Article
Multidisciplinary Sciences
Qiwei Jiang, Xiaomei Zhang, Xiaoming Dai, Shiyao Han, Xueji Wu, Lei Wang, Wenyi Wei, Ning Zhang, Wei Xie, Jianping Guo
Summary: The study demonstrates that S6K1 can directly phosphorylate PDK1, inhibiting the activity of AKT kinase and its role in tumorigenesis. This feedback regulation of AKT signaling through S6K1-mediated PDK1 phosphorylation provides insight into the regulation of the AKT pathway and potential strategies for combating mutant PDK1-driven cancers.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Maria J. Conde-Dusman, Partha N. Dey, Oscar Elia-Zudaire, Luis G. Rabaneda, Carmen Garcia-Lira, Teddy Grand, Victor Briz, Eric R. Velasco, Raul Andero, Sergio Ninerola, Angel Barco, Pierre Paoletti, John F. Wesseling, Fabrizio Gardoni, Steven J. Tavalin, Isabel Perez-Otano
Summary: The study reveals that synaptic protein synthesis can be regulated by controlling the complex formation of GIT1/mTOR and the binding of NMDA receptors containing GluN3A subunits. Removing GluN3A enhances mTOR-dependent protein synthesis, facilitating memory consolidation. The findings provide insight into synaptic translational control and suggest a potential target for cognitive enhancement.
Article
Cell Biology
Shuang Cai, Qianhong Ye, Xiangzhou Zeng, Guangxin Yang, Changchuan Ye, Meixia Chen, Haitao Yu, Yuming Wang, Gang Wang, Shuo Huang, Shuang Quan, Xiangfang Zeng, Shiyan Qiao
Summary: The research indicates that methionine deficiency during early pregnancy significantly reduces the number of embryo implantation sites, CBS expression, and products of the transsulfuration pathway, which can be reversed by maternal methionine supplementation. Additionally, CBS influences signaling pathways related to cell proliferation and DNA synthesis, and there may be a correlation between CBS and MAT2A, suggesting a potential involvement of MAT2A in these processes.
CELL PROLIFERATION
(2021)
Article
Cell Biology
Wanchun Yang, Dejiang Pang, Mina Chen, Chongyangzi Du, Lanlan Jia, Luoling Wang, Yunling He, Wanxiang Jiang, Liping Luo, Zongyan Yu, Mengqian Mao, Qiuyun Yuan, Ping Tang, Xiaoqiang Xia, Yiyuan Cui, Bo Jing, Alexander Platero, Yanhui Liu, Yuquan Wei, Paul F. Worley, Bo Xiao
Summary: Rheb regulates mitochondrial energy production through PDH activation, maintaining neuronal activity balance. Cell-specific Rheb genetic models highlight the importance of the Rheb-PDH axis in modulating PDH phosphorylation/activity, acetyl-CoA, and ATP levels.
DEVELOPMENTAL CELL
(2021)
Article
Chemistry, Multidisciplinary
Su-Ling Huang, Wei Xie, Yang-Liang Ye, Jia Liu, Hui Qu, Yu Shen, Ti-Fei Xu, Zhuo-Hui Zhao, Yu Shi, Jian-Hua Shen, Ying Leng
Summary: Coronarin A, a natural compound isolated from rhizomes of Hedychium gardnerianum, has shown potential in controlling hyperglycemia in type 2 diabetes mellitus (T2DM) by simultaneously stimulating glycogen synthesis and suppressing gluconeogenesis. It activates the PI3K/Akt/GSK3 beta and ERK/Wnt/β-catenin signaling pathways and enhances IRS1 activity. In an animal study involving T2DM mice, chronic administration of coronarin A reduced blood glucose levels and improved glucose tolerance by inhibiting hepatic mTOR/S6K1 signaling and activating IRS1.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Multidisciplinary Sciences
Sofia Cabezudo, Maria Sanz-Flores, Alvaro Caballero, Inmaculada Tasset, Elena Rebollo, Antonio Diaz, Anna M. Aragay, Ana Maria Cuervo, Federico Mayor Jr, Catalina Ribas
Summary: The G alpha q subunit plays a crucial role in modulating mTORC1 and autophagy, affecting basal autophagy levels and mTORC1 activation status. Its interaction with p62 contributes to the formation of mTOR-p62-Raptor complex, regulating autophagy in response to nutrient status fluctuations.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Rui Liu, Lin-Wen Zeng, Rong Gong, Fanen Yuan, Hong-Bing Shu, Shu Li
Summary: mTORC1 signaling inhibits GLDC acetylation at K514 by inducing SIRT3 transcription, which impairs its enzymatic activity and affects glycine metabolism and tumorigenesis.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Organic
Youzhi Li, Franck Touret, Xavier de Lamballerie, Michel Nguyen, Marion Laurent, Francoise Benoit-Vical, Anne Robert, Yan Liu, Bernard Meunier
Summary: This study focuses on the availability of small and effective drugs for controlling viral infections in humans in the field of medicinal chemistry. A series of hybrid molecules combining emodin and other structural moieties were synthesized and evaluated for their biological activities. It was found that one of the compounds exhibited high potency against SARS-CoV-2. However, these compounds were not effective competitors to currently used antimalarial drugs.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Raef Shams, Yoshihiro Ito, Hideyuki Miyatake
Summary: This study reports the development of a potential peptide compound, P1_WT, that can inhibit mTORC1 activity by intercepting its interaction with RHEB. P1_WT binds to RHEB and inhibits its interaction with mTOR, resulting in the inhibition of mTORC1 activity.
Article
Cell Biology
Xinxin Chi, Wei Jin, Xue Bai, Xiaohong Zhao, Jing Shao, Jiaqi Li, Qinli Sun, Bing Su, Xiaohu Wang, Xuexian O. Yang, Chen Dong
Summary: The study found that RORα is highly expressed in active UC patients, especially in those non-responsive to anti-TNF treatment. RORα plays a crucial role in promoting IBD development in CD4(+) T cells by regulating T cell infiltration, inhibiting T cell apoptosis, and promoting mTORC1 activation. This indicates that the RORα-mTORC1 axis may be a potential therapeutic target for human patients with IBD.
Article
Multidisciplinary Sciences
Yilei Zhang, Robert Swanda, Litong Nie, Xiaoguang Liu, Chao Wang, Hyemin Lee, Guang Lei, Chao Mao, Pranavi Koppula, Weijie Cheng, Jie Zhang, Zhenna Xiao, Li Zhuang, Bingliang Fang, Junjie Chen, Shu-Bing Qian, Boyi Gan
Summary: Cystine uptake promotes GPX4 synthesis by activating mTORC1, sensitizing cancer cells to ferroptosis. Inhibiting mTORC1 decreases GPX4 protein levels and enhances the effectiveness of ferroptosis inducers in cancer treatment.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Zhengnian Li, Ryosuke Ishida, Yan Liu, Jinhua Wang, Yina Li, Yang Gao, Jie Jiang, Jianwei Che, Jason M. Sheltzer, Matthew B. Robers, Tinghu Zhang, Kenneth D. Westover, Behnam Nabet, Nathanael S. Gray
Summary: This study describes a medicinal chemistry campaign to identify a CDK11 inhibitor. Through structure-guided medicinal chemistry modifications, a CDK11 probe ZNL-05-044 with improved selectivity was identified, which can arrest cell cycle and impact CDK11-dependent gene splicing in cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Cell Biology
Li Xia, Tiejian Nie, Fangfang Lu, Lu Huang, Xiaolong Shi, Dongni Ren, Jianjun Lu, Xiaobin Li, Tuo Xu, Bozhou Cui, Qing Wang, Guodong Gao, Qian Yang
Summary: This study discovered a transcriptional regulatory mechanism of MTORC1 involving MEF2A and MEF2D. MEF2A and MEF2D control the cyto-lysosome shutting of MTORC1 by regulating the transcription of FNIP1 and FNIP2, and tyrosine phosphorylation of MEF2D by SRC/c-Src enhances its transcriptional activity and is necessary for MTORC1 activation. The protein and tyrosine phosphorylation levels of MEF2D are elevated in pancreatic cancer and positively correlated with MTORC1 activity.
Article
Biochemistry & Molecular Biology
Zhen-hua Liu, Wen-wen Xie, Geng-xiu Zan, Chun-qi Gao, Hui-chao Yan, Jia-yi Zhou, Xiu-qi Wang
Summary: The study demonstrated that lauric acid can alleviate deoxynivalenol-induced intestinal epithelial damage and promote intestinal stem cell regeneration. Lauric acid improved the morphology and barrier function of the jejunum damaged by deoxynivalenol, and promoted the differentiation of intestinal cells.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Cell Biology
Shasha Yin, Liu Liu, Lauren E. Ball, Yalong Wang, Mark T. Bedford, Stephen A. Duncan, Haizhen Wang, Wenjian Gan
Summary: This study identifies protein arginine methyltransferase 1 (PRMT1) as a critical regulator of the GATOR2 complex, which activates the mTORC1 pathway for tumor growth. Inhibition of the CDK5-PRMT1-WDR24 axis suppresses HCC cell proliferation and tumor growth. High PRMT1 protein expression is associated with elevated mTORC1 signaling in patients with HCC.
Article
Physiology
Marcus Moberg, William Apro, Oscar Horwath, Gerrit van Hall, Sarah Joan Blackwood, Abram Katz
Summary: Acute severe hypoxia inhibits signaling pathways involved in muscle growth regulation, including mTORC1 and JNK signaling. These effects do not appear to be mediated by changes in the degree of metabolic stress in the muscle.
Article
Endocrinology & Metabolism
Sarah J. Blackwood, Oscar Horwath, Marcus Moberg, Marjan Ponten, William Apro, Maria M. Ekblom, Filip J. Larsen, Abram Katz
Summary: Muscle fiber composition differences are associated with alterations in peripheral insulin action and secretion, which can be used to predict insulin resistance and glucose-stimulated insulin secretion.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Cell Biology
Fabian Nordstrom, Rasmus Liegnell, William Apro, Sarah J. Blackwood, Abram Katz, Marcus Moberg
Summary: GPR81 is a protein receptor that binds to L-lactate and inhibits cAMP-PKA-CREB signaling pathway. This study investigates the expression of GPR81 and related signaling in human skeletal muscle under conditions of elevated lactate levels.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Sport Sciences
Anna Katharina Dunst, Clemens Hesse, Olaf Ueberschaer, Hans-Christer Holmberg
Summary: During maximal cycling sprints, efficiency is determined by muscle fiber composition and cadence-dependent power output. This study introduces the concept of optimal efficiency, which eliminates the impact of cadence, and compares it to actual data. The time course of maximal power output is proposed as an indicator of changes in optimal efficiency.
Article
Physiology
Mikael Flockhart, Dominik Tischer, Lina C. Nilsson, Sarah J. Blackwood, Bjoern Ekblom, Abram Katz, William Apro, Filip J. Larsen
Summary: The study aimed to investigate the effects of different types of exercise on glucose tolerance, assess the potential differences between two exercise paradigms in relation to changes in mitochondrial function, and determine if endurance athletes differ from nonendurance-trained controls in their metabolic responses. The results showed that prolonged exercise reduces glucose tolerance and increases insulin resistance in endurance athletes the following day. These findings are associated with an increased lipid load, high lipid oxidation capacity, and increased fat oxidation.
Article
Endocrinology & Metabolism
Sarah J. Blackwood, Oscar Horwath, Marcus Moberg, Marjan Ponten, William Apro, Maria M. Ekblom, Filip J. Larsen, Abram Katz
Summary: This study examined the effect of muscle fiber composition on metabolic responses to a 3-day fast. The results showed that the group with a higher proportion of type I muscle fibers had a greater loss of insulin sensitivity and a higher capacity to oxidize lipids after starvation.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Oscar Horwath, Fabian Nordstrom, Ferdinand von Walden, William Apro, Marcus Moberg
Summary: Cumulative evidence supports the hypothesis that hypoxia acts as a regulator of muscle mass. This study examined the effect of hypoxia on signaling pathways and gene expression in human skeletal muscle after resistance exercise. The results showed that hypoxia attenuated ribosome signaling but did not affect satellite cell pool expansion and myogenic gene expression.
Article
Physiology
Mats Lilja, Marcus Moberg, William Apro, Luis Manuel Martinez-Aranda, Hakan Rundqvist, Billy Langlet, Thomas Gustafsson, Tommy R. Lundberg
Summary: We investigated the effects of ibuprofen and low-dose aspirin on muscle hypertrophy in young adults undergoing resistance training. The study found that there were no significant differences in molecular markers, muscle fiber size, ribosome biogenesis, satellite cell content, myonuclear accretion, and angiogenesis between the two groups. However, the mRNA levels of atrogin-1 and MuRF-1 were more downregulated in the low-dose aspirin group after acute exercise. These findings suggest that the previously reported deleterious effects of high doses of ibuprofen on muscle hypertrophy may not be explained by these established hypertrophy regulators.
JOURNAL OF APPLIED PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
M. Flockhart, L. C. Nilsson, E. N. Tillqvist, F. Vinge, F. Millbert, J. Lannerstrom, P. H. Nilsson, D. Samyn, W. Apro, M. L. Sundqvist, F. J. Larsen
Summary: Oxidative stress plays a vital role in the adaptive responses to physical training. Glucosinolates from cruciferous vegetables can be converted into antioxidative compounds that activate crucial antioxidant defence pathways and improve mitochondrial function and protein integrity. In this study, combining glucosinolate-rich broccoli sprouts with exercise significantly reduced protein oxidation levels, improved physical performance, and mitigated nocturnal hypoglycaemia.
Article
Sport Sciences
Anna Katharina Dunst, Clemens Hesse, Olaf Ueberschaer, Hans-Christer Holmberg
Summary: This study compares two different methods for calculating maximal force-velocity (F/v) profiles and finds that the first method leads to higher extrapolated isometric force and steeper slope. Additionally, the study shows excellent model consistency for F/v profiles derived from sprints with different gear ratios.
Article
Sport Sciences
Andreas Almqvist, Barbara Pellegrini, Nina Lintzen, Nazanin Emami, H-C Holmberg, Roland Larsson
Summary: This article specifically describes the research progress and influencing factors of ski-snow friction. The stiffness, shape, and material composition of the ski base play important roles in ski-snow friction. Understanding the interactions between these factors and combining information such as temperature and humidity can help design strategies to reduce friction.
FRONTIERS IN SPORTS AND ACTIVE LIVING
(2022)