Increased Lactate Dehydrogenase Levels Research Articles

Effect of Food Load on Activities of Enzymes of the Main Metabolic Pathways in Blood Lymphocytes in Girls with Different Anthropometric Parameters.

Changes in enzyme activities reflecting functioning of the basic metabolic pathways in cells (Krebs cycle, glycolysis, pentose phosphate pathway) were evaluated in blood lymphocytes of girls of different somatotypes with different body composition under conditions of food load. A common regularity was found: a decrease in succinate dehydrogenase activity after meal in girls of all somatotypes. Specific features of individual somatotypes were also revealed. Only girls of athletic somatotype showed increased lactate dehydrogenase level after food load. Activity of glucose-6-phosphate dehydrogenase increased (more than twice) after food load only in girls of euryplastic somatotype. This somatotype is characterized by maximum values of fat and other components of the body. Glucose-6-phosphate dehydrogenase is the first enzyme of the pentose phosphate pathway; activation of this pathway accompanies enhancement of synthetic processes, including lipid synthesis. This can contribute to accumulation of the fat component (and other components) due to redistribution of substrate flows between metabolic pathways.

A novel nicotinic mechanism underlies β-amyloid-induced neurotoxicity

Loss of basal forebrain cholinergic neurons (BFCN) correlates with cognitive deficits in Alzheimer disease (AD). Our recent evidence suggests that chronic exposure to Aβ up-regulated neuronal α7-nAChRs and increased neuronal excitability in cultured hippocampal neurons. However, the impact of the up-regulated α7-nAChRs on Aβ-induced neurotoxicity remains unclear. In this study, we investigated the role of α7-nAChRs in the mediation of Aβ-induced neurotoxicity. The effects of Aβ exposure on α7-nAChRs and cytotoxicity were examined using whole-cell patch clamp recordings, atomic force microscope (AFM) imaging, immunoprecipitation, and lactate dehydrogenase (LDH) release assay in primary cultured hippocampal neurons as well as differentiated human neuroblastoma (SH-SY5Y) cells with cholinergic characteristics. We found that α7-nAChRs are necessary for Aβ-induced neurotoxicity in hippocampal neurons because chronic Aβ significantly increased LDH level in hippocampal cultures, which was prevented by either α7-nAChR antagonist methyllycaconitine (MLA) or by α7 subunit gene deletion (cultures prepared from nAChR α7 subunit KO mice), whereas β2-containing nAChR antagonist (dihydro-β-erythroidine, DhβE) or the genetic deletion of nAChR β2 subunit (cultures prepared from β2 KO mice) failed to prevent Aβ-induced toxicity. In SH-SY5Y cells, larger aggregates of Aβ preferentially up-regulated α7-nAChR expression and function accompanied by a significant decrease in cell viability. Co-treatment MLA, but not mecamylamine (MEC), prevented Aβ exposure-induced neurotoxicity. Our results suggest a detrimental role of upregulated α7-nAChRs in the mediation of Aβ-induced neurotoxicity.

Significance of CSF-LDH in various types of meningitis

The cerebrospinal fluid concentration of Lactate dehydrogenase (LDH) was studied in patients with pyogenic and tubercular meningitis. Significant increase in LDH level (P<0.001) were observed in the test group when compared to the control group. LDH may useful in differentiating viral from other meningitis. It may act as corroborative evidence of meningitis.

Role of Sulf2 in Alveolar Epithelial Injury and Repair

Alveolar epithelial cell injury and dysfunction have been proposed to be etiopathogenic factors in the development of idiopathic pulmonary fibrosis (IPF). We have shown previously that heparan sulfate (HS) 6-O-endosulfatase 2 (Sulf2) is overexpressed and specifically localized to the hyperplastic type II alveolar epithelial cells (AECs) in IPF lungs. By removing 6-O-sulfates from specific HS intrachain sites, Sulf2 has been shown to modulate the functions of many growth factors and cytokines including the fibroblast growth factors (FGFs), Wnt ligands, and transforming growth factor (TGF)-β1. We hypothesize in this study that Sulf2 plays a regulatory role in alveolar epithelial injury and repair in the development of IPF. We examined Sulf2 expression and localization in the bleomycin injury/fibrosis model in mice, using quantitative real-time PCR and immunohistochemistry. Consistent with the findings from human IPF lungs, bleomycin treatment in mice resulted in a twofold increase in Sulf2 mRNA expression in whole lung extracts, and Sulf2 protein was localized to the type II AECs, using immunohistochemistry on lung sections. In cultured primary murine type II AECs, bleomycin induced Sulf2 expression at both the mRNA and protein levels. To study the role of Sulf2 in alveolar epithelial injury and repair in vivo, we generated a doxycycline-inducible type II AEC-specific Sulf knockout mouse line. Deletion of Sulf2 was confirmed in freshly isolated type II AECs from these mice after doxycycline administration. We compared bleomycin-induced AEC injury in wild-type and type II AEC–specific Sulf knockout mice. Our results suggest that deletion of Sulf2 in type II AECs exacerbated bleomycin-induced epithelial injury as shown by increased lactate dehydrogenase levels in bronchoalveolar lavage fluid and increased epithelial apoptosis in type II AEC-Sulf knockout mice. We conclude from this study that Sulf2 promotes type II AEC survival after alveolar epithelial injury.

Risk factors of recurrence among 471 Chinese patients with Budd-Chiari syndrome

Budd-Chiari syndrome (BCS) is a rare form of vascular disease. There is limited literature available regarding the prognosis of this disease. The aim of this study was to characterize the cumulative recurrence rates and to investigate the risk factors of recurrence in Chinese patients with BCS. Four hundred and seventy-one patients were diagnosed as having BCS in the Affiliated Hospital of Xuzhou Medical College (Jiangsu, China) between January 2008 and December 2012. Follow-ups were conducted by phone calls or correspondence. Cumulative recurrence rates were assessed with the Kaplan-Meier curves. Independent risk factors of recurrence were calculated with the Cox's proportional hazards regression model. Four hundred and twenty-five patients with BCS had complete follow-up data, in which 24 patients died, 98 patients had recurrence, with the median duration of follow-up being 19.3 months (range 3 to 61.4). The cumulative 1-, 2-, 3-, 4- and 5-year recurrence rates were 12%, 22%, 27%, 35% and 42%, respectively. Univariable and multivariable Cox's proportional hazards regression models showed that the risk factors of recurrence include: age ≤ 30 years (HR=2.261, 95% CI: 1.412-3.621), differentiated typology (hepatic vein type: HR=1.885, 95% CI: 1.045-3.402; combined type: HR=2.088, 95% CI: 1.233-3.536), elevated lactate dehydrogenase (LDH) levels (HR=1.125, 95% CI: 1.101-1.212) and the Child-Pugh class B/C (B: HR=1.758, 95% CI: 1.057-2.926; C: HR=2.626, 95% CI: 1.396-4.940). Regardless of thrombophilia and haematological causes, exceptionally found in Chinese patients, the 5-year recurrence rate of BCS was as high as 42%. Age ≤ 30 years, hepatic vein type, combined type, increased LDH levels and the Child-Pugh class B/C were independent predictors of BCS recurrence.

Adverse effects of immunoglobulin G therapy: thromboembolism and haemolysis.

Adverse effects of immunoglobulin G therapy: thromboembolism and haemolysis.

Risk factors for pancreatic infection in patients with severe acute pancreatitis: An analysis of 163 cases

We aimed to identify the risk factors for predicting pancreatic infection in patients with severe acute pancreatitis (SAP). In all, 163 patients with SAP were included and divided into two groups based on the presence or absence of pancreatic infection. Their demographic and clinical characteristics, laboratory examination results, complications and treatment modalities were collected from their medical records. Variables were initially screened by univariate analysis and those with statistical significance were then filtered by multivariate analysis to determine the independent risk factors for pancreatic infection in SAP. Patients having SAP with pancreatic infection had a lower partial pressure of arterial carbon dioxide (PaCO2 ), peripheral white blood cell count and alkaline phosphatase levels, together with a higher computed tomography severity index (CTSI) than those without pancreatic infection, while their lactate dehydrogenase (LDH) levels and blood urea nitrogen were much higher. Pancreatic infection was also more common in patients receiving late fluid resuscitation than in those receiving early fluid resuscitation. Multivariate analyses revealed that increased LDH level, high CTSI, delayed fluid resuscitation and hypoxemia were independent risk factors for pancreatic infection in SAP. The sensitivity, specificity, positive and negative predictive values for a model combining the parameters in predicting pancreatic infection were 84%, 97%, 88% and 96%, respectively, with a cut-off value of 0.393, and the area under the receiver operating characteristic curve was 0.923. Increased LDH, high CTSI, delayed fluid resuscitation and hypoxemia are independent risk factors for predicting pancreatic infection in patients with SAP.

Existence of glia mitigated ketamine-induced neurotoxicity in neuron–glia mixed cultures of neonatal rat cortex and the glia-mediated protective effect of 2-PMPA

The present study compared ketamine-induced neurotoxicity in the neuron–glia mixed cultures and neuronal cultures and further explored the neuroprotective effect of the NAAG peptidase inhibitor 2-(phosphonomethyl) pentanedioic acid (2-PMPA). Firstly, Rosenfeld's staining and immunofluorescence staining of microtubule-associated protein 2 (MAP2) and glial fibrillary acidic protein (GFAP) were used to address the difference of morphology in the mixed cultures and neuronal cultures. Our results showed that neurons and astrocytes grew in good conditions. The ratio of neurons and astrocytes in the mixed cultures was around 1:1, and the purity of neurons in the neuronal cultures is 91.3%. Furthermore, ketamine was used to test the hypothesis that the presence of a higher proportion of glia in the mixed cultures would be protective against ketamine-induced neurotoxicity in the mixed cultures compared with neuronal cultures. The results showed that ketamine-induced morphological changes, cell viability decrease and lactate dehydrogenase (LDH) levels increase were significantly mitigated in neuron–glia mixed cultures compared with neuronal cultures. Furthermore, 2-PMPA was included to further explore efficient protective drug for ketamine-induced neurotoxicity. Our results showed that 2-PMPA reduced ketamine-induced decrease of cell viability and increase of LDH levels in the mixed cultures but not in the neuronal cultures. Further morphological changes of neurons and astrocytes also indicated that 2-PMPA could improve ketamine damaged neurons in the mixed cultures instead of neuronal cultures. These results indicate that glia protect neurons from ketamine-induced neurotoxicity. These data further suggest that glia mediate the neuroprotective effect of 2-PMPA and 2-PMPA has the potential to treat ketamine-induced neurotoxicity in vivo. Delineating the mechanisms underlying the communication between neurons and glia and the neuroprotective effects of 2-PMPA in the mixed cultures to ketamine-induced neurotoxicity require further investigation.

Culture media from hypoxia conditioned endothelial cells protect human intestinal cells from hypoxia/reoxygenation injury

Remote ischemic preconditioning (RIPC) is a phenomenon, whereby short episodes of non-lethal ischemia to an organ or tissue exert protection against ischemia/reperfusion injury in a distant organ. However, there is still an apparent lack of knowledge concerning the RIPC-mediated mechanisms within the target organ and the released factors. Here we established a human cell culture model to investigate cellular and molecular effects of RIPC and to identify factors responsible for RIPC-mediated intestinal protection.Human umbilical vein cells (HUVEC) were exposed to repeated episodes of hypoxia (3×15min) and conditioned culture media (CM) were collected after 24h. Human intestinal cells (CaCo-2) were cultured with or without CM and subjected to 90min of hypoxia/reoxygenation injury. Reverse transcription-polymerase chain reaction, Western blotting, gelatin zymography, hydrogen peroxide measurements and lactate dehydrogenase (LDH) assays were performed.In HUVEC cultures hypoxic conditioning did not influence the profile of secreted proteins but led to an increased gelatinase activity (P<0.05) in CM. In CaCo-2 cultures 90min of hypoxia/reoxygenation resulted in morphological signs of cell damage, increased LDH levels (P<0.001) and elevated levels of hydrogen peroxide (P<0.01). Incubation of CaCo-2 cells with CM reduced the hypoxia-induced signs of cell damage and LDH release (P<0.01) and abrogated the hypoxia-induced increase of hydrogen peroxide. These events were associated with an enhanced phosphorylation status of the prosurvival kinase Erk1/2 (P<0.05) but not Akt and STAT-5.Taken together, CM of hypoxia conditioned endothelial cells protect human intestinal cells from hypoxia/reoxygenation injury. The established culture model may help to unravel RIPC-mediated cellular events and to identify molecules released by RIPC.

Usefulness of magnetic resonance imaging as a prognostic variable in myelodysplastic syndromes.

BackgroundMyelodysplastic syndromes are clonal disorders of stem cells, characterized by heterogeneous clinical presentation. Hematopoiesis is ineffective, characterized by abnormal differentiation, maturation and survival of hematopoietic cells.Material/MethodsThe examinations were conducted in the Hematology Ward and the Internal Medicine Ward of the Specialist Hospital No. 1 in Bytom in the years 2006–2011. The study group included 53 patients with diagnosed myelodysplastic syndrome. The results of magnetic resonance imaging (MRI) of the spine were obtained from the medical documentation of patients.ResultsIn the group of patients diagnosed with RT (refractory thrombocytopenia) and in the group diagnosed with RA (refractory anemia), 100% of lumbar spine images in T1- and T2-weighted sequences assessed together showed increased signal intensity. In patients diagnosed with RAEB (refractory anemia with excess blasts), MRI showed decreased signal intensity in 76.5% of subjects in the sequences analyzed together. In the group of patients with increased LDH (lactate dehydrogenase), 22 patients (55%) showed decreased signal intensity in the combined analysis of T1- and T2-weighted sequences. Among transfusion-dependent patients, 20 scans (60.6%) showed decreased signal intensity.ConclusionsAs the risk category of MDS increases towards high – bad risk, decreased signal intensity is observed in lumbar spine MRI in T1- and T2-weighted images in all studied stratification scales. There is a positive correlation between decreased signal intensity in lumbar spine MRI examinations and increased LDH level in blood serum, as well as dependence on blood product transfusions, especially packed red blood cells.

The effect of erythropoietin on lactate dehydrogenase levels during ischemia-reperfusion injury in rats

Objective: Aim of this experimental study was to examine the effect of erythropoietin (Epo) on a rat model and particularly in tissues by an ischemia-reperfusion (IR) protocol. The beneficial effect or non-effectiveness of that molecule were studied biochemically using mean blood lactate dehydrogenase (LDH) as a parameter of tissues’ injury. Methods: Forty rats with a mean weight of 247.7 g were used in the study. LDH levels were measured 60 min (groups A and C) and 120 min (groups B and D) after reperfusion. Placebo drug was administered in sham operated group A and B, while Epo was administered in groups C and D. The predicted LDH values, adjusted for rats’ weight were calculated since there was a significant relation between rats’ weight and LDH levels (p= 0.0469). Results: Epo administration significantly increased the LDH levels by 778.3 IU/L [200.6627 IU/L - 1355.937 IU/L] (p= 0.0096). This finding was in accordance with the results of a paired t-test (p= 0.0004). Reperfusion time non-significantly decreased the LDH levels by 124.9 IU/L [-755.2258 IU/L - 505.4258 IU/L] (p= 0.6906), also in accordance with a paired t-test (p= 0.6354). Epo administration and reperfusion time together produced a significant combined effect of increasing LDH levels by 376.8 IU/L [16.55497 IU/L - 737.045 IU/L] (p= 0.0408). Conclusion : Results of this study indicate that Epo administration alone or in interaction with reperfusion time, has increasing short – term effects on LDH levels. These increases are significant for the original LDH values and non-significant for predicted values. Considering the predicted values as more reliable, it is concluded that Epo administration declines the postischemically raised LDH levels effectively, suggesting a greater-than-expected restorating role of Epo in tissues.

Decreased Hematocrit-To-Viscosity Ratio and Increased Lactate Dehydrogenase Level in Patients with Sickle Cell Anemia and Recurrent Leg Ulcers

Leg ulcer is a disabling complication in patients with sickle cell anemia (SCA) but the exact pathophysiological mechanisms are unknown. The aim of this study was to identify the hematological and hemorheological alterations associated with recurrent leg ulcers. Sixty-two SCA patients who never experienced leg ulcers (ULC-) and 13 SCA patients with a positive history of recurrent leg ulcers (ULC+) - but with no leg ulcers at the time of the study – were recruited. All patients were in steady state condition. Blood was sampled to perform hematological, biochemical (hemolytic markers) and hemorheological analyses (blood viscosity, red blood cell deformability and aggregation properties). The hematocrit-to-viscosity ratio (HVR), which reflects the red blood cell oxygen transport efficiency, was calculated for each subject. Patients from the ULC+ group were older than patients from the ULC- group. Anemia (red blood cell count, hematocrit and hemoglobin levels) was more pronounced in the ULC+ group. Lactate dehydrogenase level was higher in the ULC+ group than in the ULC- group. Neither blood viscosity, nor RBC aggregation properties differed between the two groups. HVR was lower and RBC deformability tended to be reduced in the ULC+ group. Our study confirmed increased hemolytic rate and anemia in SCA patients with leg ulcers recurrence. Furthermore, our data suggest that although systemic blood viscosity is not a major factor involved in the pathophysiology of this complication, decreased red blood cell oxygen transport efficiency (i.e., low hematocrit/viscosity ratio) may play a role.

The Inhibitory Effects of Phenolic and Terpenoid Compounds from Baccharis trimera in Siha Cells: Differences in Their Activity and Mechanism of Action

Baccharis trimera is used in folk medicine as a tea for digestive and liver diseases. It possesses anti-inflammatory and antioxidant properties that are related to the presence of phenolic compounds. The aim of this work was to investigate the anti-proliferative properties of phenolic (PHE) and terpenoid (SAP) compounds from B. trimera on human cervical cancer. The treatment of SiHa cells with PHE for 24 h suppressed colony formation in a dose-dependent manner, inhibited proliferation and inhibited cell motility. Although SAP inhibited the proliferation of SiHa cells in a dose-dependent manner, it increased colony formation and did not inhibit cell motility. PHE and SAP also promoted a significant increase in lactate dehydrogenase levels in the culture medium in a dose-dependent manner, indicating a loss of cell membrane integrity. Moreover, PHE promoted necrotic cell death, whereas SAP induced apoptosis. These compounds are new anticancer prototypes due their significant anticancer activity demonstrated herein.

Prognostic Role of Serum Lactate Dehydrogenase Beyond Initial Diagnosis: A Retrospective Analysis of Patients with Diffuse Large B Cell Lymphoma

Background/Aims: Baseline serum lactate dehydrogenase (LDH) level is a well-known prognostic factor in patients with non-Hodgkin's lymphoma; however, its role beyond initial diagnosis has not yet been defined. Methods: This study was conducted as a retrospective analysis of patients with diffuse large B cell lymphoma (DLBCL) treated with R-CHOP21, who had undergone regular checks for LDH during immunochemotherapy (n = 119) and during the posttreatment follow-up period after complete remission (CR; n = 100). The 119 patients were classified into 4 groups according to their baseline and change in LDH level during treatment, and an analysis of tumor response and survival was performed. The value of LDH as a predictor for relapse was evaluated among the patients with regular follow-up visits after achieving CR. Results: An increased LDH level during immunochemotherapy had no impact on tumor response or survival, and only the LDH status ‘before' treatment was a prognostic marker. The sensitivity, specificity, positive predictive value and negative predictive value of serum LDH for detecting relapse after CR were 47.4, 86.5, 9.3 and 98.3%, respectively. Conclusion: The measurement of LDH level beyond initial diagnosis has no clear benefit in predicting disease progression or relapse in patients with DLBCL treated with R-CHOP21.

Hydroquinone induces oxidative and mitochondrial damage to human retinal Müller cells (MIO-M1)

PurposeSmoking is a risk factor in the development of a variety of neuroretinal diseases. Therefore, we have investigated the effects of hydroquinone (HQ), a toxicant that is present in high concentrations in cigarette smoke, on a human retinal Müller cell line (MIO-M1). MethodsMIO-M1 cells were treated for 24h with four different concentrations of HQ (200μM, 100μM, 50μM, and 25μM). Assays were used to measure cell viability, reactive oxygen/nitrogen species (ROS/RNS), mitochondrial dehydrogenase activity (WST assay), caspase-3/7 activity and lactate dehydrogenase (LDH) levels. Western blot analyses with anti-LC3 and anti-GAPDH antibodies were performed on HQ-treated samples. Some cultures were treated with 4μM rapamycin, to induce autophagy, with and without the autophagy inhibitor 3-methyl-adenine (3MA), and levels of ROS/RNS and LDH were measured. ResultsOur findings show that HQ reduced cell viability at four different concentrations tested (200, 100, 50 and 25μM); decreased mitochondrial function at concentrations of 200 and 100μM; increased ROS/RNS activity at all the concentrations tested and increased LDH levels at concentrations of 200, 100 and 50μM. Caspase-3/7 activities were not modified by HQ. However, treatment of these cells with this agent resulted in the appearance of the autophagy associated LC3-II band. Pre-treatment with 3MA reduced the ROS/RNS and LDH levels of the HQ-treated and rapamycin-treated cells. ConclusionOur study suggests that HQ damages the MIO-M1 cells through oxidative, mitochondrial and autophagic pathways and not caspase-related apoptosis.

Progressive course of isolated splenic myeloid sarcoma

Abstract A previously healthy 40-year-old male presented with a 2-week history of fever and abdominal discomfort that was resistant to empirical broad-spectrum antibiotic treatment. The patient’s blood cell count and complete biochemical panel was normal, except for an increased lactate dehydrogenase level. Ultrasonography and computed tomography of the abdomen showed a large, soft tissue mass had infiltrated superior part of the spleen. Splenectomy with total tumor mass removal were performed. The pathological examination of the tumor tissue confirmed diagnosis of isolated myeloid sarcoma with monoblastic differentiation. Despite intensive antileukemic therapy, patient died four months after diagnosis was established.

Rhinacanthus nasutus Ameliorates Cytosolic and Mitochondrial Enzyme Levels in Streptozotocin-Induced Diabetic Rats.

The present study was conducted to evaluate the therapeutic efficacy of Rhinacanthus nasutus (R. nasutus) on mitochondrial and cytosolic enzymes in streptozotocin-induced diabetic rats. The rats were divided into five groups with 6 rats in each group. The methanolic extract of R. nasutus was orally administered at a dose of 200 mg/kg/day, and glibenclamide was administered at a dose of 50 mg/kg/day. All animals were treated for 30 days and were sacrificed. The activities of both intra- and extramitochondrial enzymes including glucose-6-phosphate dehydrogenase (G6PDH), succinate dehydrogenase (SDH), glutamate dehydrogenase (GDH), and lactate dehydrogenase (LDH) were measured in the livers of the animals. The levels of G6PDH, SDH, and GDH were significantly reduced in the diabetic rats but were significantly increased after 30 days of R. nasutus treatment. The increased LDH level in diabetic rats exhibited a significant reduction after treatment with R. nasutus. These results indicate that the administration of R. nasutus altered the activities of oxidative enzymes in a positive manner, indicating that R. nasutus improves mitochondrial energy production. Our data suggest that R. nasutus should be further explored for its role in the treatment of diabetes mellitus.

Subacute inhalation toxicity assessment of fly ash from industrial waste incinerators

Fly ash from industrial waste incinerators has been a significant concern because of their constituent toxic heavy metals and organic compounds. The objective of this study was to identify the subacute inhalation toxicity of fly ash from industrial waste incinerators, using whole body inhalation exposure chambers. Male and female groups of Sprague-Dawley rats were exposed to fly ash by inhalation of concentrations of 0, 50, 100, 200 mg/m3, for 6 h/day, 5 days/week for 4 weeks. There was no significant difference in body weight, and relative organ weight to body weight, between the exposure groups and the control group. Hematological examinations revealed a significant increase of monocyte counts in fly ash exposed rats and brown pigment laden macrophage was found in the lungs of rats exposed to high concentration of fly ash. A decrease of blood glucose levels and an increase in glutamate oxaloacetate transaminase activity were observed in fly ash treated rats. There was also a significant increase of lactate dehydrogenase levels in rat blood exposed fly ash. A significant dose-dependent increase of DNA damage was found in lymphocytes, spleen, bronchoalveolar lavage, liver, lung, and thymus of rats exposed to fly ash. In addition, the level of lipid peroxidation was increased in the plasma of rats exposed to a high concentration of fly ash. These results suggest that inhalation of fly ash from industrial waste incinerators can induce histopathologic, hematological, and serum biochemical changes and oxidative damage.

Warburg Effect’s Manifestation in Aggressive Pheochromocytomas and Paragangliomas: Insights from a Mouse Cell Model Applied to Human Tumor Tissue

A glycolytic profile unifies a group of pheochromocytomas and paragangliomas (PHEOs/PGLs) with distinct underlying gene defects, including von Hippel-Lindau (VHL) and succinate dehydrogenase B (SDHB) mutations. Nevertheless, their tumor aggressiveness is distinct: PHEOs/PGLs metastasize rarely in VHL-, but frequently in SDHB-patients. To date, the molecular mechanisms causing the more aggressive phenotype in SDHB-PHEOs/PGLs remain largely unknown. Recently, however, an excellent model to study aggressive PHEOs (mouse tumor tissue (MTT) cells) has been developed from mouse PHEO cells (MPC). We employed this model for a proteomics based approach to identify changes characteristic for tumor aggressiveness, which we then explored in a homogeneous set of human SDHB- and VHL-PHEOs/PGLs. The increase of glucose transporter 1 in VHL, and of hexokinase 2 in VHL and SDHB, confirmed their glycolytic profile. In agreement with the cell model and in support of decoupling of glycolysis, the Krebs cycle and oxidative phosphorylation (OXPHOS), SDHB tumors showed increased lactate dehydrogenase levels. In SDHB-PGLs OXPHOS complex activity was increased at complex III and, as expected, decreased at complex II. Moreover, protein and mRNA expression of all tested OXPHOS-related genes were higher in SDHB- than in VHL-derived tumors. Although there was no direct evidence for increased reactive oxygen species production, elevated superoxide dismutase 2 expression may reflect elevated oxidative stress in SDHB-derived PHEOs/PGLs. For the first time, we show that despite dysfunction in complex II and evidence for a glycolytic phenotype, the Warburg effect does not seem to fully apply to SDHB-PHEOs/PGLs with respect to decreased OXPHOS. In addition, we present evidence for increased LDHA and SOD2 expression in SDHB-PHEOs/PGLs, proteins that have been proposed as promising therapeutic targets in other cancers. This study provides new insight into pathogenic mechanisms in aggressive human PHEOs/PGLs, which may lead to identifying new diagnostic and prognostic markers in the near future.

Urotensin II protects ischemic reperfusion injury of hearts through ROS and antioxidant pathway

Urotensin II (UII) is a vasoactive peptide which is bound to a G protein-coupled receptor. UII and its receptor are upregulated in ischemic and chronic hypoxic myocardium, but the effect of UII on ischemic reperfusion (I/R) injury is still controversial. The aim of the present study was to investigate whether UII protects heart function against I/R injury. Global ischemia was performed using isolated perfused Langendorff hearts of Sprague–Dawley rats. Hearts were perfused with Krebs–Henseleit buffer for 20min pre-ischemic period followed by a 20min global ischemia and 50min reperfusion. Pretreatment with UII (10nM) for 10min increased recovery percentage of the post-ischemic left ventricular developed pressure and ±dp/dt, and decreased post-ischemic left ventricular end-diastolic pressure as compared with I/R group. UII decreased infarct size and an increased lactate dehydrogenase level during reperfusion. Cardioprotective effects of UII were attenuated by pretreatment with UII receptor antagonist. The hydrogen peroxide activity was increased in UII-treated heart before ischemia. The Mn-SOD, catalase, heme oxygenase-1 and Bcl-2 levels were increased, and the Bax and caspase-9 levels were decreased in UII-treated hearts. These results suggest that UII has cardioprotective effects against I/R injury partly through activating antioxidant enzymes and reactive oxygen species.