On the Stability of Key Enzymes of Energy Metabolism in Muscle Biopsies

Enzyme ◽  
1990 ◽  
Vol 43 (4) ◽  
pp. 183-187 ◽  
Author(s):  
Th. Pache ◽  
H. Reichmann
2008 ◽  
Vol 26 (3-4) ◽  
pp. 293-299 ◽  
Author(s):  
Carolina Maso Viegas ◽  
Gustavo Costa Ferreira ◽  
Patrícia Fernanda Schuck ◽  
Anelise Miotti Tonin ◽  
Ângela Zanatta ◽  
...  

1995 ◽  
Vol 6 (1) ◽  
pp. 68-74
Author(s):  
A Conjard ◽  
B Ferrier ◽  
M Martin ◽  
A Caillette ◽  
H Carrier ◽  
...  

In order to improve knowledge about the mechanisms underlying the alterations of energy metabolism recently observed in the skeletal muscle of patients suffering from chronic renal failure, this study was designed to test (1) whether changes in the activity of key enzymes of energy metabolism occur in the muscle of these patients, and if so (2) whether the different muscle fiber types are equally altered in their metabolic machinery. For this, the maximum activities of 14 enzymes were measured in individual muscle fibers microdissected from biopsies of rectus abdominis muscle obtained from seven normal subjects and seven patients with end-stage renal failure before renal replacement therapy. A large decrease in the activities of beta-hydroxyacyl-coenzyme A dehydrogenase, a key enzyme of the beta-oxidation pathway, of citrate synthase, which initiates the tricarboxylic acid cycle, and of fructose-1,6-bisphosphatase, which contributes to the synthesis of glycogen from lactate, was observed in the three fiber types (slow-twitch oxidative, fast-twitch oxidative-glycolytic, and fast-twitch glycolytic). A smaller reduction of the activities of phosphofructokinase and/or pyruvate kinase, two key enzymes of glycolysis, was also observed in slow-twitch oxidative and/or fast-twitch oxidative-glycolytic fibers. These results demonstrate that the abnormalities of muscle energy metabolism observed in patients with chronic renal failure are due, at least in part, to intrinsic changes in the key enzymes of major energy-providing pathways; they also offer a satisfactory explanation for the defect of oxidative metabolism recently demonstrated in the muscle of these patients.


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A778-A778
Author(s):  
Minhyuk Yun ◽  
Goo-Young Kim ◽  
Sang Woo Jo ◽  
Changhoon In ◽  
Gyu-Young Moon ◽  
...  

BackgroundNAD(P)H-quinone oxidoreductase 1 (NQO1) is a cytosolic two-electron oxidoreductase overexpressed in many types of cancers, including breast cancer, pancreatic cancer, colorectal cancer, cholangiocarcinoma, uterine cervical cancer, melanoma, and lung cancer.1Up-regulation of NQO1 protects cells from oxidative stress and various cytotoxic quinones and is associated with late clinical stage, poor prognosis and lymph node metastasis.2 3 NQO1 increases stability of HIF-1α protein, which has been implicated in survival, proliferation, and malignance of cancer.1 Therefore, accumulating evidences suggest NQO1 as a promising therapeutic target for cancer. Accordingly, we have characterized the effect of a novel synthetic NQO1 substrate SBSC-S3001, and demonstrated its selective cytotoxic effects in cancer cells with high expression of NQO1.MethodsIn vitro cytotoxicity was determined by sulforhodamine B (SRB) assay in cancer cells with high NQO1 expression and CRISPR-mediated NQO1 knockout cells. The effect of SBSC-S3001 on the energy metabolism pathway was evaluated by western blot analysis of metabolism associated proteins from NQO1-overexpressed cancer cells treated with the compound for 24 hours. In vivo anti-tumor activity was evaluated in MC38 syngeneic and DLD-1 orthotopic mice models.ResultsSBSC-S3001 exhibited selective cytotoxicity in cancer cells with high expression of NQO1 in a dose-dependent manner. The cytotoxicity was observed in both normoxia and hypoxia conditions, correlating with the energy metabolism, mitochondrial biogenesis, and cancer proliferative pathways. Also, stronger cytotoxicity was observed in NQO1-overexpressed cancer cells treated with SBSC-S3001 compared to beta-lapachone and analogue treatment.4 When evaluated in vivo, SBSC-S3001 effectively inhibited the growth of syngeneic and orthotopic tumors when administered as a monotherapy. SBSC-S3001 treatment associated with reduction in key enzymes of the glycolytic pathway (LDHa and GAPDH) and HIF-1α and increase in levels of mitochondrial oxidative phosphorylation (OXPHOS) complex.ConclusionsTreatment of SBSC-S3001, a novel, NQO1-specific substrate reduces HIF-1α and key enzymes associated with glycolysis and suppresses the growth of tumors overexpressing NQO1. Further characterization of SBSC-S3001 as a novel metabolic anti-cancer agent for cancers with NQO1 overexpression is warranted.Ethics ApprovalThe study was approved by Samyang Biopharmaceuticals Institution’s Ethics Board, approval number SYAU2031.ReferencesOh ET, Kim JW, Kim JMet. al., NQO1 inhibits proteasome-mediated degradation of HIF-1α. Nat Commun 2016; 14:13593.Ma, Y. et al. NQO1 overexpression is associated with poor prognosis in squamous cell carcinoma of the uterine cervix. BMC Cancer 2014;14: 414Yang, Y. et al. Clinical implications of high NQO1 expression in breast cancers. J. Exp. Clin. Cancer Res 2014;33:144.Yang Y, Zhou X, Xu M, et al., β-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in NQO1-positive breast cancers. Sci Rep 2017;7:2681.


Metabolism ◽  
1987 ◽  
Vol 36 (8) ◽  
pp. 761-767 ◽  
Author(s):  
Maggie M.-Y. Chi ◽  
Carol S. Hintz ◽  
Deidre McKee ◽  
Steven Felder ◽  
Natasha Grant ◽  
...  

1992 ◽  
Vol 49 (1) ◽  
pp. 110-115 ◽  
Author(s):  
S. Hinterleitner ◽  
M. Huber ◽  
R. Lackner ◽  
W. Wieser

Juveniles of the zooplanktivorous Danube bleak (Chalcalburnus chalcoides mento) and of the benthivorous nase (Chondrostoma nasus) were subjected to an endurance training regime for 81–90 d. Growth performance was better in trained than in untrained Danube bleak but not in nase. Mass specific heart size was significantly greater in trained than in untrained C. nasus, but no difference was found in C. chalcoides. The size of muscle fibres increased with training in both species; in nase the red and pink fibres and in Danube bleak the red and white fibres exhibited the most conspicuous response. Mass specific activities of the enzymes of energy metabolism were generally not affected by training, but in the white fibres of C. chalcoides, three glycolytic enzymes displayed a parallel trend indicating an increase of the glycolytic potential with training of about 25%. Since the Danube bleak maintains an irregular, burst-like mode of swimming even under the endurance training regime, we assume the lactate produced intermittently in the white muscles to be oxidized in the heart and the red muscles. The activities of three glycolytic heart enzymes were up to 25-fold higher in C. chalcoides than in C. nasus.


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