Article
Neurosciences
David Perez-Boyero, Carlos Hernandez-Perez, Jorge Valero, Valeria Lorena Cabedo, Jose Ramon Alonso, David Diaz, Eduardo Weruaga
Summary: The main olfactory bulb (MOB) is a neural structure that processes olfactory information. Nitric oxide (NO), produced mainly by neuronal nitric oxide synthase (nNOS), plays a crucial role in the plasticity and functioning of the MOB. The absence of nNOS expression in nNOS-KO mice leads to a reduced olfactory capacity, while an increase in the expression of endothelial nitric oxide synthase (eNOS) is observed. However, the level of NO generated in the MOB does not appear to change significantly. These findings suggest that nNOS is essential for the proper functioning of the olfactory system.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Chemistry, Analytical
Fang Tang, Chang Gao, Jin-Yu Liu, Zhong-Lin Lu, Lan He, Ai-Xiang Ding
Summary: A new sensor, Lyso-DHP, was designed and synthesized for sensitive and selective detection of NO in lysosomes of living cells. This sensor exhibited fast response, high ?switch-on? ratio, low detection limit, and cytocompatibility. Localization studies confirmed its high specificity, precision, and brightness for tracing subcellular NO.
SENSORS AND ACTUATORS B-CHEMICAL
(2021)
Article
Medicine, General & Internal
Sylvia Lee-Huang, Philip Lin Huang, Paul Lee Huang
Summary: The genetic knockdown of endothelial nitric oxide synthase (eNOS) inhibits mitochondrial biogenesis and adipogenesis in human mesenchymal stem cells (hMSCs), with mitochondrial transfer restoring adipogenesis in eNOS-deficient cells. Live-cell real-time imaging provides insights into the relationship between mitochondrial biogenesis and adipogenesis in stem cell differentiation. The results suggest that mitochondrial remodeling could be a potential therapeutic approach for conditions like obesity and diabetes.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Shuhan Bu, Hien C. Nguyen, Sepideh Nikfarjam, David C. R. Michels, Berk Rasheed, Sauraish Maheshkumar, Shweta Singh, Krishna K. Singh
Summary: The endothelium maintains vascular homeostasis by balancing vasorelaxation and vasoconstriction through regulating Nitric Oxide (NO) availability. Endothelial nitric oxide synthase (eNOS) is involved in this process and regulates endothelial function such as cell proliferation, migration, and tube formation. Inhibition of eNOS through genetic or pharmacologic methods has shown differential effects on endothelial cell behavior, suggesting a more complex mechanism behind eNOS regulation.
Article
Chemistry, Medicinal
Zhirong Ouyang, Muye Ma, Kai Yin, Nan Guo, Wei Fu, Wei Guo, Xianfeng Gu
Summary: This paper presents the development of an activatable fluorescent nanoprobe, BOD-NH-NP, for detecting endogenous nitric oxide (NO). The probe shows fast responding reaction towards NO and incorporates a BODIPY fluorescent dye with good optical features, making it applicable for detecting endogenous NO in living cells and screening nitric oxide synthases (NOSs) inhibitors and agonists.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Analytical
Hong Wang, Guangmei Han, Hesen Tang, Ruilong Zhang, Zhengjie Liu, Yingqiang Sun, Bianhua Liu, Junlong Geng, Zhongping Zhang
Summary: Fluorescence microscopy is an important tool in cell biology research, but its use for long-term and strong-illumination imaging of live cells is limited by photobleaching and phototoxicity. This study introduces a new concept of fluorophore engineering chemistry, using synchronous photoactivation-imaging (SPI) fluorophores to overcome these limitations. The SPI fluorophores allow continuous replenishing of bright-state probes and reduce photocytotoxicity, enabling long-term imaging of live cells under intensive illumination.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Su Liang, Zeyu Wang, Luyu Qi, Chao Tang, Yiming Zhang, Qun Luo, Yayun Wu, Jinghe Yuan, Yao Zhao, Yanyan Zhang, Xiaohong Fang, Shijun Wang, Fuyi Wang
Summary: This study designed a fluorescent probe, ATTO565-WGN, which showed similar anti-proliferative activity to wogonin against human cancer cell lines and demonstrated mitochondrial localization through confocal fluorescence imaging. The conjugated ATTO565 fluorophore enabled STED fluorescence living cell imaging with ultrahigh spatial resolution, facilitating the investigation of wogonin-biological target interactions in living cells at mitochondria. This work provides novel insights into rational design of mitochondrion targeting fluorescence probes for ultrahigh resolution living cell imaging.
Article
Biotechnology & Applied Microbiology
Andreas Boden, Francesca Pennacchietti, Giovanna Coceano, Martina Damenti, Michael Ratz, Ilaria Testa
Summary: A new 3D pRESOLFT microscope method with sub-80-nm resolution has been developed to visualize the volumetric architecture of organelles and molecules inside whole living cells, allowing for targeted 3D confinement of fluorescence and observation of dynamic structural alterations in cells.
NATURE BIOTECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Tracy L. Smith, Malika Oubaha, Gael Cagnone, Cecile Boscher, Jin Sung Kim, Yassine El Bakkouri, Ying Zhang, Rony Chidiac, Jeanne Corriveau, Chantal Delisle, Gregor U. Andelfinger, Przemyslaw Sapieha, Jean-Sebastien Joyal, Jean-Philippe Gratton
Summary: The study indicates that inhibition of eNOS alters the polarity program of endothelial cells, leading to increased cell polarization, regulated sprouting angiogenesis, and normalized pathological neovascularization during retinopathy.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Wenshuo Xie, Nianhong Xing, Jicheng Qu, Dongwu Liu, Qiuxiang Pang
Summary: This review summarizes the structure, isoforms, and physiological role of CAPON, as well as its relationship with heart diseases, diabetes, psychiatric disorders, and tumors. The C-terminal PDZ-binding motif of CAPON plays a regulatory role in nitric oxide production and neuronal development. Clarifying the future research directions on the signal pathways related to CAPON will facilitate the study of its regulatory mechanism and provide new ideas for treating human diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Rachel Wills, Jonathan Farhi, Patrick Czabala, Sophia Shahin, Jennifer M. Spangle, Monika Raj
Summary: Aliphatic aldehydes are reactive electrophilic carbonyls that cross-link with DNA and proteins leading to cellular toxicity and disease pathogenesis. Chemical sensors that generate a benzimidazole moiety upon reaction with aliphatic aldehydes of different chain lengths have been developed, enabling the real-time imaging and quantification of aldehyde formation in live mammalian cells. This tool has the potential to revolutionize aldehyde research by uncovering cellular metabolites that have previously remained elusive.
Article
Cardiac & Cardiovascular Systems
Sarah E. Basehore, Samantha Bohlman, Callie Weber, Swathi Swaminathan, Yuji Zhang, Cholsoon Jang, Zoltan Arany, Alisa Morss Clyne
Summary: The study found that steady laminar flow reduces eNOS O-GlcNAcylation by limiting glycolysis and the availability of UDP-GlcNAc, leading to increased eNOS phosphorylation and NO production. This research demonstrates for the first time that O-GlcNAcylation is regulated by mechanical stimuli, which has implications for cardiovascular disease.
CIRCULATION RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Miriam M. Cortese-Krott, Tatsiana Suvorava, Francesca Leo, Sophia K. Heuser, Anthea LoBue, Junjie Li, Stefanie Becher, Rebekka Schneckmann, Tanu Srivrastava, Ralf Erkens, Georg Wolff, Joachim P. Schmitt, Maria Grandoch, Jon O. Lundberg, John Pernow, Brant E. Isakson, Eddie Weitzberg, Malte Kelm
Summary: This study reveals that red blood cell endothelial nitric oxide synthase (RBC eNOS) plays a role in limiting infarct size in acute myocardial infarction (AMI) and regulates coronary blood flow and cardiac function. These findings suggest that RBC eNOS signaling may represent a novel target for interventions in ischemia/reperfusion after myocardial infarction.
Article
Cardiac & Cardiovascular Systems
Francesca Leo, Tatsiana Suvorava, Sophia K. Heuser, Junjie Li, Anthea LoBue, Frederik Barbarino, Eugenia Piragine, Rebekka Schneckmann, Beate Hutzler, Miranda E. Good, Bernadette O. Fernandez, Lukas Vornholz, Stephen Rogers, Allan Doctor, Maria Grandoch, Johannes Stegbauer, Eddie Weitzberg, Martin Feelisch, Jon O. Lundberg, Brant E. Isakson, Malte Kelm, Miriam M. Cortese-Krott
Summary: This study demonstrates that eNOS in ECs and RBCs independently contribute to blood pressure homeostasis. EC eNOS KO mice exhibited significantly impaired aortic dilatory responses to acetylcholine, loss of flow-mediated dilation, and increased blood pressure. On the other hand, RBC eNOS KO mice showed no alterations in acetylcholine-mediated dilation or flow-mediated dilation but were hypertensive.
Article
Chemistry, Physical
Zhenzhen Lu, Luke W. Giles, Rico F. Tabor, Boon Mian Teo
Summary: The study fabricated NE-derived CDs with green luminescence, showing pH and concentration dependent fluorescence behavior. The multiple functional groups on the CDs allow them to alter fluorescence intensity and peak position in different pH conditions, demonstrating significant potential for live-cell imaging and blood sample detection. Additionally, a simple and effective method based on the inner filter effect was developed to determine the concentration of hemoglobin in diluted human blood samples, showing good linearity and a low limit of determination.
Article
Cardiac & Cardiovascular Systems
Fotios Spyropoulos, Andrea Sorrentino, Jiska van der Reest, Peiran Yang, Markus Waldeck-Weiermair, Benjamin Steinhorn, Emrah Eroglu, Seyed Soheil Saeedi Saravi, Paul Yu, Marcia Haigis, Helen Christou, Thomas Michel
Summary: In this study, we developed a chemogenetic animal model of heart failure that mimics a central feature of human heart failure: increased cardiac redox stress. By using recombinant DAAO enzyme to generate H2O2 in cardiomyocytes, we induced cardiomyopathy. We observed significant changes in cardiac metabolome and transcriptome following chemogenetic heart failure, similar to those observed in human heart failure. Our findings help validate chemogenetic approaches for discovering novel therapeutic targets in heart failure.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2022)
Article
Cell Biology
Benjamin Gottschalk, Corina T. Madreiter-Sokolowski, Wolfgang F. Graier
Summary: This article focuses on the synergistic control of OPA1 and MICU1 on the cristae junction, highlighting the critical role of the adaptive cristae junction permeability in regulating various mitochondrial functions. Specifically, it discusses the impact of MICU1-regulated cristae junction on the activity and distribution of MCU within the complex ultrastructure of mitochondria.
Article
Biology
Zhanat Koshenov, Furkan E. Oflaz, Martin Hirtl, Benjamin Gottschalk, Rene Rost, Roland Malli, Wolfgang F. Graier
Summary: The study investigates the regulation of basal mitochondrial bioenergetics and reveals that Ca2+ fluxes from ER-mitochondria contact sites control basal mitochondrial metabolism and energetics. The researchers identify citrin as a primary regulator of this process and show that manipulation of Ca2+ dynamics can reprogram cellular and mitochondrial metabolism.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sandra Burgstaller, Helmut Bischof, Lucas Matt, Robert Lukowski
Summary: Cancer is a major cause of death globally, and understanding the molecular mechanisms behind the disease is crucial. Altered K+ channel expression is frequently associated with various types of cancer, impacting malignancy and disease outcomes. However, the precise roles of oncogenic K+ channels in cell physiology, homeostasis, and subcellular compartments are not well understood. Genetically encoded fluorescent biosensors provide a non-invasive approach to simultaneously investigate metabolic and ionic signaling in individual cells and organelles, allowing for a high-resolution study of compartmentalized metabolite or ion dynamics. These versatile tools have been used to visualize and understand the subcellular consequences of aberrant K+ channel expression and activity in K+ channel-related cancer research.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Ines Tawfik, Benjamin Gottschalk, Angelo Jarc, Doruntina Bresilla, Rene Rost, Barbara Obermayer-Pietsch, Wolfgang F. Graier, Corina T. Madreiter-Sokolowski
Summary: Thyroid hormones regulate mitochondrial Ca2+ uptake, leading to increased energy metabolism and reactive oxygen species production.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Hematology
Arvind K. Pandey, Markus Waldeck-Weiermair, Quinn S. Wells, Wusheng Xiao, Shambhu Yadav, Emrah Eroglu, Thomas Michel, Joseph Loscalzo
Summary: This study reveals that CD70 plays a regulatory role in endothelial NO and reactive oxygen species homeostasis and is associated with vascular phenotypes. CD70 knockdown leads to reduced NO levels and increased reactive oxygen species, which may be related to endothelial dysfunction and cardiovascular diseases, highlighting its significance in human vascular diseases.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Transplantation
Andras T. Deak, Katarina Belic, Anna-Maria Meissl, Katharina Artinger, Kathrin Eller, Bernd Rechberger, Tobias Niedrist, Wolfgang F. Graier, Roland Malli, Helmut Bischof, Sandra Burgstaller, Sandra Blass, Alexander Avian, Alexander R. Rosenkranz, Alexander H. Kirsch
Summary: This study assessed the performance of genetically encoded potassium-ion indicators (GEPIIs) in measuring salivary potassium concentration and found that salivary potassium levels exhibited similar kinetics to plasma potassium levels. However, further research is needed to determine if saliva could be a suitable sample type for monitoring plasma potassium levels.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Cell Biology
Furkan E. Oflaz, Zhanat Koshenov, Martin Hirtl, Olaf A. Bachkoenig, Wolfgang F. Graier, Benjamin Gottschalk
Summary: Mitochondrial uncoupling proteins UCP1 and UCP2 have different molecular mechanisms for executing their mitochondria uncoupling function, with UCP1 dissipating the proton motive force and UCP2 modulating the permeability of the cristae junction. This mini-review discusses the molecular mechanisms of UCP1 in brown adipose tissue and UCP2 in aged and cancer non-excitable cells, and the synergistic effects of both UCPs with the mitochondrial Ca2+ uptake machinery.
Article
Genetics & Heredity
Lukas Kaufmann, Johannes Pilic, Lisa Auinger, Anna-Lena Mayer, Jasmin Blatterer, Johann Semmler-Bruckner, Safdar Abbas, Khurram Rehman, Muhammad Ayaz, Wolfgang F. Graier, Roland Malli, Erwin Petek, Klaus Wagner, Ali Al Kaissi, Muzammil Ahmad Khan, Christian Windpassinger
Summary: Restrictive dermopathy (RD) is a lethal condition caused by loss-of-function mutations in ZMPSTE24, while mutations preserving residual enzymatic activity lead to mandibuloacral dysplasia with type B lipodystrophy (MADB) phenotype. A new homozygous loss-of-function mutation in ZMPSTE24 was identified in two consanguineous Pakistani families with MADB. Functional analysis revealed that alternative translation initiation sites were utilized, preventing complete loss of protein function and explaining the relatively mild phenotype in affected patients. Our findings suggest considering the creation of new potential start codons in other disease-associated genes with N-terminal mutations.
Article
Biochemistry & Molecular Biology
Madeleine Goeritzer, Katharina B. Kuentzel, Sarah Beck, Melanie Korbelius, Silvia Rainer, Ivan Bradic, Dagmar Kolb, Marion Mussbacher, Waltraud C. Schrottmaier, Alice Assinger, Axel Schlagenhauf, Rene Rost, Benjamin Gottschalk, Thomas O. Eichmann, Thomas Zuellig, Wolfgang F. Graier, Nemanja Vujic, Dagmar Kratky
Summary: Monoglyceride lipase (MGL) hydrolyzes monoacylglycerols (MG) and plays a role in platelet function. MGL deficiency leads to decreased platelet aggregation and impaired response to collagen activation, resulting in reduced thrombus formation and prolonged bleeding time. Genetic deletion of MGL is associated with altered thrombogenesis in mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Asal Ghaffari Zaki, Seyed Mohammad Miri, Seyma Cimen, Tuba Akgul Caglar, Esra N. Yigit, Mehmet S. Aydin, Gurkan Ozturk, Emrah Eroglu
Summary: pH-Control is a novel enzymatic method that allows precise control of ultralocal acidification in living cells. The genetically encoded biosensor SypHer3s demonstrated that pH-Control effectively acidifies cytosolic, mitochondrial, and nuclear pH in a concentration-dependent manner. This approach shows promise in investigating the ultralocal pH imbalance associated with various diseases.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Editorial Material
Cell Biology
Benjamin Gottschalk, Roland Malli, Wolfgang F. Graier
Summary: Changes in mitochondrial ultrastructure and dynamics, including cytochrome c release, membrane potential rearrangement, and mitochondrial Ca2+ uptake dynamics, are observed in MICU1(-/-) cells due to its sensitivity to Ca2+ and its binding to Mic60 and CHCHD2. MICU1 is not only an interaction partner and regulator of the MCU complex, but also plays a crucial role in determining mitochondrial ultrastructure and initiating apoptosis.
Article
Chemistry, Multidisciplinary
Zuzana Klepcova, Ivana Spakova, Corina T. T. Madreiter-Sokolowski, Wolfgang Graier, Katarina Kalinova, Erika Samolova, Romana Smolkova, Lukas Smolko, Miroslava Rabajdova
Summary: Two novel Mn(II) complexes with fenamic acid and flufenamic acid as ligands and neocuproine as a supporting ligand were synthesized and characterized. The complexes exhibit moderate radical scavenging activity and cytotoxic effects on selected cell lines, with the flufenamic acid complex being able to induce apoptosis. Both complexes target inflammatory processes on a cellular level.
NEW JOURNAL OF CHEMISTRY
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Z. Klepcova, I. Spakova, L. Smolko, M. Marekova, W. F. Graier, M. Rabajdova
Article
Biochemistry & Molecular Biology
Julia Claudiane da Veiga, Neidiquele Maria Silveira, Amedea Barozzi Seabra, Ilana Urbano Bron
Summary: This review investigates the strategy of using nitric oxide (NO) donors to extend postharvest shelf-life and improve fruit quality, discusses the interactions between NO and ethylene or reactive oxygen species, and highlights the potential of nanotechnology in NO applications.
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
(2024)