scholarly journals The short isoform of PRLR suppresses the pentose phosphate pathway and nucleotide synthesis through the NEK9-Hippo axis in pancreatic cancer

Theranostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 3898-3915
Author(s):  
Huizhen Nie ◽  
Pei-Qi Huang ◽  
Shu-Heng Jiang ◽  
Qin Yang ◽  
Li-Peng Hu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pentose Phosphate Pathway ◽  
Pentose Phosphate ◽  
Nucleotide Synthesis

scholarly journals Annurca Apple Polyphenols Ignite Keratin Production in Hair Follicles by Inhibiting the Pentose Phosphate Pathway and Amino Acid Oxidation

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1406 ◽  
Author(s):  
Nadia Badolati ◽  
Eduardo Sommella ◽  
Gennaro Riccio ◽  
Emanuela Salviati ◽  
Dimitri Heintz ◽  
...  
Keyword(s):  
Pentose Phosphate Pathway ◽  
Hair Growth ◽  
High Resolution Mass Spectrometry ◽  
Negative Impact ◽  
Adult Population ◽  
Pentose Phosphate ◽  
Hair Follicles ◽  
Acid Oxidation ◽  
Healthy Human ◽  
Nucleotide Synthesis

Patterned hair loss (PHL) affects around 50% of the adult population worldwide. The negative impact that this condition exerts on people’s life quality has boosted the appearance of over-the-counter products endowed with hair-promoting activity. Nutraceuticals enriched in polyphenols have been recently shown to promote hair growth and counteract PHL. Malus pumila Miller cv. Annurca is an apple native to Southern Italy presenting one of the highest contents of Procyanidin B2. We have recently shown that oral consumption of Annurca polyphenolic extracts (AAE) stimulates hair growth, hair number, hair weight and keratin content in healthy human subjects. Despite its activity, the analysis of the molecular mechanism behind its hair promoting effect is still partially unclear. In this work we performed an unprecedented metabolite analysis of hair follicles (HFs) in mice topically treated with AAE. The metabolomic profile, based on a high-resolution mass spectrometry approach, revealed that AAE re-programs murine HF metabolism. AAE acts by inhibiting several NADPH dependent reactions. Glutaminolysis, pentose phosphate pathway, glutathione, citrulline and nucleotide synthesis are all halted in vivo by the treatment of HFs with AAE. On the contrary, mitochondrial respiration, β-oxidation and keratin production are stimulated by the treatment with AAE. The metabolic shift induced by AAE spares amino acids from being oxidized, ultimately keeping them available for keratin biosynthesis.

scholarly journals p53 coordinates DNA repair with nucleotide synthesis by suppressing PFKFB3 expression and promoting the pentose phosphate pathway

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Derek A. Franklin ◽  
Yizhou He ◽  
Patrick L. Leslie ◽  
Andrey P. Tikunov ◽  
Nick Fenger ◽  
...  
Keyword(s):  
Dna Repair ◽  
Pentose Phosphate Pathway ◽  
Pentose Phosphate ◽  
Nucleotide Synthesis

scholarly journals The Pentose Phosphate Pathway in Cancer: Regulation and Therapeutic Opportunities

Chemotherapy ◽  
2021 ◽  
pp. 1-13
Author(s):  
Noorhan Ghanem ◽  
Chirine El-Baba ◽  
Khaled Araji ◽  
Riyad El-Khoury ◽  
Julnar Usta ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Pentose Phosphate Pathway ◽  
Aerobic Glycolysis ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Pentose Phosphate ◽  
Nucleotide Synthesis ◽  
Intermediary Metabolites ◽  
Dividing Cells ◽  
Metabolites Production ◽  
Reductive Metabolism

<b><i>Background:</i></b> Tumorigenesis is associated with deregulation of nutritional requirements, intermediary metabolites production, and microenvironment interactions. Unlike their normal cell counterparts, tumor cells rely on aerobic glycolysis, through the Warburg effect. <b><i>Summary:</i></b> The pentose phosphate pathway (PPP) is a major glucose metabolic shunt that is upregulated in cancer cells. The PPP comprises an oxidative and a nonoxidative phase and is essential for nucleotide synthesis of rapidly dividing cells. The PPP also generates nicotinamide adenine dinucleotide phosphate, which is required for reductive metabolism and to counteract oxidative stress in tumor cells. This article reviews the regulation of the PPP and discusses inhibitors that target its main pathways. <b><i>Key Message:</i></b> Exploiting the metabolic vulnerability of the PPP offers potential novel therapeutic opportunities and improves patients’ response to cancer therapy.

scholarly journals Silencing Sirtuin5 induces DNA damage by suppressing the pentose phosphate pathway in a demalonylation-dependent manner: A possible target for anticancer therapy in CRC

2021 ◽  
Author(s):  
Hao-Lian Wang ◽  
Yan Chen ◽  
Yun-Qian Wang ◽  
En-Wei Tao ◽  
Juan Tan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Pentose Phosphate Pathway ◽  
Pentose Phosphate ◽  
Dependent Manner ◽  
Class Iii ◽  
Nucleotide Synthesis ◽  
Cycle Arrest

Abstract A previous study by our research group showed that sirtuin5 (SIRT5), a member of the class III NAD＋-dependent deacetylase family, is highly expressed in colorectal cancer (CRC). The present study showed that deletion of SIRT5 induced cell cycle arrest and apoptosis as a result of continuous and irreparable DNA damage in CRC cells, a consequence of the impaired production of ribose-5-phosphate (R5P) which is essential for nucleotide synthesis. Consistently, the cell cycle arrest and apoptosis induced by SIRT5 silencing could be reversed by supplementation with four nucleotides. Moreover, metabolic profiling revealed that silencing of SIRT5 could inhibit the non-oxidative pentose phosphate pathway (PPP), which produces R5P, required for base ribosylation. Notably, SIRT5 activates transketolase (TKT), the key enzyme in the cellular non-oxidative PPP, by mediating its lysine demalonylation through the interaction between SIRT5 and TKT. Furthermore, the results demonstrated that TKT is essential for the SIRT5-induced malignant phenotypes of CRC, both in vivo and in vitro. These results therefore revealed that the increased lysine malonylation levels of TKT caused by silencing SIRT5 suppresses non-oxidative pentose phosphate metabolism, leading to a low-nucleotide pool. This in turn induces DNA damage in tumor cells and inhibits proliferation, suggesting that SIRT5 may serve as a potential anticancer target.

scholarly journals Systematic Identification of Regulators of Oxidative Stress Reveals Non-canonical Roles for Peroxisomal Import and the Pentose Phosphate Pathway

Cell Reports ◽  
2020 ◽  
Vol 30 (5) ◽  
pp. 1417-1433.e7 ◽  
Author(s):  
Michael M. Dubreuil ◽  
David W. Morgens ◽  
Kanji Okumoto ◽  
Masanori Honsho ◽  
Kévin Contrepois ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pentose Phosphate Pathway ◽  
Pentose Phosphate ◽  
Systematic Identification

scholarly journals Geranylgeranylacetone attenuates cerebral ischemia–reperfusion injury in rats through the augmentation of HSP 27 phosphorylation: a preliminary study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kazuya Matsuo ◽  
Kohkichi Hosoda ◽  
Jun Tanaka ◽  
Yusuke Yamamoto ◽  
Taichiro Imahori ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Pentose Phosphate Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Pentose Phosphate ◽  
Cerebral Ischemia Reperfusion ◽  
Hsp27 Phosphorylation ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Preliminary Study

Abstract Background We previously reported that heat shock protein 27 (HSP27) phosphorylation plays an important role in the activation of glucose-6-phosphate dehydrogenase (G6PD), resulting in the upregulation of the pentose phosphate pathway and antioxidant effects against cerebral ischemia–reperfusion injury. The present study investigated the effect of geranylgeranylacetone, an inducer of HSP27, on ischemia–reperfusion injury in male rats as a preliminary study to see if further research of the effects of geranylgeranylacetone on the ischemic stroke was warranted. Methods In all experiments, male Wistar rats were used. First, we conducted pathway activity profiling based on a gas chromatography–mass spectrometry to identify ischemia–reperfusion-related metabolic pathways. Next, we investigated the effects of geranylgeranylacetone on the pentose phosphate pathway and ischemia–reperfusion injury by real-time polymerase chain reaction (RT-PCR), immunoblotting, and G6PD activity, protein carbonylation and infarct volume analysis. Geranylgeranylacetone or vehicle was injected intracerebroventricularly 3 h prior to middle cerebral artery occlusion or sham operation. Results Pathway activity profiling demonstrated that changes in the metabolic state depended on reperfusion time and that the pentose phosphate pathway and taurine-hypotaurine metabolism pathway were the most strongly related to reperfusion among 137 metabolic pathways. RT-PCR demonstrated that geranylgeranylacetone did not significantly affect the increase in HSP27 transcript levels after ischemia–reperfusion. Immunoblotting showed that geranylgeranylacetone did not significantly affect the elevation of HSP27 protein levels. However, geranylgeranylacetone significantly increase the elevation of phosphorylation of HSP27 after ischemia–reperfusion. In addition, geranylgeranylacetone significantly affected the increase in G6PD activity, and reduced the increase in protein carbonylation after ischemia–reperfusion. Accordingly, geranylgeranylacetone significantly reduced the infarct size (median 31.3% vs 19.9%, p = 0.0013). Conclusions As a preliminary study, these findings suggest that geranylgeranylacetone may be a promising agent for the treatment of ischemic stroke and would be worthy of further study. Further studies are required to clearly delineate the mechanism of geranylgeranylacetone-induced HSP27 phosphorylation in antioxidant effects, which may guide the development of new approaches for minimizing the impact of cerebral ischemia–reperfusion injury.

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