The Experts below are selected from a list of 33450 Experts worldwide ranked by ideXlab platform

Troy A Hornberger - One of the best experts on this subject based on the ideXlab platform.

  • the effects of krill oil on mTOR Signaling and resistance exercise a pilot study
    Journal of Nutrition and Metabolism, 2018
    Co-Authors: John I Georges, Matthew H Sharp, Ryan P Lowery, Jacob M Wilson, Martin Purpura, Troy A Hornberger, Flint Harding, James H Johnson, David Mccray Peele, Ralf Jager
    Abstract:

    Introduction. Krill oil supplementation has been shown to improve postexercise immune function; however, its effect on muscle hypertrophy is currently unknown. Therefore, the aim of present study was to investigate the ability of krill oil to stimulate mTOR Signaling and its ability to augment resistance training-induced changes in body composition and performance. Methods. C2C12 myoblasts cells were stimulated with krill oil or soy-derived phosphatidylcholine (S-PC), and then, the ratio of P-p70-389 to total p70 was used as readout for mTOR Signaling. In double-blind,placebo-controlled study, resistance trained subjects consumed either 3 g krill oil daily or placebo, and each took part in an 8-week periodized resistance training program. Body composition, maximal strength, peak power, and rate of perceived recovery were assessed collectively at the end of weeks 0 and 8. In addition, safety parameters (comprehensive metabolic panel (CMP), complete blood count (CBC), and urine analysis (UA)) and cognitive performance were measured pre- and posttesting. Results. Krill oil significantly stimulated mTOR Signaling in comparison to S-PC and control. No differences for markers on the CMP, CBC, or UA were observed. Krill oil significantly increased lean body mass from baseline (, 1.4 kg,

  • identification of mechanically regulated phosphorylation sites on tuberin tsc2 that control mechanistic target of rapamycin mTOR Signaling
    Journal of Biological Chemistry, 2017
    Co-Authors: Brittany L Jacobs, Jaesung You, Rachel M Mcnally, Kookjoo Kim, Rocky Blanco, Rachel E Privett, Troy A Hornberger
    Abstract:

    Mechanistic target of rapamycin (mTOR) Signaling is necessary to generate a mechanically induced increase in skeletal muscle mass, but the mechanism(s) through which mechanical stimuli regulate mTOR Signaling remain poorly defined. Recent studies have suggested that Ras homologue enriched in brain (Rheb), a direct activator of mTOR, and its inhibitor, the GTPase-activating protein tuberin (TSC2), may play a role in this pathway. To address this possibility, we generated inducible and skeletal muscle-specific knock-out mice for Rheb (iRhebKO) and TSC2 (iTSC2KO) and mechanically stimulated muscles from these mice with eccentric contractions (EC). As expected, the knock-out of TSC2 led to an elevation in the basal level of mTOR Signaling. Moreover, we found that the magnitude of the EC-induced activation of mTOR Signaling was significantly blunted in muscles from both inducible and skeletal muscle-specific knock-out mice for Rheb and iTSC2KO mice. Using mass spectrometry, we identified six sites on TSC2 whose phosphorylation was significantly altered by the EC treatment. Employing a transient transfection-based approach to rescue TSC2 function in muscles of the iTSC2KO mice, we demonstrated that these phosphorylation sites are required for the role that TSC2 plays in the EC-induced activation of mTOR Signaling. Importantly, however, these phosphorylation sites were not required for an insulin-induced activation of mTOR Signaling. As such, our results not only establish a critical role for Rheb and TSC2 in the mechanical activation of mTOR Signaling, but they also expose the existence of a previously unknown branch of Signaling events that can regulate the TSC2/mTOR pathway.

  • the role of mTOR Signaling in the regulation of protein synthesis and muscle mass during immobilization in mice
    Disease Models & Mechanisms, 2015
    Co-Authors: Jaesung You, Garrett B Anderson, Matthew S Dooley, Troy A Hornberger
    Abstract:

    The maintenance of skeletal muscle mass contributes substantially to health and to issues associated with the quality of life. It has been well recognized that skeletal muscle mass is regulated by mechanically induced changes in protein synthesis, and that Signaling by mTOR is necessary for an increase in protein synthesis and the hypertrophy that occurs in response to increased mechanical loading. However, the role of mTOR Signaling in the regulation of protein synthesis and muscle mass during decreased mechanical loading remains largely undefined. In order to define the role of mTOR Signaling, we employed a mouse model of hindlimb immobilization along with pharmacological, mechanical and genetic means to modulate mTOR Signaling. The results first showed that immobilization induced a decrease in the global rates of protein synthesis and muscle mass. Interestingly, immobilization also induced an increase in mTOR Signaling, eIF4F complex formation and cap-dependent translation. Blocking mTOR Signaling during immobilization with rapamycin not only impaired the increase in eIF4F complex formation, but also augmented the decreases in global protein synthesis and muscle mass. On the other hand, stimulating immobilized muscles with isometric contractions enhanced mTOR Signaling and rescued the immobilization-induced decrease in global protein synthesis through a rapamycin-sensitive mechanism that was independent of ribosome biogenesis. Unexpectedly, the effects of isometric contractions were also independent of eIF4F complex formation. Similar to isometric contractions, overexpression of Rheb in immobilized muscles enhanced mTOR Signaling, cap-dependent translation and global protein synthesis, and prevented the reduction in fiber size. Therefore, we conclude that the activation of mTOR Signaling is both necessary and sufficient to alleviate the decreases in protein synthesis and muscle mass that occur during immobilization. Furthermore, these results indicate that the activation of mTOR Signaling is a viable target for therapies that are aimed at preventing muscle atrophy during periods of mechanical unloading.

  • the role of diacylglycerol kinase ζ and phosphatidic acid in the mechanical activation of mammalian target of rapamycin mTOR Signaling and skeletal muscle hypertrophy
    Journal of Biological Chemistry, 2014
    Co-Authors: Jaesung You, John Frey, Hannah C Lincoln, Chanran Kim, Craig A Goodman, Xiaoping Zhong, Troy A Hornberger
    Abstract:

    The activation of mTOR Signaling is essential for mechanically induced changes in skeletal muscle mass, and previous studies have suggested that mechanical stimuli activate mTOR (mammalian target of rapamycin) Signaling through a phospholipase D (PLD)-dependent increase in the concentration of phosphatidic acid (PA). Consistent with this conclusion, we obtained evidence which further suggests that mechanical stimuli utilize PA as a direct upstream activator of mTOR Signaling. Unexpectedly though, we found that the activation of PLD is not necessary for the mechanically induced increases in PA or mTOR Signaling. Motivated by this observation, we performed experiments that were aimed at identifying the enzyme(s) that promotes the increase in PA. These experiments revealed that mechanical stimulation increases the concentration of diacylglycerol (DAG) and the activity of DAG kinases (DGKs) in membranous structures. Furthermore, using knock-out mice, we determined that the ζ isoform of DGK (DGKζ) is necessary for the mechanically induced increase in PA. We also determined that DGKζ significantly contributes to the mechanical activation of mTOR Signaling, and this is likely driven by an enhanced binding of PA to mTOR. Last, we found that the overexpression of DGKζ is sufficient to induce muscle fiber hypertrophy through an mTOR-dependent mechanism, and this event requires DGKζ kinase activity (i.e. the synthesis of PA). Combined, these results indicate that DGKζ, but not PLD, plays an important role in mechanically induced increases in PA and mTOR Signaling. Furthermore, this study suggests that DGKζ could be a fundamental component of the mechanism(s) through which mechanical stimuli regulate skeletal muscle mass.

  • mechanical stimulation induces mTOR Signaling via an erk independent mechanism implications for a direct activation of mTOR by phosphatidic acid
    PLOS ONE, 2012
    Co-Authors: Jaesung You, John Frey, Troy A Hornberger
    Abstract:

    Signaling by mTOR is a well-recognized component of the pathway through which mechanical signals regulate protein synthesis and muscle mass. However, the mechanisms involved in the mechanical regulation of mTOR Signaling have not been defined. Nevertheless, recent studies suggest that a mechanically-induced increase in phosphatidic acid (PA) may be involved. There is also evidence which suggests that mechanical stimuli, and PA, utilize ERK to induce mTOR Signaling. Hence, we reasoned that a mechanically-induced increase in PA might promote mTOR Signaling via an ERK-dependent mechanism. To test this, we subjected mouse skeletal muscles to mechanical stimulation in the presence or absence of a MEK/ERK inhibitor, and then measured several commonly used markers of mTOR Signaling. Transgenic mice expressing a rapamycin-resistant mutant of mTOR were also used to confirm the validity of these markers. The results demonstrated that mechanically-induced increases in p70s6k T389 and 4E-BP1 S64 phosphorylation, and unexpectedly, a loss in total 4E-BP1, were fully mTOR-dependent Signaling events. Furthermore, we determined that mechanical stimulation induced these mTOR-dependent events, and protein synthesis, through an ERK-independent mechanism. Similar to mechanical stimulation, exogenous PA also induced mTOR-dependent Signaling via an ERK-independent mechanism. Moreover, PA was able to directly activate mTOR Signaling in vitro. Combined, these results demonstrate that mechanical stimulation induces mTOR Signaling, and protein synthesis, via an ERK-independent mechanism that potentially involves a direct interaction of PA with mTOR. Furthermore, it appears that a decrease in total 4E-BP1 may be part of the mTOR-dependent mechanism through which mechanical stimuli activate protein synthesis.

Zhaoxia Wang - One of the best experts on this subject based on the ideXlab platform.

  • Chemopreventive Effect of Dietary Glutamineon Colitis-Associated Colorectal Cancer Is Associated with Modulation of the DEPTOR/mTOR Signaling Pathway
    Nutrients, 2016
    Co-Authors: Yun Tian, Keming Wang, Yingrui Fan, Yan Wang, Liqun Sun, Li Wang, Jirong Wang, Zhaoxia Wang
    Abstract:

    Glutamine plays a protective role in colitis and colitis-associated colorectal cancer (CAC); however, the protective mechanisms are largely unknown to date. DEP domain-containing mTOR-interacting protein (DEPTOR)/mammalian Target of Rapamycin (mTOR) Signaling plays an important role in carcinogenesis. The present study investigated the potential molecular mechanisms for the protective effect of glutamine in a murine model of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC. The effects of glutamine on DEPTOR/mTOR Signaling and protein light chain 3 (LC3) were evaluated. Administration of glutamine was associated with attenuated development of CAC. Increased expression of DEPTOR and decreased expressions of factors of mTOR Signaling, including phospho-mTOR, phospho-STAT3, phospho-Akt, and phospho-S6, were observed in AOM/DSS mice administered glutamine. Furthermore, oral glutamine was associated with increased LC3-II expression in AOM/DSS mice. The present study indicates that regulation of DEPTOR/mTOR Signaling may be an important mechanism for glutamine in prevention against the development of CAC. In addition, the chemopreventive effect of dietary glutamine on CAC is, at least in part, associated with the induction of autophagy.

  • chemopreventive effect of dietary glutamineon colitis associated colorectal cancer is associated with modulation of the deptor mTOR Signaling pathway
    Nutrients, 2016
    Co-Authors: Yun Tian, Keming Wang, Yingrui Fan, Yan Wang, Liqun Sun, Li Wang, Jirong Wang, Zhaoxia Wang
    Abstract:

    Glutamine plays a protective role in colitis and colitis-associated colorectal cancer (CAC); however, the protective mechanisms are largely unknown to date. DEP domain-containing mTOR-interacting protein (DEPTOR)/mammalian Target of Rapamycin (mTOR) Signaling plays an important role in carcinogenesis. The present study investigated the potential molecular mechanisms for the protective effect of glutamine in a murine model of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC. The effects of glutamine on DEPTOR/mTOR Signaling and protein light chain 3 (LC3) were evaluated. Administration of glutamine was associated with attenuated development of CAC. Increased expression of DEPTOR and decreased expressions of factors of mTOR Signaling, including phospho-mTOR, phospho-STAT3, phospho-Akt, and phospho-S6, were observed in AOM/DSS mice administered glutamine. Furthermore, oral glutamine was associated with increased LC3-II expression in AOM/DSS mice. The present study indicates that regulation of DEPTOR/mTOR Signaling may be an important mechanism for glutamine in prevention against the development of CAC. In addition, the chemopreventive effect of dietary glutamine on CAC is, at least in part, associated with the induction of autophagy.

Yun Tian - One of the best experts on this subject based on the ideXlab platform.

  • Chemopreventive Effect of Dietary Glutamineon Colitis-Associated Colorectal Cancer Is Associated with Modulation of the DEPTOR/mTOR Signaling Pathway
    Nutrients, 2016
    Co-Authors: Yun Tian, Keming Wang, Yingrui Fan, Yan Wang, Liqun Sun, Li Wang, Jirong Wang, Zhaoxia Wang
    Abstract:

    Glutamine plays a protective role in colitis and colitis-associated colorectal cancer (CAC); however, the protective mechanisms are largely unknown to date. DEP domain-containing mTOR-interacting protein (DEPTOR)/mammalian Target of Rapamycin (mTOR) Signaling plays an important role in carcinogenesis. The present study investigated the potential molecular mechanisms for the protective effect of glutamine in a murine model of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC. The effects of glutamine on DEPTOR/mTOR Signaling and protein light chain 3 (LC3) were evaluated. Administration of glutamine was associated with attenuated development of CAC. Increased expression of DEPTOR and decreased expressions of factors of mTOR Signaling, including phospho-mTOR, phospho-STAT3, phospho-Akt, and phospho-S6, were observed in AOM/DSS mice administered glutamine. Furthermore, oral glutamine was associated with increased LC3-II expression in AOM/DSS mice. The present study indicates that regulation of DEPTOR/mTOR Signaling may be an important mechanism for glutamine in prevention against the development of CAC. In addition, the chemopreventive effect of dietary glutamine on CAC is, at least in part, associated with the induction of autophagy.

  • chemopreventive effect of dietary glutamineon colitis associated colorectal cancer is associated with modulation of the deptor mTOR Signaling pathway
    Nutrients, 2016
    Co-Authors: Yun Tian, Keming Wang, Yingrui Fan, Yan Wang, Liqun Sun, Li Wang, Jirong Wang, Zhaoxia Wang
    Abstract:

    Glutamine plays a protective role in colitis and colitis-associated colorectal cancer (CAC); however, the protective mechanisms are largely unknown to date. DEP domain-containing mTOR-interacting protein (DEPTOR)/mammalian Target of Rapamycin (mTOR) Signaling plays an important role in carcinogenesis. The present study investigated the potential molecular mechanisms for the protective effect of glutamine in a murine model of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC. The effects of glutamine on DEPTOR/mTOR Signaling and protein light chain 3 (LC3) were evaluated. Administration of glutamine was associated with attenuated development of CAC. Increased expression of DEPTOR and decreased expressions of factors of mTOR Signaling, including phospho-mTOR, phospho-STAT3, phospho-Akt, and phospho-S6, were observed in AOM/DSS mice administered glutamine. Furthermore, oral glutamine was associated with increased LC3-II expression in AOM/DSS mice. The present study indicates that regulation of DEPTOR/mTOR Signaling may be an important mechanism for glutamine in prevention against the development of CAC. In addition, the chemopreventive effect of dietary glutamine on CAC is, at least in part, associated with the induction of autophagy.

Jaesung You - One of the best experts on this subject based on the ideXlab platform.

  • identification of mechanically regulated phosphorylation sites on tuberin tsc2 that control mechanistic target of rapamycin mTOR Signaling
    Journal of Biological Chemistry, 2017
    Co-Authors: Brittany L Jacobs, Jaesung You, Rachel M Mcnally, Kookjoo Kim, Rocky Blanco, Rachel E Privett, Troy A Hornberger
    Abstract:

    Mechanistic target of rapamycin (mTOR) Signaling is necessary to generate a mechanically induced increase in skeletal muscle mass, but the mechanism(s) through which mechanical stimuli regulate mTOR Signaling remain poorly defined. Recent studies have suggested that Ras homologue enriched in brain (Rheb), a direct activator of mTOR, and its inhibitor, the GTPase-activating protein tuberin (TSC2), may play a role in this pathway. To address this possibility, we generated inducible and skeletal muscle-specific knock-out mice for Rheb (iRhebKO) and TSC2 (iTSC2KO) and mechanically stimulated muscles from these mice with eccentric contractions (EC). As expected, the knock-out of TSC2 led to an elevation in the basal level of mTOR Signaling. Moreover, we found that the magnitude of the EC-induced activation of mTOR Signaling was significantly blunted in muscles from both inducible and skeletal muscle-specific knock-out mice for Rheb and iTSC2KO mice. Using mass spectrometry, we identified six sites on TSC2 whose phosphorylation was significantly altered by the EC treatment. Employing a transient transfection-based approach to rescue TSC2 function in muscles of the iTSC2KO mice, we demonstrated that these phosphorylation sites are required for the role that TSC2 plays in the EC-induced activation of mTOR Signaling. Importantly, however, these phosphorylation sites were not required for an insulin-induced activation of mTOR Signaling. As such, our results not only establish a critical role for Rheb and TSC2 in the mechanical activation of mTOR Signaling, but they also expose the existence of a previously unknown branch of Signaling events that can regulate the TSC2/mTOR pathway.

  • the role of mTOR Signaling in the regulation of protein synthesis and muscle mass during immobilization in mice
    Disease Models & Mechanisms, 2015
    Co-Authors: Jaesung You, Garrett B Anderson, Matthew S Dooley, Troy A Hornberger
    Abstract:

    The maintenance of skeletal muscle mass contributes substantially to health and to issues associated with the quality of life. It has been well recognized that skeletal muscle mass is regulated by mechanically induced changes in protein synthesis, and that Signaling by mTOR is necessary for an increase in protein synthesis and the hypertrophy that occurs in response to increased mechanical loading. However, the role of mTOR Signaling in the regulation of protein synthesis and muscle mass during decreased mechanical loading remains largely undefined. In order to define the role of mTOR Signaling, we employed a mouse model of hindlimb immobilization along with pharmacological, mechanical and genetic means to modulate mTOR Signaling. The results first showed that immobilization induced a decrease in the global rates of protein synthesis and muscle mass. Interestingly, immobilization also induced an increase in mTOR Signaling, eIF4F complex formation and cap-dependent translation. Blocking mTOR Signaling during immobilization with rapamycin not only impaired the increase in eIF4F complex formation, but also augmented the decreases in global protein synthesis and muscle mass. On the other hand, stimulating immobilized muscles with isometric contractions enhanced mTOR Signaling and rescued the immobilization-induced decrease in global protein synthesis through a rapamycin-sensitive mechanism that was independent of ribosome biogenesis. Unexpectedly, the effects of isometric contractions were also independent of eIF4F complex formation. Similar to isometric contractions, overexpression of Rheb in immobilized muscles enhanced mTOR Signaling, cap-dependent translation and global protein synthesis, and prevented the reduction in fiber size. Therefore, we conclude that the activation of mTOR Signaling is both necessary and sufficient to alleviate the decreases in protein synthesis and muscle mass that occur during immobilization. Furthermore, these results indicate that the activation of mTOR Signaling is a viable target for therapies that are aimed at preventing muscle atrophy during periods of mechanical unloading.

  • the role of diacylglycerol kinase ζ and phosphatidic acid in the mechanical activation of mammalian target of rapamycin mTOR Signaling and skeletal muscle hypertrophy
    Journal of Biological Chemistry, 2014
    Co-Authors: Jaesung You, John Frey, Hannah C Lincoln, Chanran Kim, Craig A Goodman, Xiaoping Zhong, Troy A Hornberger
    Abstract:

    The activation of mTOR Signaling is essential for mechanically induced changes in skeletal muscle mass, and previous studies have suggested that mechanical stimuli activate mTOR (mammalian target of rapamycin) Signaling through a phospholipase D (PLD)-dependent increase in the concentration of phosphatidic acid (PA). Consistent with this conclusion, we obtained evidence which further suggests that mechanical stimuli utilize PA as a direct upstream activator of mTOR Signaling. Unexpectedly though, we found that the activation of PLD is not necessary for the mechanically induced increases in PA or mTOR Signaling. Motivated by this observation, we performed experiments that were aimed at identifying the enzyme(s) that promotes the increase in PA. These experiments revealed that mechanical stimulation increases the concentration of diacylglycerol (DAG) and the activity of DAG kinases (DGKs) in membranous structures. Furthermore, using knock-out mice, we determined that the ζ isoform of DGK (DGKζ) is necessary for the mechanically induced increase in PA. We also determined that DGKζ significantly contributes to the mechanical activation of mTOR Signaling, and this is likely driven by an enhanced binding of PA to mTOR. Last, we found that the overexpression of DGKζ is sufficient to induce muscle fiber hypertrophy through an mTOR-dependent mechanism, and this event requires DGKζ kinase activity (i.e. the synthesis of PA). Combined, these results indicate that DGKζ, but not PLD, plays an important role in mechanically induced increases in PA and mTOR Signaling. Furthermore, this study suggests that DGKζ could be a fundamental component of the mechanism(s) through which mechanical stimuli regulate skeletal muscle mass.

  • mechanical stimulation induces mTOR Signaling via an erk independent mechanism implications for a direct activation of mTOR by phosphatidic acid
    PLOS ONE, 2012
    Co-Authors: Jaesung You, John Frey, Troy A Hornberger
    Abstract:

    Signaling by mTOR is a well-recognized component of the pathway through which mechanical signals regulate protein synthesis and muscle mass. However, the mechanisms involved in the mechanical regulation of mTOR Signaling have not been defined. Nevertheless, recent studies suggest that a mechanically-induced increase in phosphatidic acid (PA) may be involved. There is also evidence which suggests that mechanical stimuli, and PA, utilize ERK to induce mTOR Signaling. Hence, we reasoned that a mechanically-induced increase in PA might promote mTOR Signaling via an ERK-dependent mechanism. To test this, we subjected mouse skeletal muscles to mechanical stimulation in the presence or absence of a MEK/ERK inhibitor, and then measured several commonly used markers of mTOR Signaling. Transgenic mice expressing a rapamycin-resistant mutant of mTOR were also used to confirm the validity of these markers. The results demonstrated that mechanically-induced increases in p70s6k T389 and 4E-BP1 S64 phosphorylation, and unexpectedly, a loss in total 4E-BP1, were fully mTOR-dependent Signaling events. Furthermore, we determined that mechanical stimulation induced these mTOR-dependent events, and protein synthesis, through an ERK-independent mechanism. Similar to mechanical stimulation, exogenous PA also induced mTOR-dependent Signaling via an ERK-independent mechanism. Moreover, PA was able to directly activate mTOR Signaling in vitro. Combined, these results demonstrate that mechanical stimulation induces mTOR Signaling, and protein synthesis, via an ERK-independent mechanism that potentially involves a direct interaction of PA with mTOR. Furthermore, it appears that a decrease in total 4E-BP1 may be part of the mTOR-dependent mechanism through which mechanical stimuli activate protein synthesis.

Keming Wang - One of the best experts on this subject based on the ideXlab platform.

  • Chemopreventive Effect of Dietary Glutamineon Colitis-Associated Colorectal Cancer Is Associated with Modulation of the DEPTOR/mTOR Signaling Pathway
    Nutrients, 2016
    Co-Authors: Yun Tian, Keming Wang, Yingrui Fan, Yan Wang, Liqun Sun, Li Wang, Jirong Wang, Zhaoxia Wang
    Abstract:

    Glutamine plays a protective role in colitis and colitis-associated colorectal cancer (CAC); however, the protective mechanisms are largely unknown to date. DEP domain-containing mTOR-interacting protein (DEPTOR)/mammalian Target of Rapamycin (mTOR) Signaling plays an important role in carcinogenesis. The present study investigated the potential molecular mechanisms for the protective effect of glutamine in a murine model of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC. The effects of glutamine on DEPTOR/mTOR Signaling and protein light chain 3 (LC3) were evaluated. Administration of glutamine was associated with attenuated development of CAC. Increased expression of DEPTOR and decreased expressions of factors of mTOR Signaling, including phospho-mTOR, phospho-STAT3, phospho-Akt, and phospho-S6, were observed in AOM/DSS mice administered glutamine. Furthermore, oral glutamine was associated with increased LC3-II expression in AOM/DSS mice. The present study indicates that regulation of DEPTOR/mTOR Signaling may be an important mechanism for glutamine in prevention against the development of CAC. In addition, the chemopreventive effect of dietary glutamine on CAC is, at least in part, associated with the induction of autophagy.

  • chemopreventive effect of dietary glutamineon colitis associated colorectal cancer is associated with modulation of the deptor mTOR Signaling pathway
    Nutrients, 2016
    Co-Authors: Yun Tian, Keming Wang, Yingrui Fan, Yan Wang, Liqun Sun, Li Wang, Jirong Wang, Zhaoxia Wang
    Abstract:

    Glutamine plays a protective role in colitis and colitis-associated colorectal cancer (CAC); however, the protective mechanisms are largely unknown to date. DEP domain-containing mTOR-interacting protein (DEPTOR)/mammalian Target of Rapamycin (mTOR) Signaling plays an important role in carcinogenesis. The present study investigated the potential molecular mechanisms for the protective effect of glutamine in a murine model of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC. The effects of glutamine on DEPTOR/mTOR Signaling and protein light chain 3 (LC3) were evaluated. Administration of glutamine was associated with attenuated development of CAC. Increased expression of DEPTOR and decreased expressions of factors of mTOR Signaling, including phospho-mTOR, phospho-STAT3, phospho-Akt, and phospho-S6, were observed in AOM/DSS mice administered glutamine. Furthermore, oral glutamine was associated with increased LC3-II expression in AOM/DSS mice. The present study indicates that regulation of DEPTOR/mTOR Signaling may be an important mechanism for glutamine in prevention against the development of CAC. In addition, the chemopreventive effect of dietary glutamine on CAC is, at least in part, associated with the induction of autophagy.