Article
Biochemistry & Molecular Biology
Xinyue Guo, Yinan Meng, Yumiao Wang, Shifa Nan, Yuchen Lu, Dezhang Lu, Yupeng Yin
Summary: Hypoxic pulmonary hypertension (HPH) is a respiratory disease characterized by increased pulmonary vascular resistance and pulmonary arterial pressure. This study found that type 3 inositol-1,4,5-trisphosphate receptor (IP3R3) plays a key role in HPH. Knockdown of IP3R3 can inhibit the abnormal function of hypoxia-induced pulmonary arterial endothelial cells and prevent the development of HPH.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Alfred Hausladen, Zhaoxia Qian, Rongli Zhang, Richard T. Premont, Jonathan S. Stamler
Summary: Research has shown that loading SNO onto Hb in mouse RBCs can promote vasodilation under hypoxia. However, S-nitrosylation of Hb within intact mouse RBCs is ineffective, and levels of metHb are high. An optimized method for SNO loading in mouse RBCs has been developed, and it has been shown that loss of SNO loading in mutant RBCs results in reduced vasodilation. The stoichiometry of SNO/met/nitrosyl Hb can account for differences in RBC function among studies.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2022)
Article
Cardiac & Cardiovascular Systems
Xiaofei Zhou, Yuanqing Jiang, Yuewen Wang, Linge Fan, Yunhui Zhu, Yefeng Chen, Yiran Wang, Yingyi Zhu, Hongkun Wang, Zihang Pan, Zhoubin Li, Xiaolong Zhu, Ruizhe Ren, Zhen Ge, Dongwu Lai, En Yin Lai, Ting Chen, Kai Wang, Ping Liang, Lingfeng Qin, Cuiqing Liu, Cong Qiu, Michael Simons, Luyang Yu
Summary: This study found that the FIS1 protein in endothelial mitochondria undergoes a transition between SUMOylation and deSUMOylation in hypoxia-induced pulmonary hypertension (PH). Short-term hypoxia promotes the translocation of SENP1 to endothelial mitochondria and deSUMOylation of FIS1, maintaining mitochondrial integrity and calcium communication. Prolonged hypoxia inhibits this process, leading to mitochondrial dysfunction and metabolic reprogramming.
CIRCULATION RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Karen Flores, Patricia Siques, Julio Brito, Silvia M. Arribas
Summary: AMP-activated protein kinase (AMPK) plays an important role in hypoxic pulmonary hypertension by participating in cardiovascular protection and inhibiting pulmonary artery wall overgrowth pathways, potentially serving as a therapeutic target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Yi Ye, Qiying Xu, Tana Wuren
Summary: Hypoxic pulmonary hypertension (HPH) is a complex vascular disorder characterized by elevated blood pressure in the lungs. It is driven by the reprogramming of gene expression patterns, leading to cellular metabolism, inflammation, and proliferation. Hypoxia plays a key role in HPH by promoting immune/inflammatory processes that control vascular remodeling. However, many animal models used to study HPH may not accurately represent the human disease state and are not suitable for testing new therapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Wenjie Tao, Alina Yerbulekova, Curtis E. Moore, Hannah S. Shafaat, Shiyu Zhang
Summary: The interconversion between metal-S-nitrosothiol adduct and metal nitrosyl thiolate complex can regulate the direction of reversible S-(de)nitrosation. This process is sensitive to temperature, solvent coordination ability, and counterions, and copper centers can modulate the bond formation and cleavage through minor perturbations of the local environment.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Yujie Jiang, Yingfan Guo, Xuexiang Feng, Pingting Yang, Yi Liu, Xuejing Dai, Feilong Zhao, Dongyu Lei, Xiaohui Li, Yuan Liu, Ying Li
Summary: This study aimed to investigate the effects of BMP signaling on iron metabolism and its implication in hypoxia-induced PH. The results showed that iron deficiency promoted oxidative stress and apoptosis in HPAECs in hypoxia-induced PH, and enhanced expression of hepcidin regulated by BMP6/BMPR2 signaling may contribute to iron metabolic disorder.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Medicine, Research & Experimental
Yuhan Qin, Yong Qiao, Linqing Li, Erfei Luo, Dong Wang, Yuyu Yao, Chengchun Tang, Gaoliang Yan
Summary: This study demonstrates that METTL3 plays a crucial role in the development of hypoxia-induced PASMCs proliferation by mediating m(6)A modification on PTEN mRNA. The METTL3/YTHDF2/PTEN axis represents a significant pathway in HPH, offering a new potential therapeutic target.
Article
Cardiac & Cardiovascular Systems
Rui Wang, Jinjin Pan, Jinzhen Han, Miaomiao Gong, Liang Liu, Yunlong Zhang, Ying Liu, Dingyou Wang, Qing Tang, Na Wu, Lin Wang, Jinsong Yan, Hua Li, Yuhui Yuan
Summary: This study demonstrates that melatonin can alleviate dasatinib-aggravated hypoxic pulmonary hypertension by inhibiting pulmonary vascular remodeling and protecting endothelial cells and inhibiting abnormal proliferation of smooth muscle cells.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Gizem Kayki-Mutlu, Walter J. Koch
Summary: Cardiac diseases, especially heart failure, are the leading cause of morbidity and mortality globally. The loss of beta-adrenoceptor-mediated inotropic reserve and the elevated activities of G protein-coupled receptor kinases and beta-arrestins after heart injury/stress play significant roles in heart failure. Nitric oxide produced by NO synthase enzymes modulates GPCR regulators profoundly through S-nitrosylation, independent of its canonical signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Physiology
Martha Hinton, James A. Thliveris, Grant M. Hatch, Shyamala Dakshinamurti
Summary: This study investigated the effects of sodium nitroprusside (NO donor) in treating hypoxic persistent pulmonary hypertension in newborns. The results showed that sodium nitroprusside can reduce reactive oxygen species accumulation, enhance cell relaxation, and inhibit adenylyl cyclase activity. Additionally, sodium nitroprusside can decrease protein nitrosylation levels. These findings provide insights into the reduced effectiveness of NO treatment in hypoxic pulmonary hypertension.
FRONTIERS IN PHYSIOLOGY
(2023)
Review
Chemistry, Medicinal
Patryk Remiszewski, Barbara Malinowska
Summary: The use of cannabinoids as potential drugs for hypertension is still uncertain and further research is needed to determine their efficacy.
Article
Cell Biology
Hui Sun, Omkar Paudel, James S. K. Sham
Summary: This study provides evidence for altered intracellular Cl- homeostasis in PA smooth muscle cells associated with chronic hypoxic pulmonary hypertension, suggesting the important role of chloride transporters in regulating the Cl- concentration in pulmonary arterial smooth muscle cells.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Richard T. Premont, James D. Reynolds, Rongli Zhang, Jonathan S. Stamler
Summary: Red blood cell-mediated vasodilation is crucial for oxygen delivery, facilitated by the conversion of heme-bound nitric oxide into vasodilator S-nitrosothiol. This process is regulated by a strictly conserved Cys residue in hemoglobin. The model of a three-gas respiratory cycle (O-2/NO/CO2) is supported by the coupling of hemoglobin allostery to NO conversion and SNO release.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Pharmacology & Pharmacy
Shaokun Chen, Xiaozhen Wei, Xu Zhang, Mengge Yao, Zhihuang Qiu, Liangwan Chen, Li Zhang
Summary: Tex261 is downregulated in pulmonary artery hypertension (PAH) and its decreased expression is associated with cell proliferation and vessel remodeling. Elevating Tex261 expression can have preventive and therapeutic effects on PAH.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Richard T. Premont, James D. Reynolds, Rongli Zhang, Jonathan S. Stamler
Summary: Red blood cell-mediated vasodilation is crucial for oxygen delivery, facilitated by the conversion of heme-bound nitric oxide into vasodilator S-nitrosothiol. This process is regulated by a strictly conserved Cys residue in hemoglobin. The model of a three-gas respiratory cycle (O-2/NO/CO2) is supported by the coupling of hemoglobin allostery to NO conversion and SNO release.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Editorial Material
Biochemistry & Molecular Biology
Richard T. Premont
Article
Radiology, Nuclear Medicine & Medical Imaging
Alexandra Badea, Robert Schmalzigaug, Woojoo Kim, Pamela Bonner, Umer Ahmed, G. Allan Johnson, Gary Cofer, Mark Foster, Robert J. Anderson, Cristian Badea, Richard T. Premont
Summary: GIT1-KO mice exhibit neuroimaging phenotypes such as microcephaly and altered cortical layering, with a decrease in neuron density in cortical layer V. High field MRM revealed reduced white matter volume, particularly in the anterior commissure, in GIT1-KO mice. The basal ganglia appeared enlarged in GIT1-KO mice, suggesting a vulnerability to addiction.
MAGNETIC RESONANCE IMAGING
(2021)
Review
Endocrinology & Metabolism
Hua-Lin Zhou, Richard T. Premont, Jonathan S. Stamler
Summary: This review discusses the crucial role of S-nitrosylation in the regulation of insulin signaling throughout the insulin life cycle, impacting both metabolic health and disease. The interplay between insulin signaling and protein S-nitrosylation is highlighted, with aberrant S-nitrosylation contributing to metabolic disorders such as type 2 diabetes mellitus. Understanding the impact of S-nitrosylation on cellular metabolism could provide valuable insights in the field of metabolic signaling and insulin-related disorders.
NATURE REVIEWS ENDOCRINOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Richard T. Premont, David J. Singel, Jonathan S. Stamler
Summary: This chapter reviews the crucial role of hemoglobin in carrying and releasing SNO in the autoregulation of blood flow, and its physiological and pathological implications for oxygen delivery. Additionally, therapeutic opportunities to optimize oxygen delivery at the level of tissue blood flow are highlighted.
MOLECULAR ASPECTS OF MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Daniel M. Fass, Michael C. Lewis, Rushdy Ahmad, Matthew J. Szucs, Qiangge Zhang, Morgan Fleishman, Dongqing Wang, Myung Jong Kim, Jonathan Biag, Steven A. Carr, Edward M. Scolnick, Richard T. Premont, Stephen J. Haggarty
Summary: This study aims to elucidate the molecular and cellular basis of cognitive deficits in schizophrenia. The research found that genetic variations in a set of genes involved in regulating neuroplasticity may contribute to cognitive deficits and exert their effects by perturbing the networks of these genes.
MOLECULAR PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Fabio Fonseca, Thomas M. Raffay, Kunhong Xiao, Precious J. McLaughlin, Zhaoxia Qian, Zachary W. Grimmett, Naoko Adachi, Benlian Wang, Alfred Hausladen, Brian A. Cobb, Rongli Zhang, Douglas T. Hess, Benjamin Gaston, Nevin A. Lambert, James D. Reynolds, Richard T. Premont, Jonathan S. Stamler
Summary: S-Nitrosylation is a central mechanism in β(2)-adrenergic receptor signaling, essential for both classic desensitization by PKA and NO-based signaling that mediates bronchorelaxation. Mutant β(2)AR refractory to S-nitrosylation amplifies NO-based signaling, leading to resistance to bronchoconstriction and asthma development.
Article
Cell Biology
Colin T. Stomberski, Nicholas M. Venetos, Hua-Lin Zhou, Zhaoxia Qian, Bryce R. Collison, Seth J. Field, Richard T. Premont, Jonathan S. Stamier
Summary: Accumulating evidence indicates that protein S-nitrosylation is regulated by enzymes, and specificity in S-nitrosylation is derived from dedicated S-nitrosylases and denitrosylases. In this study, mice deficient in the protein denitrosylase SCoR2 showed reduced serum cholesterol due to decreased secretion of the cholesterol-regulating protein PCSK9. The researchers found that SCoR2 controls an S-nitrosylation cascade involving SAR1 and SURF4, which act as S-nitrosylases, to inhibit PCSK9 secretion. These findings suggest a potential treatment paradigm for cardiovascular disease.
Article
Urology & Nephrology
Julian Gerhards, Lars D. Maerz, Edda S. F. Matthees, Cornelia Donow, Barbara Moepps, Richard T. Premont, Martin D. Burkhalter, Carsten Hoffmann, Melanie Philipp
Summary: This study identifies GRK4 as a novel regulator of cilia and kidney development, independent of its kinase function. The GRK4 variants believed to act as hyperactive kinases are dysfunctional for normal ciliogenesis, suggesting a receptor-independent mechanism.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Divya Seth, Colin T. Stomberski, Precious J. McLaughlin, Richard T. Premont, Kathleen Lundberg, Jonathan S. Stamler
Summary: The aim of this study was to investigate the interactions between nitric oxide synthase (NOS) isoforms and proteins, as well as the mechanisms by which they mediate S-nitrosylation. The results showed that each NOS isoform interacts with and S-nitrosylates many proteins, but a large proportion of S-nitrosylated proteins are not associated with NOS. Additionally, the interactomes and S-nitrosylomes of individual NOS isoforms are largely unique, indicating specific roles for each isoform in S-nitrosylation.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Article
Chemistry, Medicinal
Hua-Lin Zhou, Alfred Hausladen, Puneet Anand, Malligarjunan Rajavel, Colin T. Stomberski, Rongli Zhang, Richard T. Premont, William J. Greenlee, Focco van den Akker, Jonathan S. Stamler
Summary: Acute kidney injury (AKI) is a serious condition with high morbidity and mortality, and there are currently no drugs available for treatment. However, the deletion of S-nitrosocoenzyme A reductase 2 (SCoR2; AKR1A1) has been found to protect mice against AKI through metabolic reprogramming, suggesting that SCoR2 could be a potential drug target.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Puneet Seth, Richard T. Premont, Jonathan S. Stamler
Summary: Post-translational modification by S-nitrosylation plays a key role in regulating cellular functions and impacting proteins across phylogeny. The protocol described focuses on isolating S-nitrosylated proteins from C. elegans, with potential for adaptation to mammalian tissues. Protecting SNO proteins from degradation remains a major challenge in this protocol.
Letter
Multidisciplinary Sciences
Songling Liu, Louis M. Luttrell, Richard T. Premont, Don C. Rockey
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)