Article
Biochemistry & Molecular Biology
Michela Terlizzi, Chiara Colarusso, Giusy Ferraro, Anna Falanga, Maria Chiara Monti, Pasquale Somma, Ilaria De Rosa, Luigi Panico, Aldo Pinto, Rosalinda Sorrentino
Summary: Sex is a biological variable that can affect the activity of the lipid mediator S1P in lung conditions. This study found sex differences in circulating S1P levels among lung cancer patients, with ADK patients having lower levels compared to SCC patients. Additionally, the expression of S1P receptors and metabolic enzymes differed between male and female patients with different lung cancer types. These findings highlight the importance of considering sex differences when studying S1P as a prognostic mediator in lung cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Vikas Satyananda, Masanori Oshi, Yoshihisa Tokumaru, Aparna Maiti, Nitai Hait, Ryusei Matsuyama, Itaru Endo, Kazuaki Takabe
Summary: High S1P export, driven by the simultaneous high expression of SphK1 and ABCC1, is associated with enhanced HCC progression and immune response, leading to significantly worse disease-specific survival and overall survival outcomes.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Cell Biology
Michela Terlizzi, Chiara Colarusso, Pasquale Somma, Ilaria De Rosa, Luigi Panico, Aldo Pinto, Rosalinda Sorrentino
Summary: This study revealed that S1P plays a role in promoting inflammation and cytokine release in non-small cell lung cancer patients, emphasizing its role as a pro-tumor driver.
Article
Cell Biology
Chiara D'Aprile, Simona Prioni, Laura Mauri, Alessandro Prinetti, Sara Grassi
Summary: Lipid rafts are specialized membrane domains enriched in gangliosides, sphingomyelin, cholesterol, and proteins involved in signal transduction, modulating cell homeostasis. Sphingosine 1-phosphate participates in various signal transduction processes, with enzymes and receptors often localized in lipid rafts.
CELLULAR SIGNALLING
(2021)
Review
Pharmacology & Pharmacy
Gerhild van Echten-Deckert
Summary: Lipids are essential components of the CNS, and sphingolipids, a type of lipid, are highly concentrated in the brain. Sphingosine 1-phosphate (S1P), derived from membrane sphingolipids, has complex effects on the brain, which can be both beneficial and detrimental. However, the role of S1P in brain development and various brain pathologies is still controversial.
PHARMACOLOGY & THERAPEUTICS
(2023)
Review
Biochemistry & Molecular Biology
Celine Tolksdorf, Eileen Moritz, Robert Wolf, Ulrike Meyer, Sascha Marx, Sandra Bien-Moeller, Ulrike Garscha, Gabriele Jedlitschky, Bernhard H. Rauch
Summary: Sphingosine-1-phosphate (S1P) is a versatile signaling lipid that regulates various cellular processes. Platelets are an important source of S1P and can rapidly generate and release it to regulate cellular responses. Furthermore, platelet-generated and released S1P may also impact disease processes such as inflammation-driven vascular diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Michela Terlizzi, Chiara Colarusso, Anna Falanga, Pasquale Somma, Ilaria De Rosa, Luigi Panico, Aldo Pinto, Piera Maiolino, Rosalinda Sorrentino
Summary: This study investigated the interaction between S1P and STING in the lung during inflammatory conditions. The mRNA levels of ASAH1, the precursor enzyme of S1P, and STING were correlated inversely in healthy lung tissues but positively in tumor tissues. The activation of STING led to increased expression of ASAH1 and the release of IFN-beta and IL-6. In lung cancer patients, high levels of STING and ASAH1 mRNA were associated with a poor prognosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Colin Niaudet, Bongnam Jung, Andrew Kuo, Steven Swendeman, Edward Bull, Takahiro Seno, Reed Crocker, Zhongjie Fu, Lois E. H. Smith, Timothy Hla
Summary: This study reveals the significance of S1P in vascular development. Activation of endothelial S1PR1 by circulating HDL-S1P can suppress neovascularization in retinopathy. These findings suggest that circulating HDL-S1P activation of endothelial S1PR1 serves as a protective mechanism against neovascular retinopathy.
EMBO MOLECULAR MEDICINE
(2023)
Article
Multidisciplinary Sciences
Leiye Yu, Licong He, Bing Gan, Rujuan Ti, Qingjie Xiao, Hongli Hu, Lizhe Zhu, Sheng Wang, Ruobing Ren
Summary: This study reveals the activation and regulation mechanism of human S1PR1 receptor through cryo-electron microscopy analysis. The S1PR1 receptor plays an essential role in the immune and vascular systems, and understanding its function in depth contributes to the development of related therapeutic approaches.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Shah Alam, Sumaiya Yasmeen Afsar, Gerhild Van Echten-Deckert
Summary: In this study, the neural-targeted ablation of SGPL1 in a mouse model revealed that the accumulation of S1P due to SGPL1 deficiency led to increased expression of glycolytic enzymes, preferential entry of pyruvate into the TCA cycle, and elevated cellular ATP content. The high energy load activated mTOR, thus regulating astrocytic autophagy and potentially affecting neuronal viability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Xuefeng Xu, Yi Han, Tianxin Zhu, Faxin Fan, Xin Wang, Yuqing Liu, Duosheng Luo
Summary: Osteoporosis is a common disease worldwide with significant economic burden. Understanding the role of SphK/S1P/S1PR signaling in regulating osteoblasts and osteoclasts is crucial for the treatment of osteoporosis. This review summarizes the effects of S1P on proliferation, differentiation, apoptosis, and functions, and focuses on S1P-based therapeutic approaches in bone metabolism.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Zafrul Hasan, Toan Q. Nguyen, Brenda Wan Shing Lam, Jovi Hui Xin Wong, Caleb Cheng Yi Wong, Clarissa Kai Hui Tan, Jiabo Yu, Chung Hwee Thiam, Yongliang Zhang, Veronique Angeli, Long N. Nguyen
Summary: The protein Spns2 is involved in regulating lymphocyte movement and has been shown to have potential as a drug target in autoimmune diseases. This study examined mice with a genetic deletion of Spns2 and found that it affected lymphocyte levels, S1P secretion, and lymph node vasculature. Additionally, these mice were resistant to multiple sclerosis, suggesting that targeting Spns2 could be a promising therapeutic approach for neuroinflammation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Oncology
Eileen M. McGowan, Yiguang Lin, Size Chen
Summary: Obesity is closely associated with inflammation and increased cancer risk in the digestive system. Saturated fat diets and being overweight can cause chronic inflammation. Bioactive sphingolipids, signaling molecules made from saturated fats, play essential roles in maintaining healthy gastrointestinal immunity. Excessive levels of these molecules can lead to chronic inflammation, but drugs that block their activity have the potential to reduce gastrointestinal cancer risk.
Article
Neurosciences
Huitong Song, Holly P. McEwen, Thomas Duncan, Jun Yup Lee, Jonathan D. Teo, Anthony S. Don
Summary: SphK2 deficiency leads to decreased remyelination and maintenance of myelin with aging, possibly due to elevated levels of cytotoxic sphingosine and ceramide.
Article
Cell Biology
Yuan Yuan, Guowen Jia, Chao Wu, Wei Wang, Lin Cheng, Qian Li, Ziyan Li, Kaidong Luo, Shengyong Yang, Wei Yan, Zhaoming Su, Zhenhua Shao
Summary: This study presents five cryo-electron microscopy structures of S1PRs bound to diverse drug agonists and the heterotrimeric Gi protein. The structural and functional assays demonstrate the different binding modes of chemically distinct agonists of S1PRs, reveal the mechanical switch that activates these receptors, and provide a framework for understanding ligand selectivity and G protein coupling.