ATF4-Mediated Upregulation of REDD1 and Sestrin2 Suppresses mTORC1 Activity during Prolonged Leucine Deprivation.

Background: The protein kinase target of rapamycin (mTOR) in complex 1 (mTORC1) is activated by amino acids and in turn upregulates anabolic processes. Under nutrient-deficient conditions, e.g.

Suppression of p16 Induces mTORC1-Mediated Nucleotide Metabolic Reprogramming.

Reprogrammed metabolism and cell cycle dysregulation are two cancer hallmarks. p16 is a cell cycle inhibitor and tumor suppressor that is upregulated during oncogene-induced senescence (OIS). Loss of p16 allows for uninhibited cell cycle progression, bypass of OIS, and tumorigenesis.

Evidence for a role for Sestrin1 in mediating leucine-induced activation of mTORC1 in skeletal muscle.

Previous studies established that leucine stimulates protein synthesis in skeletal muscle to the same extent as a complete mixture of amino acids, and the effect occurs through activation of the mechanistic target of rapamycin in complex 1 (mTORC1). Recent studies using cells in culture showed that the Sestrins bind leucine and are required for leucine-dependent activation of mTORC1. However, the role they play in mediating leucine-dependent activation of the kinase in vivo has been questioned because the dissociation constant of Sestrin2 for leucine is well below circulating and intramuscular levels of the amino acid.

Validation of a commercially available anti-REDD1 antibody using RNA interference and REDD1-/- mouse embryonic fibroblasts.

REDD1 is a transcriptional target gene of p53 and HIF-1, and an inhibitor of mTOR (mechanistic target of rapamycin) complex 1 (mTORC1)-signaling through PP2A-dependent interaction, making it an important convergence point of both tumor suppression and cell growth pathways. In accordance with this positioning, REDD1 levels are transcriptionally upregulated in response to a variety of cellular stress factors such as nutrient deprivation, hypoxia and DNA damage. In the absence of such conditions, and in particular where growth factor signaling is activated, REDD1 expression is typically negligible; therefore, it is necessary to induce REDD1 prior to experimentation or detection in model systems.

Disruption of genes encoding eIF4E binding proteins-1 and -2 does not alter basal or sepsis-induced changes in skeletal muscle protein synthesis in male or female mice.

Sepsis decreases skeletal muscle protein synthesis in part by impairing mTOR activity and the subsequent phosphorylation of 4E-BP1 and S6K1 thereby controlling translation initiation; however, the relative importance of changes in these two downstream substrates is unknown. The role of 4E-BP1 (and -BP2) in regulating muscle protein synthesis was assessed in wild-type (WT) and 4E-BP1/BP2 double knockout (DKO) male mice under basal conditions and in response to sepsis. At 12 months of age, body weight, lean body mass and energy expenditure did not differ between WT and DKO mice.

Effects of oxidized corn oil and a synthetic antioxidant blend on performance, oxidative status of tissues, and fresh meat quality in finishing barrows.

The objective was to evaluate the effect of feeding oxidized corn oil with or without a dietary antioxidant (AOX) on performance, tissue oxidative status, and meat quality in barrows. One hundred sixty barrows were arranged in a 2 × 2 factorial of treatments in a complete randomized block design with 8 pens per treatment and 5 pigs per pen. Diets contained 5.

Continuous infusion of 20-hydroxyecdysone increased mass of triceps brachii in C57BL/6 mice.

Phytoecdysteroids have been attributed with numerous pharmacological properties in animals, including increasing muscle mass, and 20-hydroxyecdysone (20E) is one of the most abundant phytoecdysteroids produced by plants. In this study, the physiological and gene expression effects of 20E were analyzed in C57BL/6 mice given a continuous infusion of saline or 20E (5 mg/kg/day) for 5 or 15 days using subcutaneously implanted Alzet® osmotic pumps. The masses of the total body, muscle groups and organs were determined.

Varying the temperature of the liquid used for high-pressure processing of prerigor pork: effects on fresh pork quality, myofibrillar protein solubility, and frankfurter textural properties.

Unlabelled: The objective was to evaluate high-pressure processing (HPP) with varying liquid (water) temperatures on pork quality and textural properties of frankfurters. HPP pressurization liquid temperatures were 15.5 °C (HPP Low) and 29.

Toll-like receptor activation suppresses ER stress factor CHOP and translation inhibition through activation of eIF2B.

Activation of Toll-like receptors (TLRs) induces the endoplasmic reticulum (ER) unfolded protein response (UPR) to accommodate essential protein translation. However, despite increased levels of phosphorylated eIF2α (p-eIF2α), a TLR-TRIF-dependent pathway assures that the cells avoid CHOP induction, apoptosis and translational suppression of critical proteins. As p-eIF2α decreases the functional interaction of eIF2 with eIF2B, a guanine nucleotide exchange factor (GEF), we explored the hypothesis that TLR-TRIF signalling activates eIF2B GEF activity to counteract the effects of p-eIF2α.

Muscle gene expression associated with increased marbling in beef cattle.

The objective of this study was to identify specific bovine genes expressed within skeletal muscle that are associated with intramuscular fat deposition. Twenty-eight Angus-Simmental cross steers and heifers were harvested at the University of Illinois Meat Science Laboratory. Four pairs of animals were identified based on similar adjusted backfat thickness but differing amounts of intramuscular fat within each pair.

Effects of increasing lysine on carcass composition and cutting yields of immunologically castrated male pigs.

The objective of this experiment was to determine if increasing lysine in the diets of immunologically castrated (IC) male pigs would increase percentage fat free lean and carcass cutting yields when compared with physical castrates. The anti-gonadotropin-releasing factor (GnRF) immunological product (Improvest, Pfizer Animal Health) is used worldwide to immunologically castrate entire male pigs to control boar taint and take advantage of the inherent ability of the entire male to deposit more muscle, less fat, and grow more efficiently than physically castrated males. The immunization process essentially allows the pig to grow as an entire male pig for most of its life and then removes any boar odor (boar taint) before slaughter.

Comparison of varying doses and durations of ractopamine hydrochloride on late-finishing pig carcass characteristics and meat quality.

The objective was to investigate the effect of various doses and durations of ractopamine hydrochloride (RAC) on pig HCW, cutting yields, and meat quality. Late-finishing pigs (approximately 93 kg) were allotted to 12 treatments 35 d before slaughter. Treatments consisted of negative control (NEG; 13.

Multi-modal proteomic analysis of retinal protein expression alterations in a rat model of diabetic retinopathy.

Background: As a leading cause of adult blindness, diabetic retinopathy is a prevalent and profound complication of diabetes. We have previously reported duration-dependent changes in retinal vascular permeability, apoptosis, and mRNA expression with diabetes in a rat model system. The aim of this study was to identify retinal proteomic alterations associated with functional dysregulation of the diabetic retina to better understand diabetic retinopathy pathogenesis and that could be used as surrogate endpoints in preclinical drug testing studies.

The effects of high pressure processing on pork quality, palatability, and further processed products.

The objective was to evaluate high pressure processing (HPP) on postmortem metabolism and pork quality. Six pigs were randomly selected immediately after slaughter. After splitting, one side was randomly designated for HPP of 215 MPa for 15 s with water temperature at 33 °C and the other side (non-pressure treated) served as the control.

The myostatin null mutation and clenbuterol administration elicit additive effects in mice.

In mice, the myostatin (Mstn) null mutation and treatment with clenbuterol both increase muscle growth and decrease fat mass. Our objective was to determine whether mechanistic overlap exists by administering clenbuterol to Mstn null mice. Male Mstn null and wild-type mice of similar genetic backgrounds received either 0 (control) or 20 p.

Sodium citrate as a replacement for sodium chloride in a brine solution when evaluated in cows of different backfat thickness.

The objective of this study was to evaluate seven muscles from cow forequarters, which were selected based on backfat thickness; an indicator of supplemental feed before slaughter: Moderate cover (Moderate ⩾ 0.76cm) and Thin cover (Thin ⩽ 0.51cm).

Rapid turnover of the mTOR complex 1 (mTORC1) repressor REDD1 and activation of mTORC1 signaling following inhibition of protein synthesis.

mTORC1 is a complex of proteins that includes the mammalian target of rapamycin (mTOR) and several regulatory proteins. It is activated by a variety of hormones (e.g.