Creatine in Cell Metabolism and Its Protective Action in Cerebral Ischemia

Колпакова, М. Э.; Веселкина, О. С.; Власов, Т. Д.

doi:10.1007/s11055-015-0098-4

Cited by 4 publications

(4 citation statements)

References 62 publications

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“…Decreased creatine has already been reported as a marker for highly proliferative cells and is found in gliomas. 27 This is in contrast to its antioxidant and antiproliferative effects when elevated 28 , as also demonstrated in our work where bevacizumab treatment on mIDH1-U87 cells produced elevated creatine in the area 2.95 ppm and 3.02 ppm with increases of 15% and 25%, respectively.…”

Section: Discussionsupporting

confidence: 72%

Nuclear magnetic resonance metabolic fingerprint of bevacizumab in mutant IDH1 glioma cells

Mesti

Bouchemal

Banissi

et al. 2018

Radiology and Oncology

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BackgroundMalignant gliomas are rapidly growing tumours that extensively invade the brain and have bad prognosis. Our study was performed to assess the metabolic effects of bevacizumab on the glioma cells carrying the IDH1 mutation, a mutation, associated with better prognosis and treatment outcome. Bevacizumab is known to inhibit tumour growth by neutralizing the biological activity of vascular endothelial growth factor (VEGF). However, the direct effects of bevacizumab on tumour cells metabolism remain poorly known.Materials and methodsThe immunoassay and MTT assay were used to assess the concentration of secreted VEGF and cell viability after bevacizumab exposure. Metabolomic studies on cells were performed using high resolution magic angle spinning spectroscopy (HRMAS).ResultsmIDH1-U87 cells secreted VEGF (13 ng/mL). Regardless, bevacizumab had no cytotoxic effect, even after a 72h exposure and with doses as high as 1 mg/mL. Yet, HRMAS analysis showed a significant effect of bevacizumab (0.1 mg/mL) on the metabolic phenotype of mIDH1-U87 cells with elevation of 2-hydroxyglutarate and changes in glutamine group metabolites (alanine, glutamate, glycine) and lipids (polyunsaturated fatty acids [PUFA], glycerophosphocholine, and phosphocholine).ConclusionsIn mIDH1-U87 cells, changes in glutamine group metabolites and lipids were identified as metabolic markers of bevacizumab treatment. These data support the possibility of a functional tricarboxylic acid cycle that runs in reductive manner, as a probable mechanism of action of bevacizumab in IDH1 mutated gliomas and propose a new target pathway for effective treatment of malignant gliomas.

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Section: Discussionsupporting

confidence: 72%

Nuclear magnetic resonance metabolic fingerprint of bevacizumab in mutant IDH1 glioma cells

Mesti

Bouchemal

Banissi

et al. 2018

Radiology and Oncology

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“…Creatine is present in both neurons and glial cells, and glial cells are known to be more resistant to ischemia. 39 This issue might explain the observation of delayed reduction in creatine concentrations within the infarction in our work and in previous studies. 33,34 Choline is a marker of cellular membrane turnover, through its involvement in membrane synthesis and degradation.…”

Section: Discussionsupporting

confidence: 66%

“…The greater and more rapid reduction in NAA level in infarction may indicate a higher susceptibility to ischemia for neurons. Creatine is present in both neurons and glial cells, and glial cells are known to be more resistant to ischemia 39 . This issue might explain the observation of delayed reduction in creatine concentrations within the infarction in our work and in previous studies 33,34 …”

Section: Discussionsupporting

confidence: 55%

Predicting the Onset of Ischemic Stroke With Fast High‐Resolution 3D MR Spectroscopic Imaging

Lin

Meng

Wang

et al. 2023

Magnetic Resonance Imaging

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Background Neurometabolite concentrations provide a direct index of infarction progression in stroke. However, their relationship with stroke onset time remains unclear. Purpose To assess the temporal dynamics of N‐acetylaspartate (NAA), creatine, choline, and lactate and estimate their value in predicting early (<6 hours) vs. late (6–24 hours) hyperacute stroke groups. Study Type Cross‐sectional cohort. Population A total of 73 ischemic stroke patients scanned at 1.8–302.5 hours after symptom onset, including 25 patients with follow‐up scans. Field Strength/Sequence A 3 T/magnetization‐prepared rapid acquisition gradient echo sequence for anatomical imaging, diffusion‐weighted imaging and fluid‐attenuated inversion recovery imaging for lesion delineation, and 3D MR spectroscopic imaging (MRSI) for neurometabolic mapping. Assessment Patients were divided into hyperacute (0–24 hours), acute (24 hours to 1 week), and subacute (1–2 weeks) groups, and into early (<6 hours) and late (6–24 hours) hyperacute groups. Bayesian logistic regression was used to compare classification performance between early and late hyperacute groups by using different combinations of neurometabolites as inputs. Statistical Tests Linear mixed effects modeling was applied for group‐wise comparisons between NAA, creatine, choline, and lactate. Pearson's correlation analysis was used for neurometabolites vs. time. P < 0.05 was considered statistically significant. Results Lesional NAA and creatine were significantly lower in subacute than in acute stroke. The main effects of time were shown on NAA (F = 14.321) and creatine (F = 12.261). NAA was significantly lower in late than early hyperacute patients, and was inversely related to time from symptom onset across both groups (r = −0.440). The decrease of NAA and increase of lactate were correlated with lesion volume (NAA: r = −0.472; lactate: r = 0.366) in hyperacute stroke. Discrimination was improved by combining NAA, creatine, and choline signals (area under the curve [AUC] = 0.90). Data Conclusion High‐resolution 3D MRSI effectively assessed the neurometabolite changes and discriminated early and late hyperacute stroke lesions. Evidence Level 1. Technical Efficacy Stage 2.

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“…The high serum aspartate content and high ovarian expression of arginase2 and odc1 at stage II and III indicated the active synthesis of polyamines, including putrescine and spermidine via the arginine metabolism pathway, for the control of cell proliferation and differentiation during earlier ovarian development [35]. Besides, as the cell energy shuttle (phosphocreatine can regenerate ATP), creatine plays a critical role in regulating energy metabolism [36]. The high serum contents of creatine related metabolites and the high ovarian mRNA expressions of gatm (encoding glycine amidinotransferase) and crt1 (encoding creatine transport protein) at stage II and III indicate the active creatine supply to the ovary, which might be a metabolic response to the high energy demand of developing ovaries.…”

Section: Plos Onementioning

confidence: 99%

Metabolomics and gene expressions revealed the metabolic changes of lipid and amino acids and the related energetic mechanism in response to ovary development of Chinese sturgeon (Acipenser sinensis)

Zhu

Leng

et al. 2020

PLoS ONE

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Captive breeding has been explored in Chinese sturgeon (Acipenser sinensis) for species protection. However, gonad development from stage II to IV of cultured female broodstocks is a handicap. This study aimed to explore the physiological and metabolic changes during the ovary development from stage II to IV of female Chinese sturgeon and the related energy regulatory mechanism, which may be helpful to address the developmental obstacle. The results showed that the oocyte volume increased and the muscle lipid content decreased with the ovary development. Ovarian RNA levels of most genes related to lipid and amino acid metabolism were higher in stage II and III than in stage IV. Serum contents of differential metabolites in arginine, cysteine, methionine, purine, tyrosine, lysine, valine, leucine and isoleucine metabolism pathways peaked at stage III, while the contents of sarcosine, alanine and histidine, as well as most oxylipins derived from fatty acids peaked at stage IV. These results indicated the more active amino acids, lipid metabolism, and energy dynamics of fish body in response to the high energy input of ovary developing from stage II to III, and the importance of alanine, histidine, taurine, folate and oxylipins for fish with ovary at stage IV.

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Creatine in Cell Metabolism and Its Protective Action in Cerebral Ischemia

Cited by 4 publications

References 62 publications

Nuclear magnetic resonance metabolic fingerprint of bevacizumab in mutant IDH1 glioma cells

Nuclear magnetic resonance metabolic fingerprint of bevacizumab in mutant IDH1 glioma cells

Predicting the Onset of Ischemic Stroke With Fast High‐Resolution 3D MR Spectroscopic Imaging

Metabolomics and gene expressions revealed the metabolic changes of lipid and amino acids and the related energetic mechanism in response to ovary development of Chinese sturgeon (Acipenser sinensis)

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