Medicine and Health Sciences Commons^™

Adaptation Mechanism And Tolerance Of Rhodopseudomonas Palustris Psb-S Under Pyrazosulfuron-Ethyl Stress, Xiang-Wen Luo, De-Yang Zhang, Teng-Hui Zhu, Xuguo Zhou, Jing Peng, Song-Bai Zhang, Yong Liu

Entomology Faculty Publications

Background: Pyrazosulfuron-ethyl is a long lasting herbicide in the agro-ecosystem and its residue is toxic to crops and other non-target organisms. A better understanding of molecular basis in pyrazosulfuron-ethyl tolerant organisms will shed light on the adaptive mechanisms to this herbicide.

Results: Pyrazosulfuron-ethyl inhibited biomass production in Rhodopseudomonas palustris PSB-S, altered cell morphology, suppressed flagella formation, and reduced pigment biosynthesis through significant suppression of carotenoids biosynthesis. A total of 1127 protein spots were detected in the two-dimensional gel electrophoresis. Among them, 72 spots representing 56 different proteins were found to be differently expressed using MALDI-TOF/TOF-MS, including 26 up- and 30 …

Hdl In Endocrine Carcinomas: Biomarker, Drug Carrier, And Potential Therapeutic, Emily E. Morin, Xiang-An Li, Anna Schwendeman

Physiology Faculty Publications

High-density lipoprotein (HDL) have long been studied for their protective role against cardiovascular diseases, however recently relationship between HDL and cancer came into focus. Several epidemiological studies have shown an inverse correlation between HDL-cholesterol (HDL-C) and cancer risk, and some have even implied that HDL-C can be used as a predictive measure for survival prognosis in for specific sub-population of certain types of cancer. HDL itself is an endogenous nanoparticle capable of removing excess cholesterol from the periphery and returning it to the liver for excretion. One of the main receptors for HDL, scavenger receptor type B-I (SR-BI), is highly …

Modulation Of Auxin And Cytokinin Responses By Early Steps Of The Phenylpropanoid Pathway, Jasmina Kurepa, Timothy E. Shull, Sumudu S. Karunadasa, Jan A. Smalle

Plant and Soil Sciences Faculty Publications

Background: The phenylpropanoid pathway is responsible for the synthesis of numerous compounds important for plant growth and responses to the environment. In the first committed step of phenylpropanoid biosynthesis, the enzyme phenylalanine ammonia-lyase (PAL) deaminates L-phenylalanine into trans-cinnamic acid that is then converted into p-coumaric acid by cinnamate-4-hydroxylase (C4H). Recent studies showed that the Kelch repeat F-box (KFB) protein family of ubiquitin ligases control phenylpropanoid biosynthesis by promoting the proteolysis of PAL. However, this ubiquitin ligase family, alternatively named Kiss Me Deadly (KMD), was also implicated in cytokinin signaling as it was shown to promote the degradation of …

Rna Binding Proteins Co-Localize With Small Tau Inclusions In Tauopathy, Brandon F. Maziuk, Daniel J. Apicco, Anna Lourdes Cruz, Lulu Jiang, Peter E. A. Ash, Edroaldo Lummertz De Rocha, Cheng Zhang, Wai Haung Yu, John Leszyk, Jose F. Abisambra, Hu Li, Benjamin Wolozin

Sanders-Brown Center on Aging Faculty Publications

The development of insoluble, intracellular neurofibrillary tangles composed of the microtubule-associated protein tau is a defining feature of tauopathies, including Alzheimer’s disease (AD). Accumulating evidence suggests that tau pathology co-localizes with RNA binding proteins (RBPs) that are known markers for stress granules (SGs). Here we used proteomics to determine how the network of tau binding proteins changes with disease in the rTg4510 mouse, and then followed up with immunohistochemistry to identify RNA binding proteins that co-localize with tau pathology. The tau interactome networks revealed striking disease-related changes in interactions between tau and a multiple RBPs, and biochemical fractionation studies demonstrated …

High-Density Lipoprotein Inhibits Serum Amyloid A-Mediated Reactive Oxygen Species Generation And Nlrp3 Inflammasome Activation, Preetha Shridas, Maria C. De Beer, Nancy R. Webb

Internal Medicine Faculty Publications

Serum amyloid A (SAA) is a high-density apolipoprotein whose plasma levels can increase more than 1000-fold during a severe acute-phase inflammatory response and are more modestly elevated in chronic inflammation. SAA is thought to play important roles in innate immunity, but its biological activities have not been completely delineated. We previously reported that SAA deficiency protects mice from developing abdominal aortic aneurysms (AAAs) induced by chronic angiotensin II (AngII) infusion. Here, we report that SAA is required for AngII-induced increases in interleukin-1β (IL-1β), a potent proinflammatory cytokine that is tightly controlled by the Nod-like receptor protein 3 (NLRP3) inflammasome and …

Visualizing Mutation-Specific Differences In The Trafficking-Deficient Phenotype Of Kv11.1 Proteins Linked To Long Qt Syndrome Type 2, Allison R. Hall, Corey L. Anderson, Jennifer L. Smith, Tooraj Mirshahi, Samy-Claude Elayi, Craig T. January, Brian P. Delisle

Physiology Faculty Publications

KCNH2 encodes the Kv11.1 α-subunit that underlies the rapidly activating delayed-rectifier K⁺ current in the heart. Loss-of-function KCNH2 mutations cause long QT syndrome type 2 (LQT2), and most LQT2-linked missense mutations inhibit the trafficking of Kv11.1 channel protein to the cell surface membrane. Several trafficking-deficient LQT2 mutations (e.g., G601S) generate Kv11.1 proteins that are sequestered in a microtubule-dependent quality control (QC) compartment in the transitional endoplasmic reticulum (ER). We tested the hypothesis that the QC mechanisms that regulate LQT2-linked Kv11.1 protein trafficking are mutation-specific. Confocal imaging analyses of HEK293 cells stably expressing the trafficking-deficient LQT2 mutation F805C showed that, …

Morphoregulatory Functions Of The Rna-Binding Motif Protein 3 In Cell Spreading, Polarity And Migration, J. Pilotte, W. Kiosses, S. W. Chan, H. P. Makarenkova, Esther E. Dupont-Versteegden, P. W. Vanderklish

Physical Therapy Faculty Publications

RNA-binding proteins are emerging as key regulators of transitions in cell morphology. The RNA-binding motif protein 3 (RBM3) is a cold-inducible RNA-binding protein with broadly relevant roles in cellular protection, and putative functions in cancer and development. Several findings suggest that RBM3 has morphoregulatory functions germane to its roles in these contexts. For example, RBM3 helps maintain the morphological integrity of cell protrusions during cell stress and disease. Moreover, it is highly expressed in migrating neurons of the developing brain and in cancer invadopodia, suggesting roles in migration. We here show that RBM3 regulates cell polarity, spreading and migration. RBM3 …

Matrix Metalloproteinase-Mediated Blood-Brain Barrier Dysfunction In Epilepsy, Ralf G. Rempe, Anika M. S. Hartz, Emma L. B. Soldner, Brent S. Sokola, Satya R. Alluri, Erin L. Abner, Richard J. Kryscio, Anton Pekcec, Juli Schlichtiger, Björn Bauer

Pharmaceutical Sciences Faculty Publications

The blood-brain barrier is dysfunctional in epilepsy, thereby contributing to seizure genesis and resistance to antiseizure drugs. Previously, several groups reported that seizures increase brain glutamate levels, which leads to barrier dysfunction. One critical component of barrier dysfunction is brain capillary leakage. Based on our preliminary data, we hypothesized that glutamate released during seizures mediates an increase in matrix-metalloproteinase (MMP) expression and activity levels, thereby contributing to barrier leakage. To test this hypothesis, we exposed isolated brain capillaries from male Sprague Dawley rats to glutamate ex vivo and used an in vivo/ex vivo approach of isolated brain capillaries …

Role Of Protein Charge Density On Hepatitis B Virus Capsid Formation, Xinyu Sun, Dong Li, Zhaoshuai Wang, Panchao Yin, Rundong Hu, Rundong Hu, Hui Li, Qiao Liu, Yunyi Gao, Baiping Ren, Jie Zheng, Yinan Wei, Tianbo Liu

Chemistry Faculty Publications

The role of electrostatic interactions in the viral capsid assembly process was studied by comparing the assembly process of a truncated hepatitis B virus capsid protein Cp149 with its mutant protein D2N/D4N, which has the same conformational structure but four fewer charges per dimer. The capsid protein self-assembly was investigated under a wide range of protein surface charge densities by changing the protein concentration, buffer pH, and solution ionic strength. Lowering the protein charge density favored the capsid formation. However, lowering charge beyond a certain point resulted in capsid aggregation and precipitation. Interestingly, both the wild-type and D2N/D4N mutant displayed …

Transmembrane Domains Of Highly Pathogenic Viral Fusion Proteins Exhibit Trimeric Association In Vitro, Stacy R. Webb, Stacy E. Smith, Michael G. Fried, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Enveloped viruses require viral fusion proteins to promote fusion of the viral envelope with a target cell membrane. To drive fusion, these proteins undergo large conformational changes that must occur at the right place and at the right time. Understanding the elements which control the stability of the prefusion state and the initiation of conformational changes is key to understanding the function of these important proteins. The construction of mutations in the fusion protein transmembrane domains (TMDs) or the replacement of these domains with lipid anchors has implicated the TMD in the fusion process. However, the structural and molecular details …

A Lin28b Tumor-Specific Transcript In Cancer, Weijie Guo, Zhixiang Hu, Yichao Bao, Yuchen Li, Shengli Li, Qiupeng Zheng, Dongbin Lyu, Di Chen, Tao Yu, Yan Li, Xiaodong Zhu, Jie Ding, Yingjun Zhao, Xianghuo He, Shenglin Huang

Markey Cancer Center Faculty Publications

The diversity and complexity of the cancer transcriptome may contain transcripts unique to the tumor environment. Here, we report a LIN28B variant, LIN28B-TST, which is specifically expressed in hepatocellular carcinoma (HCC) and many other cancer types. Expression of LIN28B-TST is associated with significantly poor prognosis in HCC patients. LIN28B-TST initiates from a de novo alternative transcription initiation site that harbors a strong promoter regulated by NFYA but not c-Myc. Demethylation of the LIN28B-TST promoter might be a prerequisite for its transcription and transcriptional regulation. LIN28B-TST encodes a protein isoform with additional N-terminal amino acids and is critical for cancer …

Neurotensin Receptor 3/Sortilin Contributes To Tumorigenesis Of Neuroendocrine Tumors Through Augmentation Of Cell Adhesion And Migration, Ji Tae Kim, Dana L. Napier, Heidi L. Weiss, Eun Y. Lee, Courtney M. Townsend, B. Mark Evers

Markey Cancer Center Faculty Publications

Neurotensin (NTS), a 13–amino acid peptide which is distributed predominantly along gastrointestinal tract, has multiple physiologic and pathologic functions, and its effects are mediated by three distinct NTS receptors (NTSRs). Overexpression and activation of NTS signaling components, especially NTS and/or NTSR1, are closely linked with cancer progression and metastasis in various types of cancers including neuroendocrine tumors (NETs). Although deregulation of NTSR3/sortilin has been implicated in a variety of human diseases, the expression and role of NTSR3/sortilin in NETs have not been elucidated. In this study, we investigated the expression and oncogenic effect of NTSR3/sortilin in NETs. Increased protein levels …

Novel Function Of Ceramide For Regulation Of Mitochondrial Atp Release In Astrocytes, Ji-Na Kong, Zhihui Zhu, Yutaka Itokazu, Guanghu Wang, Michael B. Dinkins, Liansheng Zhong, Hsuan-Pei Lin, Ahmed Elsherbini, Silvia Leanhart, Xue Jiang, Haiyan Qin, Wenbo Zhi, Stefka D. Spassieva, Erhard Bieberich

Physiology Faculty Publications

We reported that amyloid β peptide (Aβ₄₂) activated neutral SMase 2 (nSMase2), thereby increasing the concentration of the sphingolipid ceramide in astrocytes. Here, we show that Aβ₄₂ induced mitochondrial fragmentation in wild-type astrocytes, but not in nSMase2-deficient cells or astrocytes treated with fumonisin B1 (FB1), an inhibitor of ceramide synthases. Unexpectedly, ceramide depletion was concurrent with rapid movements of mitochondria, indicating an unknown function of ceramide for mitochondria. Using immunocytochemistry and super-resolution microscopy, we detected ceramide-enriched and mitochondria-associated membranes (CEMAMs) that were codistributed with microtubules. Interaction of ceramide with tubulin was confirmed by cross-linking to N-[9-(3-pent-4-ynyl-3-H-diazirine-3-yl)-nonanoyl]-D-erythro-sphingosine …

Genotype-Phenotype Study In Patients With Valosin-Containing Protein Mutations Associated With Multisystem Proteinopathy, Ebaa Al-Obeidi, Sejad Al-Tahan, Abhilasha Surampalli, Namita Goyal, Annabel K. Wang, Andreas Hermann, Molly Omizo, Charles D. Smith, Tahseen Mozaffar, Virginia Kimonis

Neurology Faculty Publications

Mutations in valosin‐containing protein (VCP), an ATPase involved in protein degradation and autophagy, cause VCP disease, a progressive autosomal dominant adult onset multisystem proteinopathy. The goal of this study is to examine if phenotypic differences in this disorder could be explained by the specific gene mutations. We therefore studied 231 individuals (118 males and 113 females) from 36 families carrying 15 different VCP mutations. We analyzed the correlation between the different mutations and prevalence, age of onset and severity of myopathy, Paget's disease of bone (PDB), and frontotemporal dementia (FTD), and other comorbidities. Myopathy, PDB and FTD was present in …