome 10 (PTEN) promotes apoptosis through Akt-dependent and -independent mechanisms. We tested the hypothesis that IPC attenuates the mitochondrial localization of PTEN in the myocardium induced by I/R. Isolated hearts from wild-type mice were exposed to IPC or normal perfusion followed by 30 min of ischemia and reperfusion. IPC attenuated myocardial infarct size and apoptosis after I/R. Heart fractionation showed that mitochondrial PTEN and Bax protein levels and the physical association between them were increased by 30 min of I/R and that IPC attenuated all of these effects of I/R. Muscle-specific PTEN knockout decreased mitochondrial Bax protein levels in the reperfused myocardium and increased cell survival. To determine whether PTEN relocalization to mitochondria was influenced by I/R-induced production of ROS, hearts were perfused with N-acetylcysteine (NAC) to scavenge ROS or H2O2 to mimic I/R-induced ROS. Mitochondrial PTEN protein levels were decreased by NAC and increased by H2O2. PTEN protein overexpression was generated in mouse hearts by adenoviral gene transfer. PTEN overexpression increased mitochondrial PTEN and Bax protein levels and ROS production, whereas muscle-specific PTEN knockout produced the opposite effects. In conclusion, myocardial I/R causes PTEN localization to the mitochondria, related to the generation of ROS; IPC attenuates the mitochondrial localization of PTEN after I/R, potentially inhibiting the translocation of Bax to the mitochondria and resulting in improved cell viability.

scholarly journals Netrin-1 and kidney injury. I. Netrin-1 protects against ischemia-reperfusion injury of the kidney

2008 ◽  
Vol 294 (4) ◽  
pp. F739-F747 ◽  
Author(s):  
Weiwei Wang ◽  
W. Brian Reeves ◽  
Ganesan Ramesh
Keyword(s):  
Cell Activation ◽  
Ischemia Reperfusion Injury ◽  
Vascular Endothelial Cells ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tubular Damage ◽  
Endothelial Cell Activation ◽  
Protein Levels ◽  
Peritubular Capillaries ◽  
The Impact

Endogenous mechanisms exist to limit inflammation. One such molecule is netrin. This study examined the impact of ischemia-reperfusion (I/R) on netrin expression and the role of netrin in preventing renal inflammation and injury. All three isoforms of netrin (1, 3, and 4) are expressed in normal kidney. I/R significantly downregulated netrin-1 and -4 mRNA expression, whereas expression of netrin-3 was moderately upregulated at 24 h of reperfusion. The netrin receptor UNC5B mRNA increased at 3 h and but decreased at later time points. Expression of a second netrin receptor, DCC, was not altered significantly. I/R was associated with dramatic changes in netrin-1 protein abundance and localization. Netrin-1 protein levels increased between 3 and 24 h after reperfusion. Immunolocalization showed an interstitial distribution of netrin-1 in sham-operated kidneys which colocalized with Von Willebrand Factor suggesting the presence of netrin-1 in peritubular capillaries. After I/R, interstitial netrin-1 expression decreased and netrin-1 appeared in tubular epithelial cells. By 72 h after reperfusion, netrin-1 reappeared in the interstitium while tubular epithelial staining decreased significantly. Downregulation of netrin-1 in the interstitium corresponded with increased MCP-1 and IL-6 expression and infiltration of leukocytes into the reperfused kidney. Administration of recombinant netrin-1 significantly improved kidney function (blood urea nitrogen: 161 ± 7 vs. 104 ± 24 mg/dl, creatinine: 1.3 ± 0.07 vs. 0.75 ± 0.16 mg/dl, P < 0.05 at 24 h) and reduced tubular damage and leukocyte infiltration in the outer medulla. These results suggest that downregulation of netrin-1 in vascular endothelial cells may promote endothelial cell activation and infiltration of leukocytes into the kidney thereby enhancing tubular injury.

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