Jian Liu
Deparment: Department of Biological Sciences

Items: 5

Views: 1664

1. Expression of Carbonic Anhydrase I in Motor Neurons and Alterations in ALS

Author:Liu, XC;Lu, DY;Bowser, R;Liu, J


Abstract:Carbonic anhydrase I (CA1) is the cytosolic isoform of mammalian alpha-CA family members which are responsible for maintaining pH homeostasis in the physiology and pathology of organisms. A subset of CA isoforms are known to be expressed and function in the central nervous system (CNS). CA1 has not been extensively characterized in the CNS. In this study, we demonstrate that CA1 is expressed in the motor neurons in human spinal cord. Unexpectedly, a subpopulation of CA1 appears to be associated with endoplasmic reticulum (ER) membranes. In addition, the membrane-associated CA1s are preferentially upregulated in amyotrophic lateral sclerosis (ALS) and exhibit altered distribution in motor neurons. Furthermore, long-term expression of CA1 in mammalian cells activates apoptosis. Our results suggest a previously unknown role for CA1 function in the CNS and its potential involvement in motor neuron degeneration in ALS.
2. Mechanical Behavior of Treated Timber Boardwalk Decks under Cyclic Moisture Changes


Source:Journal of the Korean Wood Science and Technology,2022,Vol.50

Abstract:Timber boardwalk decks are widely installed in parks and scenic areas to provide pedestrians an elevated footpath as well as harmony with the surrounding natural scene. In order to extend the lifespan of boardwalks in the outdoor environment, industrially treated pine timber, such as Pinus sylvestris, is often adopted. However, accidents of pedestrians injured by damaged boardwalk decks have been constantly reported. Therefore, the mechanical behavior of two different types of treated timber was examined in this study under repeated wetting and drying. An increasing number of radial cracks appeared with increasing length and width as more cycles were performed. A loss of more than 40%% of the screw withdrawal capacity was observed in both end grain and face grain for the two types of timber after twelve accelerated wet-dry cycles, which coincides with the observation of damaged timber boardwalks in the field investigation. At the same time, it was found that both the compressive and the flexural strength was not sensitive to the wet-dry cycles especially at large cycle numbers.
3. Dysfunction of Endocytic Kinase AAK1 in ALS

Author:Shi, BX;Conner, SD;Liu, J


Abstract:Mechanisms of human mutant superoxide dismutase 1 (SOD1)-induced toxicity in causing the familial form of amyotrophic lateral sclerosis (ALS) remain elusive. Identification of new proteins that can selectively interact with mutant SOD1s and investigation of their potential roles in ALS are important to discover new pathways that are involved in disease pathology. Using the yeast two-hybrid system, we identified the adaptor-associated kinase 1 (AAK1), a regulatory protein in clathrin-coated vesicle endocytic pathway that selectively interacted with the mutant but not the wild-type SOD1. Using both transgenic mouse and rat SOD1-linked familial ALS (FALS) models, we found that AAK1 was partially colocalized with the endosomal and presynaptic protein markers under the normal physiological condition, but was mislocated into aggregates that contained mutant SOD1s and the neurofilament proteins in rodent models of ALS in disease. AAK1 protein levels were also decreased in ALS patients. These results suggest that dysfunction of a component in the endosomal and synaptic vesicle recycling pathway is involved in ALS pathology.
4. Ensnaring membrane type 1-matrix metalloproteinase (MT1-MMP) with tissue inhibitor of metalloproteinase (TIMP)-2 using the haemopexin domain of the protease as a carrier: a targeted approach in cancer inhibition

Author:Jiang, BJ;Zhang, Y;Liu, J;Tsigkou, A;Rapti, M;Lee, MH


Abstract:Metastatic cancer cells express Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) to degrade the extracellular matrix in order to facilitate migration and proliferation. Tissue Inhibitor of Metalloproteinase (TIMP)-2 is the endogenous inhibitor of the MMP. Here, we describe a novel and highly effective fusion strategy to enhance the delivery of TIMP-2 to MT1-MMP. We can reveal that TIMP-2 fused to the haemopexin +/- transmembrane domains of MT1-MMP (two chimeras named T2(PEX+TM) and T2(PEX)) are able to interact with MT1-MMP on the cell surface as well as intracellularly. In the case of T2(PEX+TM), there is even a clear sign of MT1-MMP: T2(PEX+TM) aggregation by the side of the nucleus to form aggresomes. In vitro, T2(PEX+TM) and T2(PEX) suppress the gelatinolytic and invasive abilities of cervical carcinoma (HeLa) and HT1080 fibrosarcoma cancer cells significantly better than wild type TIMP-2. In mouse xenograft, we further demonstrate that T2(PEX) diminishes cervical carcinoma growth by 85%% relative to the control. Collectively, our findings indicate the effectiveness of the fusion strategy as a potential targeted approach in cancer inhibition.
5. Targeting a Designer TIMP-1 to the Cell Surface for Effective MT1-MMP Inhibition: A Potential Role for the Prion Protein in Renal Carcinoma Therapy

Author:Jiang, BJ;Liu, J;Lee, MH


Abstract:Renal carcinoma cells express Membrane Type 1-Matrix Metalloproteinase (MT1-MMP, MMP-14) to degrade extracellular matrix components and a range of bioactive molecules to allow metastasis and cell proliferation. The activity of MT1-MMP is modulated by the endogenous inhibitors, Tissue Inhibitor of Metalloproteinases (TIMPs). In this study, we describe a novel strategy that would enable a designer TIMP-1 tailored specifically for MT1-MMP inhibition (V4A/P6V/T98L; K-i(app) 1.66 nM) to be targeted to the plasma membrane for more effective MT1-MMP inhibition. To achieve this, we fuse the designer TIMP-1 to the glycosyl-phosphatidyl inositol (GPI) anchor of the prion protein to create a membrane-tethered, high-affinity TIMP variant named T1(Pr MT1) that is predominantly located on the cell surface and co-localised with MT1-MMP. Confocal microscopy shows that T1(Pr MT1) is found throughout the cell surface in particular the membrane ruffles where MT1-MMP is most abundant. Expression of T1(Pr MT1) brings about a complete abrogation of the gelatinolytic activity of cellular MT1-MMP in HT1080 fibrosarcoma cells whilst in renal carcinoma cells CaKi-1, the GPI-TIMP causes a disruption in MMP-mediated proteolysis of ECM components such as fibronectin, collagen I and laminin that consequently triggers a downstream senescence response. Moreover, the transduced cells also suffer from an impairment in proliferation and survival in vitro as well as in NOD/SCID mouse xenograft. Taken together, our findings demonstrate that the GPI anchor of prion could be exploited as a targeting device in TIMP engineering for MT1-MMP inhibition with a potential in renal carcinoma therapy.
Total 5 results found
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