Wang M.,Tongji University |
Cheng L.,Translational Center for Stem Cell Research |
Li Q.,Shanghai University |
Chen Z.,Shanghai University |
Wang S.,Tongji University
Physical Chemistry Chemical Physics | Year: 2014
Three-dimensional (3D) flower-like hausmannite architectures of Mn3O4 with uniform morphology have been successfully synthesized by a novel chemical reaction route using cetyltrimethylammonium bromide as the template. Micro/nanostructures of the as-synthesized 3D flower-like Mn3O4 architectures were investigated in detail by a series of analytical techniques. The geometrical shape of 3D flower-like Mn3O4 architectures is structurally perfect, and they are produced with diameters in the range of several hundred nanometers to a few micrometers. Experimental results indicate that two-dimensional nanosheets associated with one-dimensional single-crystalline nanorods self-assembled into three-dimensional flower-like Mn3O4 architectures. The single-crystalline Mn3O4 nanorods are a few hundred nanometers long and several tens of nanometers wide. Different dimensional systems, such as two-dimensional nanosheets, one-dimensional nanorods, and three-dimensional nanoflowers, could provide different building blocks to constitute nanostructured materials. These specific building blocks, which constituted the complex hierarchical architectures with nanostructural features, may offer exciting opportunities for both fundamental research and technological applications. © the Partner Organisations 2014.
Fan Y.,Baylor College of Medicine |
Shi Y.,Baylor College of Medicine |
Liu S.,Translational Center for Stem Cell Research |
Liu S.,Tongji University |
And 9 more authors.
Cellular Signalling | Year: 2012
Protein kinases are important regulators of intracellular signal transduction pathways and play critical roles in diverse cellular processes. TAK1, a member of the MAPKKK family, is essential for TNFα-induced NF-κB activation. Phosphorylation and Lys 63-linked polyubiquitination (polyUb) of TAK1 are critical for its activation. However, whether TAK1 is regulated by polyubiquitination-mediated protein degradation after its activation remains unknown. Here we report that TNFα induces TAK1 Lys 48 linked polyubiquitination and degradation at the later time course. Furthermore, we provide direct evidence that TAK1 is modified by Lys 48-linked polyubiquitination at lysine-72 by mass spectrometry. A K72R point mutation on TAK1 abolishes TAK1 Lys 48-linked polyubiquitination and enhances TAK1/TAB1 co-overexpression-induced NF-κB activation. As expected, TAK1 K72R mutation inhibits TNFα-induced Lys 48-linked TAK1 polyubiquitination and degradation. TAK1 K72R mutant prolongs TNFα-induced NF-κB activation and enhances TNFα-induced IL-6 gene expression. Our findings demonstrate that TNFα induces Lys 48-linked polyubiquitination of TAK1 at lysine-72 and this polyubiquitination-mediated TAK1 degradation plays a critical role in the downregulation of TNFα-induced NF-κB activation. © 2012 Elsevier Inc..
Fan Y.,Baylor College of Medicine |
Fan Y.,Translational Center for Stem Cell Research |
Mao R.,Baylor College of Medicine |
Yu Y.,Baylor College of Medicine |
And 17 more authors.
Journal of Experimental Medicine | Year: 2014
Lys63-linked polyubiquitination of RIG-I is essential in antiviral immune defense, yet the molecular mechanism that negatively regulates this critical step is poorly understood. Here, we report that USP21 acts as a novel negative regulator in antiviral responses through its ability to bind to and deubiquitinate RIG-I. Overexpression of USP21 inhibited RNA virus-induced RIG-I polyubiquitination and RIG-I-mediated interferon (IFN) signaling, whereas deletion of USP21 resulted in elevated RIG-I polyubiquitination, IRF3 phosphorylation, IFN-α/β production, and antiviral responses in MEFs in response to RNA virus infection. USP21 also restricted antiviral responses in peritoneal macrophages (PMs) and bone marrow-derived dendritic cells (BMDCs). USP21-deficient mice spontaneously developed splenomegaly and were more resistant to VSV infection with elevated production of IFNs. Chimeric mice with USP21-deficient hematopoietic cells developed virus-induced splenomegaly and were more resistant to VSV infection. Functional comparison of three deubiquitinases (USP21, A20, and CYLD) demonstrated that USP21 acts as a bona fide RIG-I deubiquitinase to down-regulate antiviral response independent of the A20 ubiquitinediting complex. Our studies identify a previously unrecognized role for USP21 in the negative regulation of antiviral response through deubiquitinating RIG-I. © 2014 Fan et al.
Jin X.,Soochow University of China |
Liu J.,Translational Center for Stem Cell Research |
Liu W.,Shenzhen University
Current Neurovascular Research | Year: 2014
Tissue plasminogen activator (tPA) thrombolysis, remains to be the only United States Food and Drug Administration (FDA) approved treatment for acute ischemia stroke. However, the use of tPA has been profoundly constrained due to its narrow therapeutic time window and the increased risk of potentially deadly hemorrhagic complications. TPA-Associated hemorrhagic transformation (HT) often occurs as a result of catastrophic failure of the blood brain barrier (BBB), wherein the affected cerebral capillaries can no longer hold blood constituents. Due to its direct contribution to edema and HT, reperfusion-Associated BBB damage has been extensively studied, while BBB damage that occurs within the thrombolytic time window is largely neglected. Of note, ischemia-induced BBB damage in the early stroke stages is increasingly appreciated to negatively affect the safety and efficacy profiles of thrombolytic therapy for ischemic stroke. In this review, we discussed the recent findings of spatio-temporal evolution of BBB injury in the early stages of cerebral ischemia and its association with intracerebral hemorrhage following tPA thrombolysis. The increased understanding of early ischemic BBB damage and its close link to tPA-Associated HT is of particular importance for developing new preventive and therapeutic strategies to reduce the hemorrhagic complications in stroke thrombolysis. © 2014 Bentham Science Publishers.
Zhang J.,Fudan University |
Zhang J.,Tongji University |
Zhang J.,Translational Center for Stem Cell Research |
Zhou Y.,Tongji University |
And 10 more authors.
Current Molecular Medicine | Year: 2013
MicroRNAs (miRNAs) are a class of small non-encoding RNAs that regulate gene expression at the posttranscriptional level. MiRNAs may characterize not only specific stages of the development of the neural cell population in CNS, but also distinct types of neural cells. However, the common pathways of the neural enriched miRNAs involved in neurogenesis of specific cell lineages remain poorly understood. In this report, in order to get insights into the common role of the miRNAs shared by cerebellum and forebrain, we studied the regulatory mechanism of neural enriched-miRNA in neural progenitor cell (NPCs) differentiation. Here, we identified a new cerebellum-enriched rno-miR-592 in rat cerebellum. It showed that rno-miR-592 was a neuralenriched miRNA and may play an important role in rat embryonic neurogenesis or/and astrogliogenesis. We used both gain-of -function and loss-of -function approaches to demonstrate that rno-miR-592 could change the balance between neuron- and astrocyte- like differentiation and neuronal morphology. We observed that miR-592 could induce astrogliogenesis differentiation arrest or/and enhance neurogenesis in vitro. Meanwhile, silencing of miR-592 was not beneficial for neuronal maturation. We also identified Lrrc4c and Nfasc as miR- 592 target genes, and miR-592 could affect the changes of Lrrc4c and Nfasc expression levels, suggesting that these two target genes may be involved in miR-592 regulative function in NPCs differentiation and neuronal maturation. Thus, we conclude that rno-miR-592 may affect the neural lineage differentiation via reducing astrogliogenesis or/and enhancing neurogenesis at least in part through regulating its target genes Lrrc4c and Nfasc in vitro. Together, we report here for the first time the important role of miR-592 in rat NPCs differentiation and neuronal maturation. © 2013 Bentham Science Publishers.