Article
Environmental Sciences
Tingting Ku, Mengmeng Zhou, Yanwen Hou, Yuanyuan Xie, Guangke Li, Nan Sang
Summary: The study found that low doses of tebuconazole mainly accumulated in the liver of mice, causing histopathological damage. Tebuconazole significantly dysregulated metabolizing enzymes, efflux transporters, and fatty acid metabolism-related genes in the liver, leading to liver hypertrophy and steatosis. Furthermore, excessive induction of ROS and oxidative stress partly accounted for the metabolic abnormalities mediated by tebuconazole.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Cell Biology
Alba Capelo-Diz, Sofia Lachiondo-Ortega, David Fernandez-Ramos, Jorge Canas-Martin, Naroa Goikoetxea-Usandizaga, Marina Serrano-Macia, Maria J. Gonzalez-Rellan, Laura Mosca, Joan Blazquez-Vicens, Alberto Tinahones-Ruano, Marcos F. Fondevila, Mason Buyan, Teresa C. Delgado, Virginia Gutierrez de Juan, Paula Ayuso-Garcia, Alejandro Sanchez-Rueda, Sergio Velasco-Aviles, Hector Fernandez-Susavila, Cristina Riobello-Suarez, Bartlomiej Dziechciarz, Cristina Montiel-Duarte, Fernando Lopitz-Otsoa, Maider Bizkarguenaga, Jon Bilbao-Garcia, Ganeko Bernardo-Seisdedos, Ana Senra, Mario Soriano-Navarro, Oscar Millet, Angel Diaz-Lagares, Ana B. Crujeiras, Aida Bao-Caamano, Diana Cabrera, Sebastiaan van Liempd, Miguel Tamayo-Caro, Luigi Borzacchiello, Beatriz Gomez-Santos, Xabier Buque, Diego Saenz de Urturi, Francisco Gonzalez-Romero, Jorge Simon, Ruben Rodriguez-Agudo, Asier Ruiz, Carlos Matute, Daniel Beiroa, Juan M. Falcon-Perez, Patricia Aspichueta, Juan Rodriguez-Cuesta, Marina Porcelli, Maria A. Pajares, Cristina Ameneiro, Miguel Fidalgo, Ana M. Aransay, Tomas Lama-Diaz, Miguel G. Blanco, Miguel Lopez, Ricardo Villa-Bellosta, Timo D. Mueller, Ruben Nogueiras, Ashwin Woodhoo, Maria Luz Martinez-Chantar, Marta Varela-Rey
Summary: This study reveals that hepatic S-adenosylmethionine (SAMe) acts as a metabolic sensor of nutrition and fine-tunes the fasting response by regulating various cellular processes in mice. It shows that SAMe modulates PEMT activity, ER-mitochondria contacts, lipid oxidation, ATP production in the liver, and FGF21-mediated lipolysis and thermogenesis in adipose tissues. Additionally, the study highlights the role of glucagon-induced SAMe synthesis in preventing excessive lipid oxidation and mitochondrial ATP synthesis, thereby protecting against ER stress and liver injury.
Article
Environmental Sciences
Daqian Yang, Xiaoting Zhang, Lei Yue, Hailong Hu, Xiangjuan Wei, Qian Guo, Boya Zhang, Xingpei Fan, Yuan Xin, Yuri Oh, Ning Gu
Summary: Chronic exposure to TMX can induce dyslipidemia and NAFLD in mice, accompanied by increased oxidative stress and disruption of liver structure. The upregulation of PPAR gamma, fatty acid synthase, and NNMT expression, along with downregulation of PPAR alpha and GNMT expression, suggest a potential mechanism involving NNMT-mediated methionine metabolism and methyl donor balance in TMX-induced NAFLD. Inhibition of NNMT may be a novel strategy to prevent NAFLD progression caused by TMX.
Article
Gastroenterology & Hepatology
Long Xu, Yang Yang, Yankai Wen, Jong-Min Jeong, Christoph Emontzpohl, Constance L. Atkins, Zhaoli Sun, Kyle L. Poulsen, David R. Hall, J. Steve Bynon, Bin Gao, William M. Lee, Jody Rule, Elizabeth A. Jacobsen, Hua Wang, Cynthia Ju
Summary: This study reveals the recruitment of eosinophils into the liver and their protective function during acetaminophen-induced acute liver injury. The data demonstrate that IL-33-activated eosinophils trigger macrophages to release high amounts of CCL24, which promotes hepatic eosinophil recruitment. Our findings suggest that eosinophils could be an effective cell-based therapy for the treatment of acetaminophen-induced acute liver injury.
JOURNAL OF HEPATOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Xiaoyangzi Li, Ruyang Lao, Jiawei Lei, Yuting Chen, Qi Zhou, Ting Wang, Yingpeng Tong
Summary: The liver plays a crucial role in the body's metabolism, synthesis, and detoxification processes, but it is susceptible to damage from various factors. Drug-induced liver injury can be particularly problematic for patients, emphasizing the need for research on new treatment options.
Article
Pharmacology & Pharmacy
Yi-Ming Chang, Po-Chun Chen, Chien-Peng Hsu, Peng-Fang Ma, Huey-Ling Chen, Shu-Hao Hsu
Summary: The microRNAs miR-192 and miR-194 are abundant in the liver and serve as serum biomarkers of liver injury. This study showed that genetic depletion of miR-194 promoted liver regeneration and protected against APAP-induced injury.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Food Science & Technology
Yuhui Yang, Manman Lu, Yuncong Xu, Jing Qian, Guowei Le, Yanli Xie
Summary: This study investigated the effects of different dietary methionine levels on hepatic lipid accumulation in mice and found that high dietary methionine intake can promote liver lipid accumulation, inhibit lipid and glycolysis metabolism, and increase oxidative stress and inflammation in the liver. Methionine restriction can reverse these adverse effects.
FOOD RESEARCH INTERNATIONAL
(2022)
Article
Biochemistry & Molecular Biology
Yi Zhang, Mirandia Szramowski, Shuhan Sun, Gregory C. Henderson
Summary: This study investigates the combined effect of albumin deficiency and acute exercise on hepatic lipid droplets (LDs). The results show that mice with albumin deficiency exhibit a significant reduction in the size and content of hepatic LDs after acute exercise. These findings suggest that modulating albumin's functions combined with exercise could be a potential strategy to reduce ectopic lipid deposition in the liver.
LIPIDS IN HEALTH AND DISEASE
(2023)
Article
Pharmacology & Pharmacy
Jing Sun, Zhixuan Hong, Shuai Shao, Lu Li, Bei Yang, Yongyong Hou, Huihui Wang, Yuanyuan Xu, Qiang Zhang, Jingbo Pi, Jingqi Fu
Summary: Hepatic Nrf2 plays a critical role in the development of ALD, particularly influencing morbidity and liver injury.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Article
Endocrinology & Metabolism
Vanessa Byles, Yann Cormerais, Krystle Kalafut, Victor Barrera, James E. Hughes Hallett, Shannan Ho Sui, John M. Asara, Christopher M. Adams, Gerta Hoxhaj, Issam Ben-Sahra, Brendan D. Manning
Summary: The study demonstrates that ATF4 is stimulated by mTORC1 signaling in the liver in response to insulin during feeding, leading to changes in hepatocyte gene expression and metabolism. While insulin stimulates de novo purine and pyrimidine synthesis through mTORC1 signaling in primary hepatocytes, this regulation is independent of ATF4.
MOLECULAR METABOLISM
(2021)
Article
Pharmacology & Pharmacy
Xuemin Zhang, Xijuan Ren, Weiqiang Sun, Nathan Griffin, Li Wang, Hui Liu
Summary: This study investigated the mechanisms of PFOA toxicity in the liver of exposed male rats. The results showed that exposure to PFOA induced liver damage, altered metabolism, and affected the expression of AMPK/mTOR pathway related genes and proteins.
Article
Biology
Parker S. Woods, Lucas M. Kimmig, Kaitlyn A. Sun, Angelo Y. Meliton, Obada R. Shamaa, Yufeng Tian, Renguel Cetin-Atalay, Willard W. Sharp, Robert B. Hamanaka, Goekhan M. Mutlu
Summary: Cellular metabolism plays a crucial role in regulating macrophage function. Changes in local oxygen concentration, such as those seen in conditions like acute respiratory distress syndrome (ARDS), can impact the metabolism and function of tissue-resident alveolar macrophages (TR-AMs), leading to their progressive loss which correlates with disease severity and mortality. Targeting cellular metabolism, particularly under hypoxic conditions, may hold therapeutic potential in improving outcomes in diseases characterized by acute inflammation.
Article
Multidisciplinary Sciences
Oscar Aubi, Karina S. Prestegard, Kunwar Jung-KC, Tie-Jun Sten Shi, Ming Ying, Ann Kari Grindheim, Tanja Scherer, Arve Ulvik, Adrian McCann, Endy Spriet, Beat Thony, Aurora Martinez
Summary: Phenylketonuria (PKU) is caused by autosomal recessive variants in phenylalanine hydroxylase (PAH) and can lead to neurotoxicity. Here the authors describe a mouse model of PKU based on a mutation in phenylalanine hydroxylase (R261Q) which replicates traits of this disease and shows a proteostasis defect and oxidative stress, implying a gain-of-function contribution to the disease phenotype.
NATURE COMMUNICATIONS
(2021)
Article
Environmental Sciences
Hu Zhang, Xiaofang Wang, Mingrong Qian, Yuanxiang Jin
Summary: The study found that exposure to ATZ caused hepatic metabolism disorder in zebrafish, resulting in decreased triglyceride levels and increased pyruvate and total cholesterol levels in the liver. Metabolomic analysis showed that ATZ affected the arginine, proline, and glutathione metabolic pathways in zebrafish.
Article
Multidisciplinary Sciences
Cathelijne Heymans, Marcel den Dulk, Kaatje Lenaerts, Lara R. Heij, Ilse H. de Lange, Mhamed Hadfoune, Chantal van Heugten, Boris W. Kramer, Alan H. Jobe, Masatoshi Saito, Matthew W. Kemp, Tim G. A. M. Wolfs, Wim G. van Gemert
Summary: Research indicates that intra-amniotic LPS exposure causes time-dependent changes in fetal liver and enterohepatic circulation in lambs, including hepatic inflammation and increased bile acid levels, but EHC alterations normalize over time. These changes may have postnatal consequences, highlighting the potential importance of the duration of intra-amniotic LPS exposure.
SCIENTIFIC REPORTS
(2021)
Article
Pharmacology & Pharmacy
Juan M. Gonzalez-Morena, Francisco J. Sanchez-Gomez, Yolanda Vida, Ezequiel Perez-Inestrosa, Maria Salas, Maria I. Montanez, Alessandra Altomare, Giancarlo Aldini, Maria A. Pajares, Dolores Perez-Sala
Summary: Allergic reactions to antibiotics, especially β-lactam antibiotics, are a major concern in the clinic. In this study, we identified alpha-enolase as a target for haptenation by amoxicillin, and investigated the interactions between amoxicillin haptenation and acetylation of alpha-enolase. We also identified the specific target sequence on alpha-enolase for amoxicillin binding. These findings provide a basis for the development of novel diagnostic tools and approaches for studying amoxicillin-induced allergic reactions.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Vasiliki Lalioti, Silvia Gonzalez-Sanz, Irene Lois-Bermejo, Patricia Gonzalez-Jimenez, Alvaro Viedma-Poyatos, Andrea Merino, Maria A. Pajares, Dolores Perez-Sala
Summary: The study explores the interaction between SARS-CoV-2 Spike protein and various cell types. The results reveal that Spike protein primarily colocalizes with ACE2 on the cell surface, and to a lesser extent with lipid raft markers. Additionally, vimentin is unevenly distributed on the cell surface. Interestingly, vimentin shows moderate colocalization with ACE2 or Spike, but is enriched in ciliated structures. These findings suggest that ciliated structures may serve as platforms for SARS-CoV-2 docking.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Irene Lois-Bermejo, Patricia Gonzalez-Jimenez, Sofia Duarte, Maria A. Pajares, Dolores Perez-Sala
Summary: The tail segments of vimentin protein show differential accessibility at distinct subcellular locations. The 411-423 segment is accessible in all areas, while the 419-438 segment is less recognized in perinuclear regions and lipoxidative stress-induced bundles. These different arrangements may be interconverted by posttranslational modifications.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Alvaro Viedma-Poyatos, Patricia Gonzalez-Jimenez, Maria A. Pajares, Dolores Perez-Sala
Summary: Alexander disease, caused by mutations in the intermediate filament protein GFAP, leads to astrocyte dysfunction and neurodegeneration. The mutated GFAP is more susceptible to oxidation and lipoxidation, which contribute to the disease progression.
Article
Nutrition & Dietetics
Marina Redruello-Requejo, Maria de Lourdes Samaniego-Vaesken, Ana M. Puga, Ana Montero-Bravo, Mar Ruperto, Paula Rodriguez-Alonso, Teresa Partearroyo, Gregorio Varela-Moreiras
Summary: The dietary intake of omega-3 polyunsaturated fatty acids among the Spanish population is inadequate, especially in children, adolescents, and younger women. The intake of omega-6 polyunsaturated fatty acids is relatively acceptable, but the ratio of omega-6 to omega-3 is high. Meat and meat products are the main source of essential fatty acids, while fish and shellfish are the only sources of EPA and DHA. The combined degree of inadequacy for omega-3 PUFA, folic acid, vitamin B-12, and choline is 21.3% in the ANIBES population.
Review
Biochemistry & Molecular Biology
Dolores Perez-Sala, Maria A. Pajares
Summary: The metabolism and intercellular transfer of glutathione play a significant role in cellular defense against oxidative stress. Astrocytes are believed to produce glutathione for neurons, but the energy expenditure and the ability of neurons to import and synthesize glutathione precursors raise questions. Astrocytic glutathione release may affect the redox status of the extracellular environment and stimulate neuronal import, contributing to a more reduced environment. Recent evidence challenges the assumption of astrocytes as the primary suppliers of neuronal glutathione precursors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Alba Capelo-Diz, Sofia Lachiondo-Ortega, David Fernandez-Ramos, Jorge Canas-Martin, Naroa Goikoetxea-Usandizaga, Marina Serrano-Macia, Maria J. Gonzalez-Rellan, Laura Mosca, Joan Blazquez-Vicens, Alberto Tinahones-Ruano, Marcos F. Fondevila, Mason Buyan, Teresa C. Delgado, Virginia Gutierrez de Juan, Paula Ayuso-Garcia, Alejandro Sanchez-Rueda, Sergio Velasco-Aviles, Hector Fernandez-Susavila, Cristina Riobello-Suarez, Bartlomiej Dziechciarz, Cristina Montiel-Duarte, Fernando Lopitz-Otsoa, Maider Bizkarguenaga, Jon Bilbao-Garcia, Ganeko Bernardo-Seisdedos, Ana Senra, Mario Soriano-Navarro, Oscar Millet, Angel Diaz-Lagares, Ana B. Crujeiras, Aida Bao-Caamano, Diana Cabrera, Sebastiaan van Liempd, Miguel Tamayo-Caro, Luigi Borzacchiello, Beatriz Gomez-Santos, Xabier Buque, Diego Saenz de Urturi, Francisco Gonzalez-Romero, Jorge Simon, Ruben Rodriguez-Agudo, Asier Ruiz, Carlos Matute, Daniel Beiroa, Juan M. Falcon-Perez, Patricia Aspichueta, Juan Rodriguez-Cuesta, Marina Porcelli, Maria A. Pajares, Cristina Ameneiro, Miguel Fidalgo, Ana M. Aransay, Tomas Lama-Diaz, Miguel G. Blanco, Miguel Lopez, Ricardo Villa-Bellosta, Timo D. Mueller, Ruben Nogueiras, Ashwin Woodhoo, Maria Luz Martinez-Chantar, Marta Varela-Rey
Summary: This study reveals that hepatic S-adenosylmethionine (SAMe) acts as a metabolic sensor of nutrition and fine-tunes the fasting response by regulating various cellular processes in mice. It shows that SAMe modulates PEMT activity, ER-mitochondria contacts, lipid oxidation, ATP production in the liver, and FGF21-mediated lipolysis and thermogenesis in adipose tissues. Additionally, the study highlights the role of glucagon-induced SAMe synthesis in preventing excessive lipid oxidation and mitochondrial ATP synthesis, thereby protecting against ER stress and liver injury.
Editorial Material
Biochemistry & Molecular Biology
Maria angeles Pajares
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Patricia Gonzalez-Jimenez, Sofia Duarte, Alma E. Martinez, Elena Navarro-Carrasco, Vasiliki Lalioti, Maria A. Pajares, Dolores Perez-Sala
Summary: This article investigates the role of the cysteine residue C328 in vimentin protein in responding to various chemical agents, and reveals that C328 plays a crucial role in the rearrangement and cellular response of vimentin.
Article
Biochemistry & Molecular Biology
Diego Moneo-Corcuera, Alvaro Viedma-Poyatos, Konstantinos Stamatakis, Dolores Perez-Sala
Summary: The behavior of desmin, a muscle-specific intermediate filament protein, is affected by oxidants and cysteine-reactive agents. Oxidative stress and lipoxidation disrupt the organization of desmin in muscle cells, and this effect is partially reduced in mutant forms.
Review
Cell Biology
Maria A. Pajares, Elena Hernandez-Gerez, Milos Pekny, Dolores Perez-Sala
Summary: Alexander disease is a rare neurodegenerative disorder caused by mutations in the glial fibrillary acidic protein, leading to characteristic aggregates in astrocytes. The impact of mutations on protein expression, posttranslational modifications, and protein-protein interactions of the mutant protein may impair astrocyte function and affect neurons. Experimental models are being developed to study the disease and potential therapeutic strategies.
NEURAL REGENERATION RESEARCH
(2023)
Article
Clinical Neurology
Isaac Canals, Andrea Comella-Bolla, Efrain Cepeda-Prado, Natalia Avaliani, James A. Crowe, Leal Oburoglu, Andreas Bruzelius, Naomi King, Maria A. Pajares, Dolores Perez-Sala, Andreas Heuer, Daniella Rylander Ottosson, Jordi Soriano, Henrik Ahlenius
Summary: Canals et al. report a new disease model of Frontotemporal Dementia generated with genome editing of the CHMP2B gene in human embryonic stem cells, differentiated to induced neurons and astrocytes, and generating neuron-astrocyte co-cultures to identify impaired astrocytic glutamate homeostasis and evident alterations in neuronal network connectivity and synchronization.
BRAIN COMMUNICATIONS
(2023)