A5024995579- Drug Transport and Resistance Mechanisms
- Pharmacological Effects and Toxicity Studies
- Hepatitis B Virus Studies
- Estrogen and related hormone effects
- Metabolism and Genetic Disorders
- Ion Transport and Channel Regulation
- Pharmacogenetics and Drug Metabolism
- Liver Disease Diagnosis and Treatment
- Amino Acid Enzymes and Metabolism
- Pediatric Hepatobiliary Diseases and Treatments
- Hormonal and reproductive studies
- Hepatitis C virus research
- Reproductive System and Pregnancy
- Sperm and Testicular Function
- Antibiotics Pharmacokinetics and Efficacy
- Epigenetics and DNA Methylation
- Ion channel regulation and function
- Urinary Bladder and Prostate Research
- Anesthesia and Pain Management
- Hepatitis Viruses Studies and Epidemiology
- Cannabis and Cannabinoid Research
- Helminth infection and control
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Sexual Differentiation and Disorders
- Epilepsy research and treatment
Justus-Liebig-Universität Gießen
2016-2025
Institute of Pharmacology
2024
Tufts Medical Center
1990
Klinikum Darmstadt
1988
Freie Universität Berlin
1976
Abstract Cellular entry of the hepatitis B and D viruses (HBV/HDV) requires binding viral surface polypeptide preS1 to hepatobiliary transporter Na + -taurocholate co-transporting (NTCP). This interaction can be blocked by bulevirtide (BLV, formerly Myrcludex B), a derivative approved drug for treating HDV infection. Here, elucidate basis this inhibitory function, we determined cryo-EM structure BLV-bound human NTCP. BLV forms two domains, plug lodged in bile salt transport tunnel NTCP...
Significance Hepatitis B virus (HBV) is the prototype hepadnavirus; 40% of humans have current or past infection. In a global investigation viral diversity in bats, we discovered three unique hepadnavirus species. The relatedness these viruses to HBV suggests that bats might constitute ancestral sources primate hepadnaviruses. Infection patterns resembled human infection with HBV. After resurrection from bat tissues, pseudotyped carrying surface proteins one could infect liver cells....
The human liver bile acid transporter Na(+)/taurocholate cotransporting polypeptide (NTCP) has recently been identified as liver-specific receptor for infection of hepatitis B virus (HBV), which attaches via the myristoylated preS1 (myr-preS1) peptide domain its large surface protein to NTCP. Since binding myr-preS1 NTCP is an initiating step HBV infection, we investigated if this process interferes with physiological transport function NTCP.HBV binding, and assays were performed primary...
Highlights•A divergent HBV species termed CMHBV was discovered in Brazilian capuchin monkeys.•CMHBV and the related WMHBV use same receptor as to infect human cells.•CMHBV may cause chronic hepatitis B, potentially enabling new animal models.•Primates have been carrying HBV-related viruses for millions of years.•New World genotypes were likely introduced during peopling Americas.Graphical abstractAbstractBackground & AimsAll known B virus (HBV) occur humans hominoid Old non-human primates...
Fluorescence in situ hybridization (FISH) analysis has shown that human embryos display a high level of chromosomal mosaicism at all preimplantation stages. The aim this study was to investigate the mechanisms involved by use two probes for each three autosomes different loci and determine true aneuploid excluding FISH artefacts.Embryos were cultured types medium: group I standard cleavage medium up day 5 II from 3 blastocyst medium. Three rounds performed. In round 1, used 1pTel, 11qTel...
We have cloned human sodium-dependent organic anion transporter (SOAT) cDNA, which consists of 1502 bp and encodes a 377-amino acid protein. SOAT shows 42% sequence identity to the ileal apical bile ASBT 33% hepatic Na(+)/taurocholate-cotransporting polypeptide NTCP. Immunoprecipitation SOAT-FLAG-tagged protein revealed glycosylated form at 46 kDa that decreased 42 after PNGase F treatment. exhibits seven-transmembrane domain topology with an outside-to-inside orientation N-terminal...
Within the combined DFG research project "Sulfated Steroids in Reproduction" an analytical method was needed for determining sulfated and unconjugated steroids with highest specificity out of different biological matrices such as aqueous solution, cell lysate serum. With regard to this challenge, LC-MS-MS presents technique choice because it permits (1) analysis intact steroid conjugate, (2) allows simultaneous determination multiple analytes (profiling, targeted metabolomics approach) (3)...
Sulfated steroid hormones are commonly considered to be biologically inactive metabolites, but may reactivated by the sulfatase into active free steroids, thereby having regulatory function via nuclear androgen and estrogen receptors which widespread in testis. However, a prerequisite for this mode of action would carrier-mediated import hydrophilic sulfate molecules specific target cells reproductive tissues such as In present study we detected predominant expression Sodium-dependent...
Peripheral tissues such as skin and adipose tissue play a crucial role in the intracrine formation of sex steroid hormones, complementing endocrine paracrine systems. These mechanisms involve conversion dehydroepiandrosterone (DHEA) its sulfated form—DHEAS—into potent androgenic estrogenic hormones. In vitro studies using tissue-specific cell lines are essential for unraveling complex synthesis these This study examined DHEA, androstenedione (A4), testosterone (T), dihydrotestosterone (DHT),...
P‐glycoprotein, which is encoded by the multi‐drug resistance gene (MDR1), highly restricts entry of ivermectin into brain an ATP‐driven efflux mechanism at blood–brain barrier. In dogs with a homozygous MDR1 mutation though, accumulates in and provokes severe signs neurotoxicosis even death. contrast to ivermectin, selamectin safer treatment mutant dogs, suggesting that transported differently P‐glycoprotein across To test this, we applied mdr1‐deficient mdr1a,b −/− knockout mice wild‐type...
The NTCP (Na⁺-taurocholate co-transporting protein)/SLC10A [solute carrier family 10 (Nav/bile acid co-transporter family)] 1 is tightly controlled to ensure hepatic bile salt uptake while preventing toxic accumulation. Many transport proteins require oligomerization for their activity and regulation. This not yet established transporters. present study was conducted elucidate the oligomeric state of NTCP. Chemical cross-linking revealed presence dimers in rat liver membranes U2OS cells...
The hepatic Na+/taurocholate co-transporting polypeptide (NTCP in man, Ntcp animals) is the high-affinity receptor for hepatitis B (HBV) and D (HDV) viruses. Species barriers human HBV/HDV within order Primates were previously attributed to sequence variations that disable virus-receptor interaction. However, only a limited number of primate Ntcps have been analysed so far. In present study, total 11 from apes, Old New World monkeys cloned expressed vitro characterise their interaction with...
Abstract Current treatment options against hepatitis B and D virus (HBV/HDV) infections have only limited curative effects. Identification of Na + /taurocholate co-transporting polypeptide (NTCP) as the high-affinity hepatic receptor for both viruses in 2012 enables target-based development HBV/HDV cell-entry inhibitors. Many studies already identified appropriate NTCP However, most them interfere with NTCP’s physiological function a bile acid transporter. To overcome this drawback, present...
The Na+/taurocholate co-transporting polypeptide (NTCP, gene symbol SLC10A1) is both a physiological bile acid transporter and the high-affinity hepatic receptor for hepatitis B D viruses (HBV/HDV). Virus entry via endocytosis of virus/NTCP complex involves co-factors, but this process not fully understood. As part innate immunity, interferon-induced transmembrane proteins (IFITM) 1-3 have been characterized as virus entry-restricting factors many viruses. present study identified IFITM3...
MDR1 (ABCB1) P-glycoprotein exerts a protective function in the blood-brain barrier thereby limiting entry of many drugs and other xenobiotics to central nervous system. A nonsense mutation has been described for Collies related dog breeds which abolishes this is associated with increased susceptibility neurotoxic side effects several including ivermectin, moxidectin loperamide. In order evaluate occurrence frequency nt230 (del4) Germany, we screened 1500 dogs. Frequency homozygous mutated...
Biotin-thiamine-responsive basal ganglia disease (BTBGD) is a potentially treatable disorder caused by mutations in the SLC19A3 gene, encoding human thiamine transporter 2. Manifestation of BTBGD as acute encephalopathy triggered febrile infection has been frequently reported, but underlying mechanisms are not clear. We investigated family with two brothers being compound heterozygous for p.W94R and p.Q393*fs. Post-mortem analysis brain one brother showed mixture acute, subacute chronic...
Candida albicans RCH1 (regulator of Ca(2+) homoeostasis 1) encodes a protein ten TM (transmembrane) domains, homologous with human SLC10A7 (solute carrier family 10 member 7), and Rch1p localizes in the plasma membrane. Deletion confers hypersensitivity to high concentrations extracellular tolerance azoles Li(+), which phenocopies deletion CaPMC1 (C. PMC1) encoding vacuolar pump. Additive mutation, lack alone shows an increase sensitivity, uptake cytosolic level. The is abolished by...