Weighing on autophagy

Coupé, Bérengère; Bouret, Sébastien G.

doi:10.4161/cc.20046

Cited by 4 publications

(1 citation statement)

References 11 publications

(13 reference statements)

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“…This process replenishes pools of cellular precursors in response to pressure (Ryter et al, 2013). Autophagy, which is a mechanism for the degradation of cellular components that has come to prominence for its involvement in a number of important diseases (such as obesity, cancer, and neurodegenerative disorders), has been revealed to be critical to the regulation of energy balance in the brain (Choo et al, 2010;Coupe and Bouret, 2012). Autophagy might also participate directly in the degradation of glycogen, lipid and protein to produce ATP to meet celluar demand (Mizushima, 2007;Kovsan et al, 2009;Kim and Lee, 2014).…”

Section: Hamartin-mediated Endogenous Neuroprotectionmentioning

confidence: 99%

Hamartin: An Endogenous Neuroprotective Molecule Induced by Hypoxic Preconditioning

Ren

Stone

et al. 2020

Front. Genet.

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Hypoxic/ischemic preconditioning (HPC/IPC) is an innate neuroprotective mechanism in which a number of endogenous molecules are known to be involved. Tuberous sclerosis complex 1 (TSC1), also known as hamartin, is thought to be one such molecule. It is also known that hamartin is involved as a target in the rapamycin (mTOR) signaling pathway, which functions to integrate a variety of environmental triggers in order to exert control over cellular metabolism and homeostasis. Understanding the role of hamartin in ischemic/hypoxic neuroprotection will provide a novel target for the treatment of hypoxic-ischemic disease. Therefore, the proposed molecular mechanisms of this neuroprotective role and its preconditions are reviewed in this paper, with emphases on the mTOR pathway and the relationship between the expression of hamartin and DNA methylation.

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Section: Hamartin-mediated Endogenous Neuroprotectionmentioning

confidence: 99%

Hamartin: An Endogenous Neuroprotective Molecule Induced by Hypoxic Preconditioning

Ren

Stone

et al. 2020

Front. Genet.

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Rapamycin Ameliorates Age-Dependent Obesity Associated with Increased mTOR Signaling in Hypothalamic POMC Neurons

Yang

Tien

Boddupalli

et al. 2012

Neuron

197

155

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Summary The prevalence of obesity in older people is the leading cause of metabolic syndromes. Central neurons serving as homeostatic sensors for bodyweight control include hypothalamic neurons that express pro-opiomelanocortin (POMC) or neuropeptide-Y (NPY) and agouti-related protein (AgRP). Here we report an age-dependent increase of mammalian target of rapamycin (mTOR) signaling in POMC neurons that elevates the ATP-sensitive potassium (KATP) channel activity cell-autonomously to silence POMC neurons. Systemic or intracerebral administration of the mTOR inhibitor rapamycin causes weight loss in old mice. Intracerebral rapamycin infusion into old mice enhances the excitability and neurite projection of POMC neurons, thereby causing a reduction of food intake and bodyweight. Conversely, young mice lacking the mTOR negative regulator TSC1 in POMC neurons, but not those lacking TSC1 in NPY/AgRP neurons, were obese. Our study reveals that an increase in mTOR signaling in hypothalamic POMC neurons contributes to age-dependent obesity.

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Possible Involvement of DNA Methylation in TSC1 Gene Expression in Neuroprotection Induced by Hypoxic Preconditioning

Xie

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. It has been reported that ischemia and ischemic preconditioning (IPC) have different effects on the expression of tuberous sclerosis complex 1 (TSC1), which may contribute to the tolerance to ischemia/hypoxia with the increase of autophagy. The mechanisms of TSC1 differential expression are still unclear under ischemia/IPC conditions in hippocampal Cornu Ammon 1 (CA1) and Cornu Ammon 3 (CA3) area neuronal cells. While we have shown that 5-Aza-CdR, a DNA methyltransferase inhibitor, can upregulate TSC1 and increase hypoxic tolerance by autophagy in vivo and in vitro, in this study, we examined whether DNA methylation was involved in the differential expression of TSC1 in the CA1 and CA3 regions induced by hypoxic preconditioning (HPC). Methods. Level of rapamycin (mTOR) autophagy, a downstream molecular pathway of TSC1/TSC2 complex, was detected in HPC mouse hippocampal CA1 and CA3 areas as well as in the HPC model of mouse hippocampal HT22 cells. DNA methylation level of TSC1 promoter (-720 bp~ -360 bp) was determined in CA1 and CA3 areas by bisulfite-modified DNA sequencing (BMDS). At the same time, autophagy was detected in HT22 cells transfected with GFP-LC3 plasmid. The role of TSC1 in neuroprotection was measured by cell viability and apoptosis, and the role of TSC1 in metabolism was checked by ATP assay and ROS assay in HT22 cells that overexpressed/knocked down TSC1. Results. HPC upregulated the expression of TSC1, downregulated the level of P-mTOR (Ser2448) and P-p70S6K (Thr389), and enhanced the activity of autophagy in both in vivo and in vitro. The increased expression of TSC1 in HPC may depend on its DNA hypomethylation in the promoter region in vivo. HPC also could reduce energy consumption in HT22 cells. Overexpression and knockdown of TSC1 can affect cell viability, cell apoptosis, and metabolism in HT22 cells exposed to hypoxia. Conclusion. TSC1 expression induced by HPC may relate to the downregulation of its DNA methylation level with the increase of autophagy and the decrease of energy demand.

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Weighing on autophagy

Cited by 4 publications

References 11 publications

Hamartin: An Endogenous Neuroprotective Molecule Induced by Hypoxic Preconditioning

Hamartin: An Endogenous Neuroprotective Molecule Induced by Hypoxic Preconditioning

Rapamycin Ameliorates Age-Dependent Obesity Associated with Increased mTOR Signaling in Hypothalamic POMC Neurons

Possible Involvement of DNA Methylation in TSC1 Gene Expression in Neuroprotection Induced by Hypoxic Preconditioning

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