Lactate Dehydrogenase Isozymes Research Articles

Acclimation to warm temperatures modulates lactate and malate dehydrogenase isozymes in juvenile Horabagrus brachysoma (Günther)

Differential expression of isozymes enables fish to tolerate temperature fluctuations in their environment. The present study explores the modulation of lactate dehydrogenase (LDH) and cytoplasmic malate dehydrogenase (sMDH) isozyme expression in the heart, muscle, brain, liver, gill, and kidney of juvenile Horabagrus brachysoma after 30 days of acclimation at 26, 31, 33, and 36°C. LDH and sMDH zymography were performed using native polyacrylamide gel electrophoresis. The zymography revealed five distinct bands of LDH isoenzymes (labelled from cathode to anode as LDH-A4, LDH-A3B1, LDH-A2B2, LDH-A1B3, and LDH-B4) and three distinct bands of sMDH isoenzymes (labelled from cathode to anode as sMDH-A2, sMDH-AB, and sMDH-B2), with considerable variation in their expression in the tissues. Acclimation to the test temperatures did not influence the expression patterns of LDH or sMDH isozymes. Densitometric analysis of individual isozyme bands revealed a reduction in the densities of bands containing the LDH-B and sMDH-B molecules, while the densities of bands containing the LDH-A and sMDH-A molecules increased in the gills and muscle, indicating the role of these organs in adaptive responses to thermal acclimation. However, the total densities of the LDH and sMDH isozymes increased with higher acclimation temperatures, indicating that adaptation to increased temperatures in H. brachysoma is primarily characterised by quantitative changes in isozyme expression.

Promotion of NAD+ recycling by the hypoxia-induced shift in the lactate dehydrogenase isozyme profile reduces the senescence of human bone marrow-derived endothelial progenitor cells

Expansion of bone marrow-derived endothelial progenitor cells (EPCs) in vitro to obtain required cell numbers for therapeutic applications faces the challenge of growing cell senescence under the traditional normoxic culture condition. We previously found that 1% O2 hypoxic culture condition is favorable for reducing senescence of EPCs, but the mechanisms underlying the favorability are still unclear. Here, we found that, compared with normoxia, hypoxia induced a shift in lactate dehydrogenase (LDH) isozyme profile, which manifested as decreased LDH2 and LDH1 and increased LDH5, LDH4 and total LDHs. Moreover, under hypoxia, EPCs presented higher LDH activity, which could promote the conversion of pyruvate to lactate, as well as a higher level of NAD+, Bcl2 interacting protein 3 (BNIP3) expression and mitophagy. Additionally, under hypoxia, knock-down of the LDHA subunit increased the LDH2 and LDH1 levels and knock-down of the LDHB subunit increased the LDH5 level, while the simultaneous knock-down of LDHA and LDHB reduced total LDHs and NAD+ level. Inhibition of NAD+ recycling reduced BNIP3 expression and mitophagy and promoted cell senescence. Taken together, these data demonstrated that 1% O2 hypoxia induces a shift in the LDH isozyme profile, promotes NAD+ recycling, increases BNIP3 expression and mitophagy, and reduces EPC senescence. Our findings contribute to a better understanding of the connection between hypoxic culture conditions and the senescence of bone marrow-derived EPCs and provide a novel strategy to improve in vitro expansion of EPCs.

Association of serum lactate dehydrogenase (LDH) isozyme with prognosis of patients with metastatic clear cell renal cell carcinoma (mCRCC).

709 Background: LDH isozyme is a tetramer of two subunits, H chain and M chain, and is present in all living tissue. Five types of molecular forms characterize the LDH pattern, and tumor tissues relatively consist LDH-4 and LDH-5, composed with a high ratio of the M chain, compared to normal tissues. This study analyzed the association between LDH isozyme and prognosis of mCRCC after nephrectomy. Methods: Clinical records of mCRCC patients those who were initially diagnosed M0 disease at Nippon Medical School between 2012 and 2016 were retrospectively reviewed. LDH isozyme values before operation and at time of metastasis were checked. Isozyme patterns were classified into 6 types, LDH 1-5 dominant and common type, according to the most composed molecular form. Results: Out of 38 patients, 33 patients (87%) were male, 5 patients (13%) were female. Median age was 65 years old (36-87). pT1 was seen in 3 cases, pT2 in 4, pT3 in 27, and pT4 in 4. Pathological grade 2 were 9 cases, G3 in 21, and G4 in 8. As for the IMDC risk, favourable was 2 cases (5%), intermediate in 26 (68%) and poor in 10 (26%). Median LDH was 163 IU/L (113-317), and isozyme dominant pattern were as follows: LDH-2 in 9 cases (24%), LDH-3 in 6 (16%), LDH-4 in 4, LDH-5 in 11. 8 cases were common type, and no cases showed LDH-1 dominant. Median time from surgery to recurrence was 10 months (1-104), median follow-up period after recurrence was 18 months (4-72). 16 deaths occurred. No significant correlation was seen between pre-operative LDH isozyme pattern and pathological grade or pT stage. Pre-operative LDH isozyme did not correlate with the time to recurrence (p=0.7420). The median OS for LDH-4 dominant at the time of metastasis was 10.9 months, significantly shorter than other isozyme types (P=0.0134). Conclusions: LDH-4 dominant isozyme pattern at the time of recurrence has a short OS, proposing as a prognostic predictor in mRCC.

Effect of acupuncture on the energy metabolism of dogs with intervertebral disk disease and cervical disk herniation: A pilot study

Thirteen dogs with intervertebral disk disease (IVDD) and 3 dogs with cervical disk herniation (CVDH) were examined to determine the effects of acupuncture on energy metabolism. Acupuncture points GV14, GV20-1, BL18, BL23, BL26, GB30, and ST36 were selected for IVDD, while GV14, GV20-1, GB20, and BL23 were selected for CVDH. All dogs except no.13 did not receive medication during acupuncture treatment. Acupuncture effects were evaluated based on the IVDD/CVDH evaluation scales in Oji 2015 and Tanaka and Nakayama 2015. Blood samples were taken before and 30 min after acupuncture treatment. Pyruvate and lactate concentrations, lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) activity, the MDH/LDH ratio (M/L ratio), and LDH isozyme electrophoretic patterns served as energy metabolism markers. In IVDD/CVDH dogs that showed improvements, plasma pyruvate concentrations significantly decreased, the M/L ratio increased, and the plasma LDH isozyme pattern changed from predominantly LDH5 to predominantly LDH1. These data suggest that local redox potential is improved and energy metabolism is increased in dogs with IVDD/CVDH after acupuncture treatment. Acupuncture treatments may activate the citric acid cycle and increase ATP production, followed by improvement of the disease. Future studies with a large sample size are needed to clarify this hypothesis.

Diagnostic significance of lactate dehydrogenase in measles virus reinfection cases.

Lactate dehydrogenase (LDH) levels in measles virus (MeV) reinfection cases for the diagnosis of measles have not been extensively studied. Thus, we evaluated the significance of serum LDH in the immune response of patients with MeV reinfection in comparison with those of patients with primary infection. Among 70 patients who tested positive for MeV-RNA, 42 with high MeV-specific IgG avidity (HA) were suspected as cases of reinfection and 28 with low MeV-specific IgG (LA) were suspected as cases of primary infection. The viral loads in the HA group were also lower than those in the LA group (P < 0.001). The titers of MeV-specific IgM and IgG in the HA group were significantly lower and higher, respectively, than those in the LA group (P < 0.001). The total LDH and LDH isozyme levels were elevated in the LA group compared with those in the HA group (P < 0.001). Through receiver operating characteristic curve analyses, we determined that the area under the curve of total LDH level was 0.87 (95% CI 0.74-1.00) and that the discriminatory accuracy was high for total LDH and all isozymes. By stepwise binary logistic regression analysis considering MeV-specific IgG avidity, we developed a model using IgG, IgM, and total LDH as explanatory variables, which was optimal for distinguishing the LA and HA groups (adjusted R2 = 0.773, P < 0.001). Thus, the serum LDH level in addition to IgM and IgG may be useful parameters for differentiating MeV reinfection from primary infection.

Changes in the blood lactate dehydrogenase measurements in canines and felines following the international standardization of the assay method.

Lactate dehydrogenase (LDH) in blood is measured using the Japanese Society of Clinical Chemistry (JSCC) method in Japan and the International Federation of Clinical Chemistry (IFCC) method in other countries. In human clinical practice, the IFCC method replaced the JSCC method due to international standardization. Moreover, veterinary LDH measurement will also eventually shift to the IFCC method. However, the relationship between the IFCC and JSCC methods for LDH in various animals and whether they can be equated or not have not yet been investigated. This study aimed to present the changes in measurements in canines and felines after switching to the IFCC method. The plasma LDH activity of canines (N=177) and felines (N=115), who visited a secondary care veterinary clinic, was measured using the JSCC and IFCC methods. The IFCC/JSCC ratio was <1.0 in 85% of canines and 88% of felines, indicating that the IFCC method tended to show lower values than the JSCC method, presumably because LDH5 is dominant among the LDH isozymes in canines and felines. The increase in the systematic errors of both assays was in the high value range, with some samples exceeding the error tolerance from near the upper end of the reference range. When switching to the IFCC method for LDH measurement in canines and felines, each institution should consider whether the reference range and clinical diagnostic values established by the JSCC method are appropriate for continued use.

Murburn precepts for lactic-acidosis, Cori cycle, and Warburg effect: Interactive dynamics of dehydrogenases, protons, and oxygen.

It is unresolved why lactate is transported to the liver for further utilization within the physiological purview of Cori cycle, when muscles have more lactate dehydrogenase (LDH) than liver. We point out that the answer lies in thermodynamics/equilibriums. While the utilization of NADH for the reduction of pyruvate to lactate can be mediated via the classical mechanism, the oxidation of lactate (with/without the uphill reduction of NAD+ ) necessitates alternative physiological approaches. The latter pathway occurs via interactive equilibriums involving the enzyme, protons and oxygen or diffusible reactive oxygen species (DROS). Since liver has high DROS, the murburn activity at LDH would enable the cellular system to tide over the unfavorable energy barriers of the forward reaction (~476 kJ/mol; earlier miscalculated as ~26 kJ/mole). Further, the new mechanism does not necessitate any "smart decision-making" or sophisticated control by/of proteins. The DROS-based murburn theory explains the invariant active-site structure of LDH isozymes and their multimeric nature. The theoretical insights, in silico evidence and analyses of literature herein also enrich our understanding of the underpinnings of "lactic acidosis" (lowering of physiological pH accompanied by lactate production), Warburg effect (increased lactate production at high pO2 by cancer cells) and approach for cancer therapy.

Cannabichromene and Δ9-Tetrahydrocannabinolic Acid Identified as Lactate Dehydrogenase-A Inhibitors by in Silico and in Vitro Screening.

Cannabis sativa contains >120 phytocannabinoids, but our understanding of these compounds is limited. Determining the molecular modes of action of the phytocannabinoids may assist in their therapeutic development. Ligand-based virtual screening was used to suggest novel protein targets for phytocannabinoids. The similarity ensemble approach, a virtual screening tool, was applied to target identification for the phytocannabinoids as a class and predicted a possible interaction with the lactate dehydrogenase (LDH) family of enzymes. In order to evaluate this in silico prediction, a panel of 18 phytocannabinoids was screened against two LDH isozymes (LDHA and LDHB) in vitro. Cannabichromene (CBC) and Δ9-tetrahydrocannabinolic acid (Δ9-THCA) inhibited LDHA via a noncompetitive mode of inhibition with respect to pyruvate, with Ki values of 8.5 and 6.5 μM, respectively. In silico modeling was then used to predict the binding site for CBC and Δ9-THCA. Both were proposed to bind within the nicotinamide pocket, overlapping the binding site of the cofactor NADH, which is consistent with the noncompetitive modes of inhibition. Stemming from our in silico screen, CBC and Δ9-THCA were identified as inhibitors of LDHA, a novel molecular target that may contribute to their therapeutic effects.

Cancer-Testis Antigen Lactate Dehydrogenase C4 in Human Cancers: Old and New Perspectives

Lactate dehydrogenase (LDH) isozymes are abundant in various mammalian tissue types and accountable for the interconversion of pyruvate and lactate during the last step of anaerobic glycolysis...

Serum hydroxybutyrate dehydrogenase as an early predictive marker of the severity of acute pancreatitis: a retrospective study

BackgroundTo investigate the value of serum hydroxybutyrate dehydrogenase (HBDH) level, an isozyme of lactate dehydrogenase, in evaluating the severity of acute pancreatitis (AP).MethodsPatients diagnosed with AP from January 2013 to December 2018 were included in this retrospective study. Patients were divided into the normal serum HBDH levels group (n-HBDH group) and the high serum HBDH levels group (h-HBDH group) according to the criteria HBDH ≥ 182 U/L after admission. The demographic parameters, laboratory data and the severity of AP in the two groups were compared. The receiver operating curve (ROC) was used to evaluate the efficacy of serum HBDH in predicting persistent organ failure and systemic inflammatory response syndrome (SIRS).ResultsA total of 260 AP patients were enrolled, including 176 cases in the n-HBDH group and 84 cases in the h-HBDH group. The incidence of SIRS and organ failure in the h-HBDH group were significantly higher than those in n-HBDH group (both P < 0.001). In addition, the HBDH level was significantly decreased in 110 patients who were re-measured after AP treatment. The serum HBDH levels were positively correlated with Atlanta classification, Ranson score, and BISAP score (all P < 0.05). ROC analysis showed that a serum HBDH cut-off point of 195.0 U/L had optimal predictive value for the development of persistent organ failure (AUC = 0.778) and 166.5 U/L for the development of SIRS (AUC = 0.724).ConclusionThe elevated serum HBDH in early stage of AP is closely related to the adverse prognosis of AP patients, which can be used as a potential early biomarker for predicting the severity of AP.

유산소운동이 당뇨쥐 해마의 신경세포 LDH 동위효소, MCT2 및 GLUT3 단백질 발현에 미치는 영향

In the present study, the effects of aerobic exercise on expression of Lactate dehydrogenase (LDH) isozymes, Monocarboxylate transporter2 (MCT2) and Glucose transporter3 (GLUT3) in hippocampal neuron of Streptozotocin (STZ)-induced diabetic rats. The experimental animals were divided into three groups (n=10 in each group): the normal control group (CON), the diabetes mellitus group (DM), the diabetes and exercise group(DM-Ex). Animals in the exercise group were submitted to daily exercise in the water pool during 4weeks. Native polyacrylamide gel electrophoresis analysis for the purification of LDH isozyme was performed. Western blotting and immunohistochemistry analysis for the expression of MCT2 and GLUT3 was performed. Here in this study, LDH A4 and LDH A3B in DM were predominantly expressed compared to DM-Ex (p<.05), and LDH AB3 and LDH B4 in DM-Ex were predominantly expressed compared to DM (p<.05). MCT2 activity of DM and DM-Ex were significantly lower than that of CON (p<.05). MCT2 activity of DM-Ex was significantly higher than that of DM (p<.05). GLUT3 activity of DM and DM-Ex were significantly lower than that of CON (p<.05). GLUT3 activity of DM-Ex was significantly higher than that of DM (p<.05). The results of the present study indicate that aerobic exercise affects the production of ATP using lactic acid and the activity of neurons by adapting to the energy metabolic demands of diabetes in the hippocampal neurons.

Nuliglucaemia Lucidae: Extreme Deprivation of Blood Glucose as Organic Context for Cancer Treatment with Antimetabolites

The present report describes our clinical findings regarding the use of high dose intravenous insulin in cancer patients, as a means to deplete the blood compartment of glucose molecules. The purpose of this intervention is to create a favorable physiological state for the competitive inhibition of several rate-limiting enzymes within cancer cells, with structural analogues that behave as antimetabolites. Regardless of their histological origin, virtually all solid tumors reported on to date (February 2020) are found to be hypercaptant in PET-CT scans following the intravenous injection of 2-¹⁸fluoro-deoxy-D-glucose. Most solid tumors display a hypermetabolic phenotype (SUVmax ≥ 3), with marked overexpression of glucose transporters (GLUTs) in the outer membrane of their anaplastic cells subpopulations. The fact that neoplastic cells also overexpress glycolytic, fermentative and glutaminolytic enzymes up to an order of magnitude relative to healthy cells further strengthens the argument for a competitive inhibition with antimetabolites. The rationale for a deep, systemic deprivation of glucose was suggested by classical enzymological work concerning competitive inhibition (the Woods principle), and our group has shown that a metabolic intervention with structural analogues of glucose and pyruvate is strongly enhanced by a systemic suppression of the natural substrates of hexokinase 2 (HK-2) and lactic dehydrogenase isozyme A (LDH-A), followed by the timely introduction of several non- metabolizable analogues. Sustained, deep hypoglycemia (&lt;10mg/dl) under physiological ketosis provides an advantageous context for antitumor treatment with structural analogues of glucose, pyruvate and glutamine. Data provided in this report demonstrates the feasibility and safety of the procedure.

ARNT-dependent CCR8 reprogrammed LDH isoform expression correlates with poor clinical outcomes of prostate cancer.

Lactate dehydrogenase isozyme (LDH) is a tetramer constituted of two isoforms, LDHA and LDHB, the expression of which is associated with cell metabolism and cancer progression. Our previous study reveals that CC-chemokine ligand-18 (CCL18) is involved in progression of prostate cancer (PCa).This study aims to investigate how CCL18 regulates LDH isoform expression, and therefore, contributes to PCa progression. The data revealed that the expression of LDHA was upregulated and LDHB was downregulated in PCa cells by CCL18 at both messenger RNA and protein levels. The depletion of CCR8 reduced the ability of CCL18 to promote the proliferation, migration, and lactate production of PCa cells. Depletion of a CCR8 regulated transcription factor, ARNT, significantly reduced the expression of LDHA. In addition, The Cancer Genome Atlas dataset analyses revealed a positive correlation between CCR8 and ARNT expression. Two dimension difference gel electrophoresis revealed that the LDHA/LDHB ratio was increased in the prostatic fluid of patients with PCa and PCa tissues. Furthermore, increased LDHA/LDHB ratio was associated with poor clinical outcomes of patients with PCa. Together, our results indicate that the CCR8 pathway programs LDH isoform expression in an ARNT dependent manner and that the ratio of LDHA/LDHB has the potential to serve as biomarkers for PCa diagnosis and prognosis.

Stability of Serum Lactate Dehydrogenase Activity and Isozyme Pattern in Cattle Based on Storage Time and Temperature

Stability of Serum Lactate Dehydrogenase Activity and Isozyme Pattern in Cattle Based on Storage Time and Temperature

Isozymes of malate-and lactate dehydrogenase of Astyanax bimaculatus as biomarkers of environmental impact

The activity of certain isozymes may serve as biomarkers of specific physiological conditions of living organisms. The present work aimed to evaluate malate dehydrogenase (MDH) and lactate dehydrogenase (LDH) isozymes from the hepatic, branchial and renal tissues of the fish Astyanax bimaculatus as biochemical markers of environmental changes in the Una River Basin (Taubaté, SP, Brazil). For this study, the specimens were collected in water bodies located in three sampling sites of the basin, called P1 (Itaim stream), P2 (a stream along the Remédios municipal road) and P3 (a small lake near the Dr. José Luiz Cembranelli municipal road). Physicochemical analysis of the water from these sites indicated that P1 was the less polluted site, P2 presented high levels of electrolytes in water, and P3 presented the worst water quality among the sampling sites. The isoenzymes were separated by native-PAGE and identified by their activity on the polyacrylamide gel. The results indicated that four isozymes of MDH occur in the liver of these fish, and the activities of MDH-1 and MDH-4 were detected only in fish from P2, suggesting that these isoforms have potential as biomarkers of the presence of high levels of electrolytes in water. In the kidney, MDH-1 was detected in fish from P2 and P3, but it was not detected in those from P1, suggesting that the presence of this isozyme may be a biomarker of low-quality water. The gill MDH and LDH isozyme profiles of all tissues examined showed some similarities between individuals from the three collection sites, indicating that they are not suitable as biomarkers of the environmental conditions of these sites.

Hydrogen sulfide attenuates hyperhomocysteinemia-induced mitochondrial dysfunctions in brain

Hyperhomocysteinemia (HHcy) has been implicated in the development of neurodegenerative conditions and mild cognitive disorders. Mitochondrial dysfunctions are the major mechanisms involved in homocysteine (Hcy)-induced neurotoxicity. Although, hydrogen sulfide has been reported as potent antioxidant, its effects on Hcy-induced mitochondrial dysfunctions have not been studied. Therefore, the present study has been designed to evaluate the protective effect of NaHS on Hcy-induced mitochondrial dysfunctions in brain. NaHS supplementation decreased reactive oxygen species and nitrite levels in the cortex and hippocampus of animals with HHcy. NaHS supplementation increased the activity of mitochondrial electron transport chain components; NADH dehydrogenase, cytochrome c oxidase and F0-F1 ATPase in the cortex and hippocampus of HHcy animals along with in-gel activity of complex I – complex V in the mitochondria isolated from the cortex and hippocampus of HHcy animals. Moreover, NaHS supplementation also increased the mitochondrial complex I, II and IV mediated oxygen consumption rate in Hcy treated mitochondria. NaHS administration prevented the Hcy-induced mitochondrial damage as suggested by the decreased mitochondrial swelling in the cortex and hippocampus of HHcy animals. NaHS supplementation decreased the activity of lactate dehydrogenase isozymes (1–5) in the brain regions of HHcy animals. The expression of protein kinase c δ was also decreased in the brain regions of HHcy animals following NaHS supplementation. This was accompanied by reduced activity of caspase-3 indicating anti-apoptotic effect of H2S. Taken together, the findings suggest that H2S supplementation ameliorates Hcy-induced oxidative stress and mitochondrial dysfunctions suggesting H2S releasing drugs may be a novel therapeutic approach to treat HHcy associated neurological disorders.

Simultaneous evaluation of diagnostic marker utility for enzootic bovine leukosis

BackgroundEnzootic bovine leukosis (EBL) is a disease of cattle caused by bovine leukemia virus (BLV). More than 60% of BLV-infected cattle remain subclinical and are thus referred to as aleukemic (AL) cattle. Approximately 30% of infected cattle show a relatively stable increase in the number of B lymphocytes; these cattle are termed persistent lymphocytosis (PL) cattle. A small percentage of infected cattle develop BLV-induced B cell lymphoma (EBL) and are called EBL cattle. Due to the increase in the number of BLV-infected cattle, the number of EBL cattle has featured a corresponding increase over recent years in Japan. Several diagnostic criteria for EBL (e.g., enlarged superficial lymph nodes, protrusion of the eye, increased peripheral blood lymphocyte, etc.) are used for on-farm diagnosis and antemortem tests at slaughterhouses. Since the slaughter of EBL cattle for human consumption is not allowed, on-farm detection of EBL cattle is important for reducing the economic loss incurred by farms. Therefore, establishing new diagnostic markers to improve the efficiency and accuracy of the antemortem detection of EBL cattle is a critical, unmet need. To simultaneously evaluate the utility of candidate markers, this study measured the values of each marker using the blood samples of 687 cattle with various clinical statuses of BLV infection (EBL, PL, AL and non-infected cattle).ResultsSensitivity (Se) and specificity (Sp) were highest for the serum thymidine kinase (TK) followed by the serum lactate dehydrogenase (LDH) isozyme 2. The number of peripheral blood lymphocytes and proviral load in peripheral blood had the lowest Se and Sp. The values of all markers other than TK were influenced by the sex of the tested cattle.ConclusionsAlthough tLDH and its isozymes (LDHs) may be influenced by the sex of the tested cattle, the high accuracy of TK and LDH2 as well as accessibility and simplicity of the protocol used to measure these enzymes recommend the utility of TK and LDHs for EBL cattle detection. Using these markers for screening followed by the application of existing diagnostic criteria may improve the efficiency and accuracy of EBL cattle detection on farms, thereby contributing to the reduction of economic losses in farms.

Aberrant FGFR Tyrosine Kinase Signaling Enhances the Warburg Effect by Reprogramming LDH Isoform Expression and Activity in Prostate Cancer

The acquisition of ectopic fibroblast growthfactor receptor 1 (FGFR1) expression is well documented in prostate cancer progression. How it contributes to prostate cancer progression is not fully understood, although it is known to confer a growth advantage and promote cell survival. Here, we report that FGFR1 tyrosine kinase reprograms the energy metabolism of prostate cancer cells by regulating the expression of lactate dehydrogenase (LDH) isozymes. FGFR1 increased LDHA stability through tyrosine phosphorylation and reduced LDHB expression by promoting its promoter methylation, thereby shifting cell metabolism from oxidative phosphorylation to aerobic glycolysis. LDHA depletion compromised, whereas LDHB depletion enhanced the tumorigenicity of prostate cancer cells. Furthermore, FGFR1 overexpression and aberrant LDH isozyme expression were associated with short overall survival and biochemical recurrence times in patients with prostate cancer. Our results indicate that ectopic FGFR1 expression reprograms the energy metabolism of prostate cancer cells, representing a hallmark change in prostate cancer progression.Significance: FGF signaling drives the Warburg effect through differential regulation of LDHA and LDHB, thereby promoting the progression of prostate cancer.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/16/4459/F1.large.jpg Cancer Res; 78(16); 4459-70. ©2018 AACR.

Protective Effect of Apigenin on Acrylonitrile-Induced Inflammation and Apoptosis in Testicular Cells via the NF-κB Pathway in Rats.

Apigenin (AP) as a plant flavonoid is found to attenuate acrylonitrile (ACN) toxicity by reducing ROS production and inhibiting apoptosis. Therefore, the present study aimed to evaluate the role of AP on ACN-induced inflammation and apoptosis in germ cells and whether it is through the NF-κB signaling pathway. AP increased the concentrations of lactate dehydrogenase isozyme (LDH) and sorbitol dehydrogenase (SDH), while the concentrations of interleukin β (IL-1β), tumor-necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were significantly reduced. AP could downregulate the expression of the nuclear factor of kappa B (NF-κB) and inhibit phosphorylation of the inhibitory κBα (IκBα). Cleaved caspase-3 was also upregulated by AP, and the apoptotic were less than those in the ACN group. These results suggest that AP might improve maturation and energy metabolism of testes, inhibit NF-κB activation. Then AP could further downregulate NF-κB signal and inhibit the germ cell apoptosis and reduce inflammatory caused by ACN.

Lactate Dehydrogenase Isozymes in the Tissues of Hibernating Bats (Chiroptera)

A comparative electrophoretic assay of lactate dehydrogenase (EC 1.1.1.27) isozymes has been carried out in the homogenates of the tissues of cardiac and skeletal muscles, liver, kidneys and lungs of five species of hibernating bats of the order Chiroptera: the northern bat Eptesicus nilssonii Keyserling and Blasius, the brown long-eared bat Plecotus auritus L., Brandt’s bat Myotis brandtii Eversmann, Daubenton’s bat Myotis daubentonii Kuhl, and the whiskered bat Myotis mystacinus Kuhl, which live in Karelia near the northern border of their distribution area. High contents of aerobic lactate dehydrogenase 1 and lactate dehydrogenase 2 isozymes have been detected in the skeletal muscle of the studied bats. The lactate dehydrogenase isozyme spectra of the tissues of kidneys and skeletal muscles from the smaller representatives of bats (the whiskered and Brandt’s bats) contained the highest content of H subunits among the studied species. In contrast, the predominance of M subunits has been revealed in the lactate dehydrogenase isozyme spectra of the kidneys of the northern and the brown long-eared bats. The discovered interspecies differences are discussed in the context of the adaptation of bats to hibernation.