The putative leucine sensor Sestrin2 is hyperphosphorylated by acute resistance exercise but not protein ingestion in human skeletal muscle

Zeng, Nina; D’Souza, Randall F.; Sorrenson, Brie; Merry, Troy L.; Barnett, Matthew P. G.; Mitchell, Cameron J.; Cameron‐Smith, David

doi:10.1007/s00421-018-3853-8

Cited by 9 publications

(5 citation statements)

References 58 publications

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“…Both Sesn1 and 2 levels are significantly decreased in patients with sarcopenic muscle disease (Rajan et al, 2020). Resistant exercise but not dietary protein increased the Sesn2 level and its phosphorylation in the skeletal muscle of elderly humans (Zeng et al, 2018b) and aged mice (Lenhare et al, 2017). The following are examples in the way Sestrins are involved with symptoms of aging.…”

Section: Sestrins In Environmental Stress and Agingmentioning

confidence: 98%

“…ULK1 phosphorylates T232/S249/S279 residues of Sestrin2 which inhibits Sestrin2's binding with leucine in high nutrient condition (Kimball et al, 2016). Exercise increases the same phosphorylation profile of Sestrin2 and improves skeletal muscle metabolism (Zeng et al, 2017(Zeng et al, , 2018b. ULK1 also phosphorylates S73 and S254 to activate the autophagic clearance of mitochondria in response to copperinduced oxidative stress (Kim H. et al, 2020).…”

Section: Introduction Of Sestrinsmentioning

confidence: 99%

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SESTRINs: Emerging Dynamic Stress-Sensors in Metabolic and Environmental Health

Fay

Cyuzuzo

et al. 2020

Front. Cell Dev. Biol.

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Proper timely management of various external and internal stresses is critical for metabolic and redox homeostasis in mammals. In particular, dysregulation of mechanistic target of rapamycin complex (mTORC) triggered from metabolic stress and accumulation of reactive oxygen species (ROS) generated from environmental and genotoxic stress are well-known culprits leading to chronic metabolic disease conditions in humans. Sestrins are one of the metabolic and environmental stress-responsive groups of proteins, which solely have the ability to regulate both mTORC activity and ROS levels in cells, tissues and organs. While Sestrins are originally reported as one of several p53 target genes, recent studies have further delineated the roles of this group of stress-sensing proteins in the regulation of insulin sensitivity, glucose and fat metabolism, and redox-function in metabolic disease and aging. In this review, we discuss recent studies that investigated and manipulated Sestrins-mediated stress signaling pathways in metabolic and environmental health. Sestrins as an emerging dynamic group of stress-sensor proteins are drawing a spotlight as a preventive or therapeutic mechanism in both metabolic stress-associated pathologies and aging processes at the same time.

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Section: Sestrins In Environmental Stress and Agingmentioning

confidence: 98%

Section: Introduction Of Sestrinsmentioning

confidence: 99%

SESTRINs: Emerging Dynamic Stress-Sensors in Metabolic and Environmental Health

Fay

Cyuzuzo

et al. 2020

Front. Cell Dev. Biol.

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“…The basal protein content of the amino acid sensor Sestrin2 did not significantly differ between groups and is consistent with previous findings [ 81 ]. Acute RE, but not protein ingestion, appears to hyperphosphorylate Sestrin2 [ 82 , 83 ], strengthening its association with GATOR2 and inhibiting mTORC1 activation [ 84 ]. Previous studies have quantified Sestrin2 phosphorylation using the electrophoretic mobility shift method [ 81 , 82 , 83 , 84 ].…”

Section: Discussionmentioning

confidence: 99%

“…Acute RE, but not protein ingestion, appears to hyperphosphorylate Sestrin2 [ 82 , 83 ], strengthening its association with GATOR2 and inhibiting mTORC1 activation [ 84 ]. Previous studies have quantified Sestrin2 phosphorylation using the electrophoretic mobility shift method [ 81 , 82 , 83 , 84 ]. Had we implemented this, we may have gained further insights given the purported effects of leucine on the Sestrin2-GATOR2 interaction [ 85 ].…”

Section: Discussionmentioning

confidence: 99%

Novel Essential Amino Acid Supplements Following Resistance Exercise Induce Aminoacidemia and Enhance Anabolic Signaling Irrespective of Age: A Proof-of-Concept Trial

et al. 2020

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We investigated the effects of ingesting a leucine-enriched essential amino acid (EAA) gel alone or combined with resistance exercise (RE) versus RE alone (control) on plasma aminoacidemia and intramyocellular anabolic signaling in healthy younger (28 ± 4 years) and older (71 ± 3 years) adults. Blood samples were obtained throughout the three trials, while muscle biopsies were collected in the postabsorptive state and 2 h following RE, following the consumption of two 50 mL EAA gels (40% leucine, 15 g total EAA), and following RE with EAA (combination (COM)). Protein content and the phosphorylation status of key anabolic signaling proteins were determined via immunoblotting. Irrespective of age, during EAA and COM peak leucinemia (younger: 454 ± 32 µM and 537 ± 111 µM; older: 417 ± 99 µM and 553 ± 136 µM) occurred ~60–120 min post-ingestion (younger: 66 ± 6 min and 120 ± 60 min; older: 90 ± 13 min and 78 ± 12 min). In the pooled sample, the area under the curve for plasma leucine and the sum of branched-chain amino acids was significantly greater in EAA and COM compared with RE. For intramyocellular signaling, significant main effects were found for condition (mTOR (Ser2481), rpS6 (Ser235/236)) and age (S6K1 (Thr421/Ser424), 4E-BP1 (Thr37/46)) in age group analyses. The phosphorylation of rpS6 was of similar magnitude (~8-fold) in pooled and age group data 2 h following COM. Our findings suggest that a gel-based, leucine-enriched EAA supplement is associated with aminoacidemia and a muscle anabolic signaling response, thus representing an effective means of stimulating muscle protein anabolism in younger and older adults following EAA and COM.

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“…Moreover, hypoxia, stress, or inflammation will activate the mTORC1. Sestrin2, as a leucine sensor, is significantly increased in mTORC1 activation [ 23 – 25 ]. It was reported that hypoxia, oxidative stress, and inflammation recurred in OSA [ 26 – 28 ].…”

Section: Discussionmentioning

confidence: 99%

Investigation of Urinary Sestrin2 in Patients with Obstructive Sleep Apnea

Bai

Sun²,

Zhai

et al. 2019

Lung

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Background Obstructive sleep apnea (OSA) is a disease seriously threatening individual health, which results in serious complications such as hypertension and stroke. These complications are associated with oxidative stress triggered by intermittent hypoxia in OSA. Sestrin2 is a crucial factor involved in oxidative stress. The goal of this study was to investigate if a relationship exists between OSA and Sestrin2. Methods We prospectively enrolled 71 subjects, and 16 patients of them with severe OSA completed 4 weeks of nasal continuous positive airway pressure (nCPAP) therapy. We measured and compared the concentration of Sestrin2 in the urine of all subjects, as well as the changes between before and after nCPAP treatment. Additionally, the correlation between Sestrin2 and sleep parameters was analyzed, and the multiple linear regression analysis with stepwise selection was performed to explore the relationship between Sestrin2 and various factors. Results A total of 71 subjects were enrolled and divided into two groups: OSA group ( n = 41), control group ( n = 30). The level of urinary Sestrin2 in OSA patients was significantly higher than that of the control group, and increased with the severity of OSA, while it reduced after nCPAP treatment. Additionally, Sestrin2 was positively correlated with apnea/hypopnea index (AHI), oxygen desaturation index, oxygen saturation < 90% percentage of recording time spent (PRTS) and high-density lipoprotein (HDL), while negatively correlated with the lowest oxygen saturation. Importantly, Sestrin2 was independently associated with AHI, oxygen saturation < 90% PRTS and HDL. Conclusions Urinary Sestrin2 is involved in OSA, and is a paramount marker of OSA severity.

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The putative leucine sensor Sestrin2 is hyperphosphorylated by acute resistance exercise but not protein ingestion in human skeletal muscle

Abstract: Dietary protein ingestion did not affect the signalling by the family of Sestrins. With RE, Sestrin2 was hyperphosphorylated, with no further evidence of a relationship to AMPK signalling.

Cited by 9 publications

References 58 publications

SESTRINs: Emerging Dynamic Stress-Sensors in Metabolic and Environmental Health

SESTRINs: Emerging Dynamic Stress-Sensors in Metabolic and Environmental Health

Novel Essential Amino Acid Supplements Following Resistance Exercise Induce Aminoacidemia and Enhance Anabolic Signaling Irrespective of Age: A Proof-of-Concept Trial

Investigation of Urinary Sestrin2 in Patients with Obstructive Sleep Apnea

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