Review
Biochemistry & Molecular Biology
Stepanka Benakova, Blanka Holendova, Lydie Plecita-Hlavata
Summary: Redox status plays a crucial role in determining the fate of beta-cells, requiring proper signaling for differentiation, proliferation, and insulin expression. Chronic pathological insults can lead to dysfunction and glucose intolerance in beta-cells, ultimately resulting in cell death.
Article
Endocrinology & Metabolism
Sara McEwan, Hyokjoon Kwon, Azeddine Tahiri, Nivetha Shanmugarajah, Weikang Cai, Jin Ke, Tianwen Huang, Ariana Belton, Bhagat Singh, Le Wang, Zhiping P. Pang, Ercument Dirice, Esteban A. Engel, Abdelfattah El Ouaamari
Summary: The study reveals a sex difference in sensory innervation density in the pancreas, with male mice showing higher abundance of sensory neurons projecting in the pancreas. Sensory chemodenervation in male mice enhances glucose-stimulated insulin secretion and glucose clearance, with these metabolic benefits being influenced by sex hormones and potential gonadal hormone-independent mechanisms. Sex-biased nature of sensory control of islet beta-cell activity might be a result of neurodevelopmental inputs, sex hormone-dependent mechanisms, and the action of somatic molecules encoded by sex chromosome complement.
MOLECULAR METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Jo-Hsi Huang, Hannah K. C. Co, Yi-Chen Lee, Chia-Chou Wu, Sheng-hong Chen
Summary: The study reveals that the redox homeostasis in human cells is modulated by bistability, and that ROS exhibit switch-like responses during glucose deprivation. This ROS switch may be irreversible and exhibits hysteresis, providing important insights for quantitative investigations of redox regulation in humans.
MOLECULAR SYSTEMS BIOLOGY
(2021)
Article
Cell Biology
Jing Li, Yujing Zhang, Yangyang Ye, Dameng Li, Yuchen Liu, Eunyoung Lee, Mingliang Zhang, Xin Dai, Xiang Zhang, Shibei Wang, Junfeng Zhang, Weiping Jia, Ke Zen, Antonio Vidal-Puig, Xiaohong Jiang, Chen-Yu Zhang
Summary: This study reveals that pancreatic beta cell-released exosomal miR-29 family members regulate hepatic insulin sensitivity and glucose homeostasis. High levels of free fatty acids stimulate the secretion of miR-29s, which in turn impact insulin signaling in the liver.
JOURNAL OF EXTRACELLULAR VESICLES
(2021)
Review
Biochemistry & Molecular Biology
Alessandra Galli, Anoop Arunagiri, Nevia Dule, Michela Castagna, Paola Marciani, Carla Perego
Summary: Pancreatic beta-cells play a crucial role in glucose homeostasis by secreting insulin, and their dysfunction leads to diabetes. Cholesterol has gained significant attention as it not only controls beta-cell function but is also targeted by lipid-lowering therapies for diabetes-related cardiovascular complications. Understanding the mechanisms of cholesterol-mediated beta-cell function is still an area of exploration. Studies suggest that beta-cells regulate both total cholesterol levels and its distribution within organelles through vesicular and non-vesicular transport. This review aims to summarize the current understanding of cholesterol homeostasis in beta-cells and provide insights into the dynamic distribution of cholesterol among organelles to maintain their functionality, with a focus on early steps of insulin synthesis and secretion.
Review
Medicine, General & Internal
Zhe Zhang, Yunhan Tan, Canhua Huang, Xiawei Wei
Summary: DTP cells are a type of cells that can survive after exposure to anticancer drugs, and they enhance adaptive mutation by altering DNA repair mechanisms, resulting in the emergence of drug-resistant mutations. DTP cells maintain cellular homeostasis through metabolic reprogramming that promotes mitochondrial oxidative respiration and a robust antioxidant process, and they can resume proliferation after treatment withdrawal, leading to cancer relapse. Disrupting redox homeostasis by intervening with redox signaling is considered a promising therapeutic strategy. This review provides a comprehensive overview of the characteristics of DTP cells and the underlying mechanisms involved in redox signaling, aiming to offer a unique perspective on potential therapeutic applications based on their vulnerabilities to redox regulation.
Article
Biochemistry & Molecular Biology
Elena Klyosova, Iuliia Azarova, Stepan Buikin, Alexey Polonikov
Summary: This study identified the association between impaired redox homeostasis in the endoplasmic reticulum and proinsulin misfolding, leading to the activation of the unfolded protein response (UPR) and apoptosis in beta-cells, resulting in type 2 diabetes. The study also found differentially expressed genes (DEGs) involved in glutathione metabolism and their impact on protein folding and UPR in diabetic beta-cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Julia S. Ivanova, Olga G. Lyublinskaya
Summary: Pluripotent stem cells have metabolic plasticity and can adapt to both hypoxic and normoxic environments, and pluripotency is not strictly dependent on anaerobic conditions. The cellular redox homeostasis is similar between PSCs and many other somatic cells under in vitro conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Fisheries
Fangyuan Zhou, Lianlian Sun, Yina Shao, Xiumei Zhang, Chenghua Li
Summary: Glutaminolysis plays an important role in the immune response in Apostichopus japonicus. Decreased levels of glutaminolysis metabolic substrates and products were observed, accompanied by an increase in glutathione. The key genes in glutaminolysis were upregulated in response to pathogen infection. AMPK beta can regulate glutaminolysis by influencing the uptake of glutamine. Silencing AjAMPK beta leads to increased levels of glutamine and glutamate, decreased production of glutathione, and a reduction in redox homeostasis indexes.
FISH & SHELLFISH IMMUNOLOGY
(2022)
Article
Cell Biology
Lingyan Zhang, Jian Zhang, Yuanqing Jin, Gang Yao, Hai Zhao, Penghai Qiao, Shuguang Wu
Summary: Iron is essential for living cells and cancer cells have a high demand for it. However, iron can also stimulate the production of reactive oxygen species. Nrf2, an important factor in oxidative defense, is often overactivated in cancer cells and can promote cell proliferation and increase chemoresistance.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Jinxiang Wang, Leli Zeng, Nisha Wu, Yanling Liang, Jie Jin, Mingming Fan, Xiaoju Lai, Zhe-Sheng Chen, Yihang Pan, Fangyin Zeng, Fan Deng
Summary: In this study, it was discovered that high expression of PHGDH is associated with enzalutamide resistance in castration-resistant prostate cancer (CRPC) cells. Knockdown of PHGDH inhibited the growth of enzalutamide-resistant CRPC cells and sensitized them to enzalutamide treatment. Moreover, pharmacological inhibition of PHGDH induced ferroptosis and overcame enzalutamide resistance both in vitro and in vivo. Therefore, targeting PHGDH and inducing ferroptosis could be a potential therapeutic strategy for overcoming enzalutamide resistance in CRPC.
DRUG RESISTANCE UPDATES
(2023)
Article
Oncology
Shijia Wu, Yong Ai, Huimin Huang, Guangyu Wu, Shipeng Zhou, Weilong Hong, Percy David Papa Akuetteh, Guihua Jin, Xingling Zhao, Yihua Zhang, Xiaolong Zhang, Linhua Lan
Summary: This study demonstrates that B28 disrupts the YTHDF1-GLS1 axis to induce a ROS-dependent cell bioenergetics crisis and cell death, ultimately suppressing PAAD cell growth.
CANCER CELL INTERNATIONAL
(2022)
Review
Biochemistry & Molecular Biology
Elisabetta Catalani, Kashi Brunetti, Simona Del Quondam, Davide Cervia
Summary: This article discusses the relationship between mitochondrial dysfunction and retinal pathology related to RGC degeneration, as well as the potential for neuroprotection using redox-related strategies.
Review
Biochemistry & Molecular Biology
Yi-Hsuan Wu, Hsi-Lung Hsieh
Summary: Bioenergetic mitochondrial dysfunction is a common feature of various diseases, including Alzheimer's disease. Redox imbalance and mitochondrial dysfunction play important roles in the development of Alzheimer's disease. This review summarizes the evidence for redox imbalance and mitochondrial dysfunction in Alzheimer's disease, and discusses current therapeutic strategies related to mitochondrial maintenance.
Article
Biochemistry & Molecular Biology
Ilaria Coppola, Bas Brouwers, Sandra Meulemans, Bruno Ramos-Molina, John W. M. Creemers
Summary: FURIN cleaves the insulin receptor non-redundantly in beta cells, while redundantly in liver. The study demonstrated that the insulin receptor in beta cells plays a limited role in glucose homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Oleksandr Shapoval, Viktoriia Oleksa, Miroslav Slouf, Volodymyr Lobaz, Olga Trhlikova, Marcela Filipova, Olga Janouskova, Hana Engstova, Jan Pankrac, Adam Modry, Vit Herynek, Petr Jezek, Ludek Sefc, Daniel Horak
Summary: The study focused on developing nanoparticles for multimodal imaging, which displayed excellent colloidal stability in water and physiological buffers, showed no or only mild toxicity, and were efficiently internalized by various cells. These newly developed particles proved to be an effective contrast agent for multiple imaging techniques.
Review
Biochemistry & Molecular Biology
Petr Jezek, Blanka Holendova, Martin Jaburek, Jan Tauber, Andrea Dlaskova, Lydie Plecita-Hlavata
Summary: Pancreatic beta-cell insulin secretion is regulated by NADPH oxidase 4-mediated H2O2 production, requiring both ATP and H2O2 elevation to close the K-ATP channel. Additionally, simultaneous activation of other channels is necessary for the pulsatile exocytosis of insulin granule vesicles.
Article
Biochemistry & Molecular Biology
Petr Jezek, Blanka Holendova, Martin Jaburek, Andrea Dlaskova, Lydie Plecita-Hlavata
Summary: Mitochondria play a crucial role in glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells by increasing ATP synthesis. Recent studies have shown that mitochondrial redox signaling and Ca2+ influx are important for insulin secretion, while future research aims to further clarify these mechanisms.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Biochemistry & Molecular Biology
Pavla Pruchova, Klara Gotvaldova, Katarina Smolkova, Lukas Alan, Blanka Holendova, Jan Tauber, Alexander Galkin, Petr Jezek, Martin Jaburek
Summary: This study reveals the antioxidant and anti-inflammatory roles of iPLA(2)gamma in the brain. It demonstrates that iPLA(2)gamma is activated by tert-butylhydroperoxide and releases free fatty acids, which leads to an increase in respiratory rate and a decrease in mitochondrial superoxide production. It also shows that iPLA(2)gamma plays a key role in the remodeling of cardiolipins in the brain.
Meeting Abstract
Biochemistry & Molecular Biology
Petr Jezek, Blanka Holendova, Lydie Plecita-Hlavata, Pavla Pruchova, Hana Engstova, Martin Jaburek
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Blanka Holendova, Stepanka Benakova, Vojtech Pavluch, Jan Tauber, Petr Jezek, Lydie Plecita-Hlavata
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Min Li, Lydie Plecita-Hlavata, Evgenia Dobrinskikh, B. Alexandre McKeon, Aneta Gandjeva, Suzette Riddle, Aya Laux, Ram Raj Prasad, Sushil Kumar, Rubin M. Tuder, Hui Zhang, Cheng-Jun Hu, Kurt R. Stenmark
Summary: The study found that abnormal SIRT3 activity is related to mitochondrial dysfunction in adventitial fibroblasts from patients with pulmonary hypertension. Restoration of SIRT3 activity can reduce mitochondrial protein acetylation and restore mitochondrial function.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Petr Jezek, Martin Jaburek, Blanka Holendova, Hana Engstova, Andrea Dlaskova
Summary: The mitochondrial reticulum network in cells consists of parallel lamellar cristae formed by invaginated inner mitochondrial membrane. The non-invaginated part, the inner boundary membrane, forms a cylindrical sandwich with the outer mitochondrial membrane. The dimensions, shape, and junctions of cristae have characteristic patterns for different metabolic regimes, physiological and pathological situations.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Article
Biochemistry & Molecular Biology
Ippei Kawano, Bazila Bazila, Petr Jezek, Andrea Dlaskova
Summary: The architecture of the mitochondrial network and cristae critically impact cell differentiation and identity. Recent studies have shown that manipulating mitochondrial dynamics and cristae shape affects T cell phenotype, macrophage polarization, and other cellular processes. Further investigation of the molecular mechanisms involved could lead to improved therapeutic manipulation of cell viability, differentiation, proliferation, and identity.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Article
Multidisciplinary Sciences
Vojtech Pavluch, Tomas Spacek, Hana Engstova, Andrea Dlaskova, Petr Jezek
Summary: Using 3D-double-color direct stochastic optical reconstruction microscopy (dSTORM) and a new method of Delaunay segmentation of 3D data, we identified the presence of two or more mitochondrial DNA molecules in nucleoids in HeLa cells, indicating a low level of nucleoid division. This finding is important for understanding the organization and distribution of mitochondrial DNA.
SCIENTIFIC REPORTS
(2023)
Article
Immunology
Lydie Plecita-Hlavata, Andrea Brazdova, Monika Krivonoskova, Cheng-Jun Hu, Tzu Phang, Jan Tauber, Min Li, Hui Zhang, Konrad Hoetzenecker, Slaven Crnkovic, Grazyna Kwapiszewska, Kurt R. Stenmark
Summary: In pulmonary hypertension (PH), perivascular inflammation accompanied by pulmonary arterial remodeling is observed. This study aimed to investigate the contribution of pulmonary fibroblasts to the activation and polarization of T-cells in PH.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Endocrinology & Metabolism
Daniel Benak, Stepanka Benakova, Lydie Plecita-Hlavata, Marketa Hlavackova
Summary: The emerging field of epitranscriptomics has attracted attention due to its significant effects on gene expression and cellular physiology and pathophysiology. N-6-methyladenosine (m(6)A) and N-6,2'-O-dimethyladenosine (m(6)Am) are well-studied modifications in RNA that are dynamically regulated by epitranscriptomic regulators. Changes in m(6)A levels and regulatory proteins have been associated with diabetic tissues. This review provides an overview of the current knowledge on m(6)A and m(6)Am modifications and their regulators in the pathophysiology of diabetes mellitus, with a focus on type 2 diabetes and its treatment with metformin.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Petr Jezek
Summary: This article theoretically derives the mutual influence between mitochondria and the cytosol, predicting possible conditions for mitochondrial signals to the cytosol and plasma membrane. The involvement of peroxiredoxin 3 in mitochondrial-to-cytosol redox signaling is discussed, as well as the activation of matrix MnSOD in a specific case. The use of redox-sensitive probes and their impact on quantifying H2O2 fluxes is also considered.