Adenosine Metabolism in the Cerebral Cortex from Several Mice Models during Aging

Sánchez-Melgar, Alejandro; Albasanz, José Luís; Pallàs, Mercè; Martı́n, Mairena

doi:10.3390/ijms21197300

Cited by 13 publications

(7 citation statements)

References 104 publications

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“…Elevated levels of brain cholesterol in the plasma membrane could increase membrane rigidity, which might affect the neurotransmission through a reduction of membrane-associated proteins movement (i.e., neurotransmitters receptors) from and to the synapsis. Notably, we previously found a significant age-dependent reduction in adenosine [ 27 ] and metabotropic glutamate receptors [ 28 ] together with their corresponding endogenous ligand [ 26 ] in SAMP8 mice. In addition, cholesterol modulates adenosine A 2A receptors expressed on the cell surface of in vitro glial cells [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…The effects and mechanisms of resveratrol on aging and age-related diseases, including neurodegenerative disorders, have been reviewed elsewhere [ 24 , 25 ]. Our previous work revealed that RSV supplementation in SAMP8 mice was able to modulate adenosine metabolism [ 26 ] and to modulate and reverse the age-related effect on adenosine-mediated signalling [ 27 ], and that metabotropic glutamate receptors are differently modulated by RSV, depending on age [ 28 ]. Moreover, we have described that a high-fat diet (HFD) and RSV diet modulate adenosinergic signalling in SAMP8 mice by increasing adenosine A 2 receptors and 5′-NT activity [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

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Neuroprotective Effects of Resveratrol by Modifying Cholesterol Metabolism and Aβ Processing in SAMP8 Mice

Sánchez-Melgar

Izquierdo-Ramírez

Griñán-Ferré

et al. 2022

IJMS

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Cholesterol metabolism seems dysregulated and linked to amyloid-β (Aβ) formation in neurodegeneration, but the underlying mechanisms are poorly known. Resveratrol (RSV) is a polyphenol with antioxidant activity and neuroprotective properties. Here, we analyzed the effect of age and RSV supplementation on cholesterol metabolism in the brain and blood serum, and its potential link to Aβ processing, in SAMP8 mice—an animal model of aging and Alzheimer’s disease. In the brain, our results revealed an age-related increase in ApoE and unesterified cholesterol in the plasma membrane whereas LDL receptor, HMG-CoA reductase, HMG-CoA-C1 synthase, and ABCA1 transporter remained unaltered. Furthermore, BACE-1 and APP gene expression was decreased. This dysregulation could be involved in the amyloidogenic processing pathway of APP towards Aβ formation. In turn, RSV exhibited an age-dependent effect. While levels of unesterified cholesterol in the plasma membrane were not affected by RSV, several participants in cholesterol uptake, release, and de novo synthesis differed, depending on age. Thus, RSV supplementation exhibited a different neuroprotective effect acting on Aβ processing or cholesterol metabolism in the brain at earlier or later ages, respectively. In blood serum, HDL lipoprotein and free cholesterol were increased by age, whereas VLDL and LDL lipoproteins remained unaltered. Again, the protective effect of RSV by decreasing the LDL or increasing the HDL levels also seems to depend on the intervention’s moment. In conclusion, age is a prominent factor for cholesterol metabolism dysregulation in the brain of SAMP8 mice and influences the protective effects of RSV through cholesterol metabolism and Aβ processing.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effects of Resveratrol by Modifying Cholesterol Metabolism and Aβ Processing in SAMP8 Mice

Sánchez-Melgar

Izquierdo-Ramírez

Griñán-Ferré

et al. 2022

IJMS

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“…All samples were run in duplicate. Sample values were obtained by interpolation in an inosine standard curve performed in parallel on the same plate as previously described ( 46 ).…”

Section: Methodsmentioning

confidence: 99%

Resveratrol enhances A1 and hinders A2A adenosine receptors signaling in both HeLa and SH-SY5Y cells: Potential mechanism of its antitumoral action

Muñoz-López

Sánchez-Melgar²,

Martı́n³

et al. 2022

Front. Endocrinol.

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Despite great efforts, effective treatment against cancer has not yet been found. However, natural compounds such as the polyphenol resveratrol have emerged as promising preventive agent in cancer therapy. The mode of action of resveratrol is still poorly understood, but it can modulate many signaling pathways related to the initiation and progression of cancer. Adenosinergic signaling may be involved in the antitumoral action of resveratrol since resveratrol binds to the orthosteric binding site of adenosine A2A receptors and acts as a non-selective agonist for adenosine receptors. In the present study, we measured the impact of resveratrol treatment on different adenosinergic pathway components (i.e. adenosine receptors levels, 5’-nucleotidase, adenosine deaminase, and adenylyl cyclase activities, protein kinase A levels, intracellular adenosine and other related metabolites levels) and cell viability and proliferation in HeLa and SH-SY5Y cell lines. Results revealed changes leading to turning off cAMP signaling such as decreased levels of A2A receptors and reduced adenylyl cyclase activation, increased levels of A1 receptors and increased adenylyl cyclase inhibition, and lower levels of PKA. All these changes could contribute to the antitumoral action of resveratrol. Interestingly, these effects were almost identical in HeLa and SH-SY5Y cells suggesting that resveratrol enhances A1 and hinders A2A adenosine receptors signaling as part of a potential mechanism of antitumoral action.

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“…Therefore, 100 µM theacrine and 1 µM CGS21680 were used in the following experiments. Adenosine mediates its action via the adenosine 2A receptor coupled primarily to the activation of cAMP, which in turn activates AMP-activated protein kinase (AMPK) [21]. To inspect whether theacrine is an effective antagonist of the adenosine 2A receptor, CGS21680 was employed to activate the adenosine 2A receptor by detecting the level of AMPK phosphorylation (P-AMPK/AMPK) in MCF-7 cells with or without the theacrine supplement (Figure 3).…”

Section: Molecular Modeling Of Theacrine Caffeine and Adenosine Docki...mentioning

confidence: 99%

Attenuation of Tumor Development in Mammary Carcinoma Rats by Theacrine, an Antagonist of Adenosine 2A Receptor

et al. 2021

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Caffeine has been reported to induce anti-tumor immunity for attenuating breast cancer by blocking the adenosine 2A receptor. Molecular modeling showed that theacrine, a purine alkaloid structurally similar to caffeine, might be an antagonist of the adenosine 2A receptor equivalent to or more effective than caffeine. Theacrine was further demonstrated to be an effective antagonist of the adenosine 2A receptor as its concurrent supplementation significantly reduced the elevation of AMPK phosphorylation level in MCF-7 human breast cells induced by CGS21680, an agonist of adenosine 2A receptors. In an animal model, the development of mammary carcinoma induced by 7,12-Dimethylbenz[a]anthracene in Sprague–Dawley rats could be attenuated by daily supplement of theacrine of 50 or 100 mg/kg body weight. Both expression levels of cleaved-caspase-3/pro-caspase-3 and granzyme B in tumor tissues were significantly elevated when theacrine was supplemented, indicating the induction of programmed cell death in tumor cells might be involved in the attenuation of mammary carcinoma. Similar to the caffeine, significant elevation of interferon-γ and tumor necrosis factor-α was observed in the serum and tumor tissues of rats after the theacrine supplement of 50 mg/kg body weight. Taken together, theacrine is an effective antagonist of adenosine 2A receptors and possesses great potential to be used to attenuate breast cancer.

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Adenosine Metabolism in the Cerebral Cortex from Several Mice Models during Aging

Cited by 13 publications

References 104 publications

Neuroprotective Effects of Resveratrol by Modifying Cholesterol Metabolism and Aβ Processing in SAMP8 Mice

Neuroprotective Effects of Resveratrol by Modifying Cholesterol Metabolism and Aβ Processing in SAMP8 Mice

Resveratrol enhances A1 and hinders A2A adenosine receptors signaling in both HeLa and SH-SY5Y cells: Potential mechanism of its antitumoral action

Attenuation of Tumor Development in Mammary Carcinoma Rats by Theacrine, an Antagonist of Adenosine 2A Receptor

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