Downregulation by CNNM2 of ATP5MD Expression in the 10q24.32 Schizophrenia-Associated Locus Involved in Impaired ATP Production and Neurodevelopment

2020 ◽  
Author(s):  
Zhongju Wang ◽  
Yongchang Zhu ◽  
Linyan Ye ◽  
Qiyang Li ◽  
Bo Guo ◽  
...  
Keyword(s):  
Atp Production

The Oral Intake of Organic Germanium, Ge-132, Elevates α-Tocopherol Levels in the Plas-ma and Modulates Hepatic Gene Expression Profiles to Promote Immune Activation in Mice

2014 ◽  
Vol 84 (3-4) ◽  
pp. 0183-0195 ◽  
Author(s):  
Takashi Nakamura ◽  
Tomoya Takeda ◽  
Yoshihiko Tokuji
Keyword(s):  
Gene Expression ◽  
Immune Activation ◽  
Expression Profiles ◽  
Water Soluble ◽  
Alpha Tocopherol ◽  
Hepatic Gene Expression ◽  
Tocopherol Concentration ◽  
Altered Expression ◽  
Atp Production ◽  
Transfer Protein

The common water-soluble organic germanium compound poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) exhibits activities related to immune responses and antioxidant induction. In this study, we evaluated the antioxidative effect of dietary Ge-132 in the plasma of mice. Male ICR mice (seven mice per group) received an AIN-76 diet with 0.05 % Ge-132; three groups received the Ge-132-containing diet for 0, 1 or 4 days. The plasma alpha-tocopherol (α-tocopherol) concentration increased from 6.85 to 9.60 μg/ml after 4 days of Ge-132 intake (p < 0.05). We evaluated the changes in hepatic gene expression related to antioxidative activity as well as in the entire expression profile after one day of Ge-132 intake, using DNA microarray technology. We identified 1,220 genes with altered expression levels greater than 1.5-fold (increased or decreased) as a result of Ge-132 intake, and α-tocopherol transfer protein (Ttpa) gene expression was increased 1.62-fold. Immune activation was identified as the category with the most changes (containing 60 Gene Ontology (GO) term biological processes (BPs), 41 genes) via functional clustering analysis of altered gene expression. Ge-132 affected genes in clusters related to ATP production (22 GO term BPs, 21 genes), lipid metabolism (4 GO term BPs, 38 genes) and apoptosis (5 GO term BPs). Many GO term BPs containing these categories were significantly affected by the Ge-132 intake. Oral Ge-132 intake may therefore have increased plasma α-tocopherol levels by up-regulating α-tocopherol transfer protein (Ttpa) gene expression.

scholarly journals Cinnamon Oil Inhibits Penicillium expansum Growth by Disturbing the Carbohydrate Metabolic Process

2021 ◽  
Vol 7 (2) ◽  
pp. 123
Author(s):  
Tongfei Lai ◽  
Yangying Sun ◽  
Yaoyao Liu ◽  
Ran Li ◽  
Yuanzhi Chen ◽  
...  
Keyword(s):  
Pentose Phosphate ◽  
Metabolic Process ◽  
Penicillium Expansum ◽  
Economic Losses ◽  
Pome Fruit ◽  
Cinnamon Oil ◽  
Atp Production ◽  
Protein Levels ◽  
Regulatory Enzymes ◽  
Expression Of Genes

Penicillium expansum is a major postharvest pathogen that mainly threatens the global pome fruit industry and causes great economic losses annually. In the present study, the antifungal effects and potential mechanism of cinnamon oil against P. expansum were investigated. Results indicated that 0.25 mg L−1 cinnamon oil could efficiently inhibit the spore germination, conidial production, mycelial accumulation, and expansion of P. expansum. In addition, it could effectively control blue mold rots induced by P. expansum in apples. Cinnamon oil could also reduce the expression of genes involved in patulin biosynthesis. Through a proteomic quantitative analysis, a total of 146 differentially expressed proteins (DEPs) involved in the carbohydrate metabolic process, most of which were down-regulated, were noticed for their large number and functional significance. Meanwhile, the expressions of 14 candidate genes corresponding to DEPs and the activities of six key regulatory enzymes (involving in cellulose hydrolyzation, Krebs circle, glycolysis, and pentose phosphate pathway) showed a similar trend in protein levels. In addition, extracellular carbohydrate consumption, intracellular carbohydrate accumulation, and ATP production of P. expansum under cinnamon oil stress were significantly decreased. Basing on the correlated and mutually authenticated results, we speculated that disturbing the fungal carbohydrate metabolic process would be partly responsible for the inhibitory effects of cinnamon oil on P. expansum growth. The findings would provide new insights into the antimicrobial mode of cinnamon oil.

scholarly journals Investigation of energy metabolic dynamism in hyperthermia-resistant ovarian and uterine cancer cells under heat stress

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Taisei Kanamori ◽  
Natumi Miyazaki ◽  
Shigeki Aoki ◽  
Kousei Ito ◽  
Akihiro Hisaka ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Uterine Cancer ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Ubiquitin Pathway ◽  
Atp Production ◽  
Skov3 Cells ◽  
Pathway Analyses ◽  
Rate Limiting ◽  
Glycolytic Rate ◽  
The Warburg Effect

AbstractDespite progress in the use of hyperthermia in clinical practice, the thermosensitivity of cancer cells is poorly understood. In a previous study, we found that sensitivity to hyperthermia varied between ovarian and uterine cancer cell lines. Upon hyperthermia, glycolytic enzymes decreased in hyperthermia-resistant SKOV3 cells. However, the mechanisms of glycolysis inhibition and their relationship with thermoresistance remain to be explored. In this study, metabolomic analysis indicated the downregulation of glycolytic metabolites in SKOV3 cells after hyperthermia. Proteomic and pathway analyses predicted that the ubiquitin pathway was explicitly activated in resistant SKOV3 cells, compared with hyperthermia-sensitive A2780 cells, and STUB1, a ubiquitin ligase, potentially targeted PKM, a glycolytic rate-limiting enzyme. PKM is degraded via ubiquitination upon hyperthermia. Although glycolysis is inactivated by hyperthermia, ATP production is maintained. We observed that oxygen consumption and mitochondrial membrane potential were activated in SKOV3 cells but suppressed in A2780 cells. The activation of mitochondria could compensate for the loss of ATP production due to the suppression of glycolysis by hyperthermia. Although the physiological significance has not yet been elucidated, our results demonstrated that metabolomic adaptation from the Warburg effect to mitochondrial oxidative phosphorylation could contribute to thermoresistance in ovarian and uterine cancer cells.

scholarly journals Long-Term Cryopreservation Does Not Affect Quality of Peripheral Blood Stem Cell Grafts: A Comparative Study of Native, Short-Term and Long-Term Cryopreserved Haematopoietic Stem Cells

2021 ◽  
Vol 30 ◽  
pp. 096368972110360
Author(s):  
Daniel Lysak ◽  
Michaela Brychtová ◽  
Martin Leba ◽  
Miroslava Čedíková ◽  
Daniel Georgiev ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Statistical Significance ◽  
Extended Period ◽  
High Dose ◽  
Atp Production ◽  
Cd34 Cells ◽  
Negative Effect

Cryopreserved haematopoietic progenitor cells are used to restore autologous haematopoiesis after high dose chemotherapy. Although the cells are routinely stored for a long period, concerns remain about the maximum storage time and the possible negative effect of storage on their potency. We evaluated the effect of cryopreservation on the quality of peripheral stem cell grafts stored for a short (3 months) and a long (10 years) period and we compared it to native products.The viability of CD34+ cells remained unaffected during storage, the apoptotic cells were represented up to 10% and did not differ between groups. The clonogenic activity measured by ATP production has decreased with the length of storage (ATP/cell 1.28 nM in native vs. 0.63 in long term stored products, P < 0.05). Only borderline changes without statistical significance were detected when examining mitochondrial and aldehyde dehydrogenase metabolic activity and intracellular pH, showing their good preservation during cell storage. Our experience demonstrates that cryostorage has no major negative effect on stem cell quality and potency, and therefore autologous stem cells can be stored safely for an extended period of at least 10 years. On the other hand, long term storage for 10 years and longer may lead to mild reduction of clonogenic capacity. When a sufficient dose of stem cells is infused, these changes will not have a clinical impact. However, in products stored beyond 10 years, especially when a low number of CD34+ cells is available, the quality of stem cell graft should be verified before infusion using the appropriate potency assays.

scholarly journals DDR1 Affects Metabolic Reprogramming in Breast Cancer Cells by Cross-Talking to the Insulin/IGF System

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 926
Author(s):  
Veronica Vella ◽  
Marika Giuliano ◽  
Maria Luisa Nicolosi ◽  
Maria Giovanna Majorana ◽  
Małgorzata Anna Marć ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Cells ◽  
Cell Metabolism ◽  
Growth Factor Receptor ◽  
Metabolic Reprogramming ◽  
Atp Production ◽  
Igf System ◽  
Putative Target ◽  
Collagen Receptor ◽  
Discoidin Domain Receptor 1

The insulin receptor isoform A (IR-A), a dual receptor for insulin and IGF2, plays a role in breast cancer (BC) progression and metabolic reprogramming. Notably, discoidin domain receptor 1 (DDR1), a collagen receptor often dysregulated in cancer, is involved in a functional crosstalk and feed forward loop with both the IR-A and the insulin like growth factor receptor 1 (IGF1R). Here, we aimed at investigating whether DDR1 might affect BC cell metabolism by modulating the IGF1R and/or the IR. To this aim, we generated MCF7 BC cells engineered to stably overexpress either IGF2 (MCF7/IGF2) or the IR-A (MCF7/IR-A). In both cell models, we observed that DDR1 silencing induced a significant decrease of total ATP production, particularly affecting the rate of mitochondrial ATP production. We also observed the downregulation of key molecules implicated in both glycolysis and oxidative phosphorylation. These metabolic changes were not modulated by DDR1 binding to collagen and occurred in part in the absence of IR/IGF1R phosphorylation. DDR1 silencing was ineffective in MCF7 knocked out for DDR1. Taken together, these results indicate that DDR1, acting in part independently of IR / IGF1R stimulation, might work as a novel regulator of BC metabolism and should be considered as putative target for therapy in BC.

scholarly journals HO-1 Modulates Aerobic Glycolysis through LDH in Prostate Cancer Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 966
Author(s):  
Florencia Cascardo ◽  
Nicolás Anselmino ◽  
Alejandra Páez ◽  
Estefanía Labanca ◽  
Pablo Sanchis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Aerobic Glycolysis ◽  
Heme Oxygenase 1 ◽  
Free Survival ◽  
Atp Production ◽  
Inflammatory Damage ◽  
Extracellular Lactate ◽  
Cellular Energetics ◽  
Lactate Levels

Prostate cancer (PCa) is the second most diagnosed malignancy and the fifth leading cause of cancer associated death in men worldwide. Dysregulation of cellular energetics has become a hallmark of cancer, evidenced by numerous connections between signaling pathways that include oncoproteins and key metabolic enzymes. We previously showed that heme oxygenase 1 (HO-1), a cellular homeostatic regulator counteracting oxidative and inflammatory damage, exhibits anti-tumoral activity in PCa cells, inhibiting cell proliferation, migration, tumor growth and angiogenesis. The aim of this study was to assess the role of HO-1 on the metabolic signature of PCa. After HO-1 pharmacological induction with hemin, PC3 and C4-2B cells exhibited a significantly impaired cellular metabolic rate, reflected by glucose uptake, ATP production, lactate dehydrogenase (LDH) activity and extracellular lactate levels. Further, we undertook a bioinformatics approach to assess the clinical significance of LDHA, LDHB and HMOX1 in PCa, identifying that high LDHA or low LDHB expression was associated with reduced relapse free survival (RFS). Interestingly, the shortest RFS was observed for PCa patients with low HMOX1 and high LDHA, while an improved prognosis was observed for those with high HMOX1 and LDHB. Thus, HO-1 induction causes a shift in the cellular metabolic profile of PCa, leading to a less aggressive phenotype of the disease.

scholarly journals Bioenergetic and metabolic impairments in Duchenne Muscular Dystrophy (DMD) patients' iPSC-derived cardiomyocytes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Willi ◽  
B Agranovich ◽  
I Abramovich ◽  
D Freimark ◽  
M Arad ◽  
...  
Keyword(s):  
Stress Test ◽  
Young Male ◽  
Induced Pluripotent Stem Cell ◽  
Dystrophin Gene ◽  
Energy System ◽  
Basal Respiration ◽  
Mitochondrial Activity ◽  
Funding Source ◽  
Atp Production ◽  
Metabolic Impairments

Abstract Introduction DMD, an X-linked muscle degenerative fatal disease, is caused by mutations in the dystrophin gene. Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality in DMD patients. Treatments for DCM in DMD are limited to steroids and standard heart failure medications such as β-blockers and ACE-inhibitors, and therefore novel therapeutic modalities are urgently needed. Purpose We hypothesized that dystrophin mutations in DMD lead to cardiomyopathy-causing bioenergetic/metabolic impairments, which can be therapeutically targeted for improving cardiac function. Methods Induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CMs) were generated from healthy volunteer and 3 DMD patients: young male (YM), adult male (AM) and adult female (AF). We investigated the bioenergetics, electrophysiology, mitochondrial and metabolic features of healthy and DMD iPSC-CMs using the Seahorse Flux analyzer, patch clamp, confocal fluorescence microscopy and Liquid chromatography mass spectrometry (LC-MS) technologies, respectively. Results To test the hypothesis, we measured respiration and glycolytic rates of healthy and DMD iPSC-CMs. Compared to healthy iPSC-CMs, in both AM and AF DMD, but not in YM DMD cardiomyocytes, there was a 75% decrease in ATP production, and 80% and 45% decrease in basal respiration, respectively. In agreement with the healthy-like bioenergetic status of YM, the iPSC-CMs showed no arrhythmias, in contrast to the prominent arrhythmias in AM and AF cardiomyocytes. To determine whether the impairment in the phosphorylation pathway (OXPHOS) affects glycolysis, we measured the cardiomyocytes' response to glycolytic stress test. These experiments showed that the glycolytic rates were similar in healthy and DMD iPSC-CMs. In agreement with impaired OXPHOS, mitochondrial activity measured by 3D life confocal microscopy was attenuated in the DMD male by 35%, compared to healthy cardiomyocytes. Furthermore, the metabolomic LC-MS analyses demonstrated significant differences in metabolite levels in YM, AM and AF DMD iPSC-CMs relative to healthy iPSC-CMs. For example, compared to healthy iPSC-CMs, there was a dramatic fall to undetected levels in phosphocreatine in both AM and AF, but not in YM DMD, indicating a dysfunctional phosphocreatine energy system. Conclusions DMD iPSC-CMs exhibit bioenergetic/metabolic impairments, which constitute novel targets for alleviating the cardiomyopathy in DMD patients. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): ISF - Israel Science Foundation

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