Article
Cell Biology
Thanh Nha Uyen Le, Toan Q. Nguyen, Pazhanichamy Kalailingam, Yen Thi Kim Nguyen, Viresh Krishnan Sukumar, Clarissa Kai Hui Tan, Farhana Tukijan, Ludovic Couty, Zafrul Hasan, Ilaria Del Gaudio, Markus R. Wenk, Amaury Cazenav-Gassot, Eric Camerer, Long N. Nguyen
Summary: This study highlights the importance of S1P transporters Mfsd2b and Spns2 in maintaining vascular integrity and homeostasis. Global deletion of these transporters leads to embryonic lethality, while postnatal deletion increases susceptibility to anaphylaxis in mice.
Article
Cell Biology
Martyna Okuniewska, Victoria Fang, Audrey Baeyens, Varsha Raghavan, June-Yong Lee, Dan R. Littman, Susan R. Schwab
Summary: The text discusses the role of S1P receptor 1 in T cell exit from lymph nodes and vascular permeability regulation. It also highlights the therapeutic potential of targeting S1PR1 for autoimmune diseases. The importance of SPNS2 in supplying lymph S1P and supporting T cell exit is emphasized, but further research is needed to determine its necessity during immune responses.
Article
Biochemistry & Molecular Biology
Chao Fang, Pan Ren, Ganlan Bian, Jian Wang, Jiaxin Bai, Jiaxing Huang, Yixiao Ding, Xueyong Li, Mingkai Li, Zheng Hou
Summary: Sepsis is a major cause of in-hospital mortality, and understanding the metabolic reprogramming of macrophages and its impact on immune response is crucial for sepsis research. This study identified Spns2 as a key metabolic mediator in regulating inflammation through the lactate-ROS axis. Spns2 deficiency enhances glycolysis and intracellular lactate production, leading to increased pro-inflammatory response and hyperinflammation in early sepsis, as well as immunosuppression in the late stage of infection.
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)
Article
Chemistry, Medicinal
Christopher W. Shrader, Daniel Foster, Yugesh Kharel, Tao Huang, Kevin R. Lynch, Webster L. Santos
Summary: Sphingosine-1-phosphate (S1P) is a chemotactic lipid that affects immune cell positioning. Inhibition of S1P transport by Spns2 may be a potential target for the treatment of inflammation and autoimmune diseases.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Grzegorz Mlynarczyk, Agnieszka Miklosz, Jaroslaw Suchanski, Safoura Reza, Lech Romanowicz, Krzysztof Sobolewski, Adrian Chabowski, Marcin Baranowski
Summary: This study provides detailed data on sphingolipid metabolism in different stages of clear cell renal cell carcinoma (ccRCC), showing significant alterations in sphingolipid content in tumors compared to healthy tissue, with changes correlated with malignancy grades. The dysregulation of sphingolipid metabolism may contribute to the progression of ccRCC.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Geok-Lin Chua, Bryan C. Tan, Randy Y. J. Loke, Menglan He, Cheen-Fei Chin, Bernice H. Wong, Alvin C. Y. Kuk, Mei Ding, Markus R. Wenk, Lan Guan, Federico Torta, David L. Silver
Summary: Mfsd2a is a sodium-dependent lysophosphatidylcholine transporter expressed at the blood-brain barrier that is crucial for omega-3 fatty acid transport and brain development. Although the transport mechanism of Mfsd2a has been proposed through cryo-EM structures, the biochem-ical evidence of flippase activity and sodium-dependent LPC inversion is still lacking. In this study, an in vitro assay using recombinant Mfsd2a reconstituted in liposomes was established to demonstrate the flipping of lysophosphatidylserine (LPS) from the outer to the inner leaflet of a membrane bilayer in a sodium-dependent manner. Through cryo-EM structures, mutagenesis, and cell-based transport assay, amino acid residues important for Mfsd2a activity were identified, providing direct biochemical evidence of Mfsd2a functioning as a lysolipid flippase.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Engineering, Biomedical
Xiufeng Ju, Tongtong Miao, Haiyan Chen, Jiang Ni, Liang Han
Summary: Mfsd2a plays a crucial role in regulating the transcytosis and permeability of the blood-brain barrier. Strategies involving priming nanoparticles and drug-loaded nanoparticles have shown promising results in enhancing BBB crossing efficiency and brain accumulation of therapeutics for breast cancer brain metastases.
ADVANCED HEALTHCARE MATERIALS
(2021)
Article
Multidisciplinary Sciences
Shaoting Zheng, Hongqi Wang, Jingxia Han, Xintong Dai, Ying Lv, Tao Sun, Huijuan Liu
Summary: This study evaluated the changes of ImP-producing bacteria on the skin and found that the abundance of ImP-producing bacteria-Streptococcus is significantly increased in the intestine and skin of T2DM mice. It was found that ImP can inhibit the formation of blood vessels in the process of wound healing by inhibiting S1P secretion and the activation of the Rho signaling pathway, which affects angiogenesis.
Review
Biochemistry & Molecular Biology
David Martin-Hernandez, Marina Munoz-Lopez, Hiram Tendilla-Beltran, Javier R. Caso, Borja Garcia-Bueno, Luis Menchen, Juan C. Leza
Summary: Extensive research has shown the importance of immune alterations and dysfunctional biological barriers in psychiatric disorders. The leaky gut phenomenon, closely related to the brain and intestinal barriers, may contribute to inflammation in these conditions. Drugs based on sphingosine-1-phosphate (S1P), such as fingolimod and ozanimod, have been approved for multiple sclerosis and ulcerative colitis treatment, sparking a debate for their use in psychiatry. This review focuses on the molecular mechanisms of S1P in modulating the immune system and brain/intestinal barriers, aiming to uncover innovative therapies for psychiatric diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Toan Q. Nguyen, Thiet Minh Vu, Farhana Tukijan, Sneha Muralidharan, Juat Chin Foo, Jasmine Fei Li Chin, Zafrul Hasan, Federico Torta, Long N. Nguyen
Summary: Erythrocytes efficiently uptake exogenous sphingosine for S1P production, with a de novo synthesis pathway also contributing to provide sphingosine. SphK1 plays a key role in facilitating sphingosine uptake by converting it into S1P in erythrocytes, with this process being irreversible. Mfsd2b utilizes a proton gradient to release S1P and its transport activity is dependent on negatively charged residues D95 and T157.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Physiology
Jong-Heon Kim, Jin Han, Kyoungho Suk
Summary: The blood-brain barrier (BBB) is crucial for maintaining brain homeostasis, and the protein C8G plays an important role in protecting BBB integrity by inhibiting neuroinflammation. This highlights a novel mechanism of astrocyte-EC cross talk in BBB maintenance during inflammation.
FRONTIERS IN PHYSIOLOGY
(2021)
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.
Review
Neurosciences
Krishan B. Atreya, Julie D. Saba
Summary: This article describes the neurological manifestations of SPL insufficiency syndrome (SPLIS) caused by SGPL1 mutations and summarizes insights into the neurological consequences of SPL insufficiency from studies of brain-specific SPL knockout mice and Drosophila SPL mutants.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Medicine, General & Internal
William J. Sandborn, Severine Vermeire, Laurent Peyrin-Biroulet, Marla C. Dubinsky, Julian Panes, Andres Yarur, Timothy Ritter, Filip Baert, Stefan Schreiber, Sheldon Sloan, Fabio Cataldi, Kevin Shan, Christopher J. Rabbat, Michael Chiorean, Douglas C. Wolf, Bruce E. Sands, Geert D'Haens, Silvio Danese, Martina Goetsch, Brian G. Feagan
Summary: Etrasimod, a selective S1P receptor modulator, demonstrated efficacy and safety as an induction and maintenance therapy for patients with moderately to severely active ulcerative colitis. The trials showed a higher proportion of patients achieving clinical remission with Etrasimod compared to placebo at both induction and maintenance periods. This novel treatment option has the potential to address unmet needs in ulcerative colitis patients.
Article
Cell Biology
Qiang Xie, Jun Zeng, Yongtao Zheng, Tianwen Li, Junwei Ren, Kezhu Chen, Quan Zhang, Rong Xie, Feng Xu, Jianhong Zhu
Summary: The study suggests that mitochondrial transplantation may alleviate cerebral ischemia-reperfusion injury by potentially involving mitochondrial component separation, altering cellular metabolism, reducing ROS and apoptosis. Additionally, the way of isolated mitochondrial transfer into the cell may be related to intercellular connection.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2021)
Article
Clinical Neurology
Nai-Li Wei, Zi-Fang Quan, Tong Zhao, Xu-Dong Yu, Qiang Xie, Jun Zeng, Fu-Kai Ma, Fan Wang, Qi-Sheng Tang, Heng Wu, Jian-Hong Zhu
NEUROPSYCHIATRIC DISEASE AND TREATMENT
(2019)