Disturbance in the metabolism of 5′-methylthioadenosine and adenine in patients with neoplastic diseases, and in those with a deficiency in adenine phosphoribosyltransferase

Kaneko, Kiyoko; Fujimori, Shin; Kumakawa, Toshiro; Kamatani, Naoyuki; Akaoka, Ieo

doi:10.1016/0026-0495(91)90066-6

Cited by 4 publications

(3 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4D). MTAP-mediated MTA degradation is the main source of cellular adenine 25 . We also found that phosphoribosyl pyrophosphate (PRPP) was increased by 1.7- and 1.4-fold in HSP60-KD1 and -KD2 cells, respectively, while adenosine monophosphate (AMP), a product of the adenine phosphoribosyltransferase (APRT)-catalyzed reaction between adenine and PRPP 26 , was increased by 6.5- and 7-fold in HSP60-KD1 and -KD2 cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

HSP60-regulated Mitochondrial Proteostasis and Protein Translation Promote Tumor Growth of Ovarian Cancer

Guo

Zhang

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Ovarian cancer (OC) is the most lethal gynecological carcinoma due to the lack of diagnostic markers and effective drug targets. Discovery of new therapeutic targets in OC to improve the treatment outcome is urgently needed. We performed proteomic analysis of OC specimens and the paired normal tissues and revealed that proteins associated with mitochondrial proteostasis and protein translation were highly expressed in ovarian tumor tissues, indicating that mitochondria are required for tumor progression of OC. Heat shock protein 60 (HSP60), an important mitochondrial chaperone, was upregulated in ovarian tumors. HSP60 silencing significantly attenuated growth of OC cells in both cells and mice xenografts. Proteomic analysis revealed that HSP60 silencing downregulated proteins involved in mitochondrial functions and protein synthesis. Metabolomic analysis revealed that HSP60 silencing resulted in a more than 100-fold increase in cellular adenine levels, leading to increased adenosine monophosphate and an activated AMPK pathway, and consequently reduced mTORC1-mediated S6K and 4EBP1 phosphorylation to inhibit protein synthesis that suppressed the proliferation of OC cells. These results suggest that HSP60 knockdown breaks mitochondrial proteostasis, and inactivates the mTOR pathway to inhibit OC progression, suggesting that HSP60 is a potential therapeutic target for OC treatment.

show abstract

Section: Resultsmentioning

confidence: 99%

HSP60-regulated Mitochondrial Proteostasis and Protein Translation Promote Tumor Growth of Ovarian Cancer

Guo

Zhang

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Endogenously produced adenine is mainly derived from the cleavage of 5'-methylthioadenosine [11]. The conversion of 2'-dAdo to adenine represent a protective device to control the plasma level of 2'-dAdo when the activity of adenosine deaminase (ADA) is inhibited [12]. In the case of hepatocellular carcinoma, the level of adenine has been found to increase considerably [13].…”

Section: Introductionmentioning

confidence: 99%

Voltammetric Determination of 2′‐Deoxyadenosine and Adenine in Urine of Patients with Hepatocellular Carcinoma Using Fullerene‐C₆₀‐modified Glassy Carbon Electrode

2009

View full text Add to dashboard Cite

A fullerene-C 60 -modified glassy carbon electrode has been examined for the simultaneous determination of 2'-deoxyadenosine (2'-dAdo) and adenine in human blood and urine using Osteryoung square-wave voltammetry (OSWV) at pH 7.2. Compared to bare glassy carbon electrode (GCE), the modified electrode displays a shift of the oxidation potential in the negative direction with significant increase in the peak current for both the analytes. At modified electrode well-defined anodic peaks at potential of 1248 mV and 994 mV are observed for 2'-dAdo and adenine respectively. Linear calibration curves were obtained within the concentration range 10 nM to 100 mM for both the compounds in 0.1 M phosphate buffer solution (PBS) with the limit of detection 0.8 Â 10 À8 M and 0.95 Â 10 À8M for 2'-dAdo and adenine respectively. The analytical utility of the present method is demonstrated by quantitative detection of 2'-dAdo and adenine in human urine of normal subjects as well as in patients with hepatocellular carcinoma. Interfering effect of some coexisting metabolites has also been reported.

show abstract

“…2), is degraded to adenine by 5 0 -methylthioadenosine phosphorylase (MTAP). 27 Under normal conditions this pathway is the main source of endogenous adenine, which is efficiently salvaged to adenosine monophosphate (AMP) 28 (Fig. 2).…”

Section: Fsv Of 28-dha At N-cfs In Physiological Buffersmentioning

confidence: 99%

Rapid measurements of 2,8-dihydroxyadenine (2,8-DHA) with a nanostructured electrochemical sensor in 5-fold diluted supernatants of endothelial cells exposed to oxidative stress

Kathiwala

El-Nour

Cohen-Shohet

et al. 2010

Analyst

View full text Add to dashboard Cite

Fast scan cyclic voltammetry (FSV) with a nanostructured carbon fiber sensor (N-CFS) was developed for direct measurements of the purine metabolite 2,8-dihydroxyadenine (2,8-DHA; i.e. 6-amino-1H-purine-2,8-dione) in endothelial cell supernatants as a marker of cell stress. The 2,8-DHA was measured in the supernatant of aortic (AECs) and pulmonary artery endothelial cells (PAECs), which were maintained in Hank's Balanced Salt solution (HBSS) and exposed to physiological oxygen pressures as well as to oxidative stress, hypoxia (specifically 3% O(2) for AECs) and hyperoxia (20% O(2) for PAECs). Dilution of the supernatants with phosphate buffer in the ratio of 1 : 5 allowed the optimization of FSV measurements with the N-CFS in cell supernatants.The LOD for 2,8-DHA was 1 microM and the LDR was 2-15 microM with the sensitivity of (0.34 +/- 0.01) nA microM(-1) (R(2) = 0.99). The changes in 2,8-DHA concentration when the cells were exposed to stress confirm that PAECs can adapt to stress. However, the results also show that the tolerance of AECs to hypoxia is low. Cellular pathways involved in the response of PAECs and AECs to oxidative stress are outlined.

show abstract

Disturbance in the metabolism of 5′-methylthioadenosine and adenine in patients with neoplastic diseases, and in those with a deficiency in adenine phosphoribosyltransferase

Cited by 4 publications

References 21 publications

HSP60-regulated Mitochondrial Proteostasis and Protein Translation Promote Tumor Growth of Ovarian Cancer

HSP60-regulated Mitochondrial Proteostasis and Protein Translation Promote Tumor Growth of Ovarian Cancer

Voltammetric Determination of 2′‐Deoxyadenosine and Adenine in Urine of Patients with Hepatocellular Carcinoma Using Fullerene‐C₆₀‐modified Glassy Carbon Electrode

Rapid measurements of 2,8-dihydroxyadenine (2,8-DHA) with a nanostructured electrochemical sensor in 5-fold diluted supernatants of endothelial cells exposed to oxidative stress

Contact Info

Product

Resources

About

Disturbance in the metabolism of 5′-methylthioadenosine and adenine in patients with neoplastic diseases, and in those with a deficiency in adenine phosphoribosyltransferase

Cited by 4 publications

References 21 publications

HSP60-regulated Mitochondrial Proteostasis and Protein Translation Promote Tumor Growth of Ovarian Cancer

HSP60-regulated Mitochondrial Proteostasis and Protein Translation Promote Tumor Growth of Ovarian Cancer

Voltammetric Determination of 2′‐Deoxyadenosine and Adenine in Urine of Patients with Hepatocellular Carcinoma Using Fullerene‐C60‐modified Glassy Carbon Electrode

Rapid measurements of 2,8-dihydroxyadenine (2,8-DHA) with a nanostructured electrochemical sensor in 5-fold diluted supernatants of endothelial cells exposed to oxidative stress

Contact Info

Product

Resources

About

Voltammetric Determination of 2′‐Deoxyadenosine and Adenine in Urine of Patients with Hepatocellular Carcinoma Using Fullerene‐C₆₀‐modified Glassy Carbon Electrode