Background: Infection and inflammation of the reproductive tract are significant causes of male factor infertility. Ascending infections caused by sexually transmitted bacteria or urinary tract pathogens represent the most frequent aetiology of epididymo-orchitis, but viral, haematogenous dissemination is also a contributory factor. Limitations in adequate diagnosis and therapy reflect an obvious need for further understanding of human epididymal and testicular immunopathologies and their contribution to infertility.
View Article and Find Full Text PDFThe vacuolar ATPase (V-ATPase) proton pump sustains cellular pH homeostasis, and its inhibition triggers numerous stress responses. However, the cellular mechanisms involved remain largely elusive in cancer cells. We studied V-ATPase in the prostate cancer (PCa) cell line PC-3, which has characteristics of highly metastatic PCa.
View Article and Find Full Text PDFExperimental autoimmune epididymo-orchitis (EAEO) is a model of chronic inflammation, induced by immunisation with testicular antigens, which reproduces the pathology of some types of human infertility. Activins A and B regulate spermatogenesis and steroidogenesis, but are also pro-inflammatory, pro-fibrotic cytokines. Expression of the activins and their endogenous antagonists, inhibin and follistatin, was examined in murine EAEO.
View Article and Find Full Text PDFUrinary tract infections caused by uropathogenic Escherichia coli (UPEC) pathovars belong to the most frequent infections in humans. In men, pathogens can also spread to the genital tract via the continuous ductal system, eliciting bacterial prostatitis and/or epididymo-orchitis. Antibiotic treatment usually clears pathogens in acute epididymitis; however, the fertility of patients can be permanently impaired.
View Article and Find Full Text PDFDespite antibiotic treatment, up to 40% of patients have impaired fertility after epididymitis due to serovars of Escherichia coli, a frequent pathogen. The reasons for infertility are unclear, but it may result from epididymal duct obstruction. To determine whether E.
View Article and Find Full Text PDFAcute epididymitis represents a common medical condition in the urological outpatient clinic. Mostly, epididymitis is caused by bacterial ascent through the urogenital tract, with pathogens originating either from sexually transmitted diseases or urinary tract infections. Although conservative antimicrobial therapy is possible in the majority of patients and is usually sufficient to eradicate the pathogen, studies have shown persistent oligozoospermia and azoospermia in up to 40% of these patients.
View Article and Find Full Text PDFFibroblasts from a patient with postural orthostatic tachycardia syndrome (POTS), who presented with low plasma choline and betaine, were studied to determine the metabolic characteristics of the choline deficiency. Choline is required for the synthesis of the phospholipid phosphatidylcholine (PC) and for betaine, an important osmoregulator. Here, choline transport, lipid homeostasis, and mitochondria function were analyzed in skin fibroblasts from POTS and compared with control cells.
View Article and Find Full Text PDFThe pathomechanism of peroxisomal biogenesis disorders (PBDs), a group of inherited autosomal recessive diseases with mutations of peroxin (PEX) genes, is not yet fully understood. Therefore, several knockout models, e.g.
View Article and Find Full Text PDFInfectious epididymitis in men, a frequent entity in urological outpatient settings, is commonly caused by bacteria originating from the anal region ascending the genitourinary tract. One of the most prevalent pathogens associated with epididymitis is Escherichia coli. In our previous study, we showed that semen quality is compromised in men following epididymitis associated with specific E.
View Article and Find Full Text PDFVacuolar ATPases (V-ATPases) comprise specialized and ubiquitously distributed pumps that acidify intracellular compartments and energize membranes. To gain new insights into the roles of V-ATPases in prostate cancer (PCa), we studied the effects of inhibiting V-ATPase pumps in androgen-dependent (LNCaP) and androgen-independent (C4-2B) cells of a human PCa progression model. Treatment with nanomolar concentrations of the V-ATPase inhibitors bafilomycin A or concanamycin A reduced the in vitro invasion in both cell types by 80%, regardless that V-ATPase was prominent at the plasma membrane of C4-2B cells and only traces were detected in the low-metastatic LNCaP parental cells.
View Article and Find Full Text PDFCholine is a zwitter ion that is positively charged at certain pH, which necessitates transport systems to allow this amine to cross the phospholipid bilayer of cellular membranes. The solute carrier 44A1 (SLC44A1), also referred to as choline transporter-like protein 1 (CTL1), is a recently discovered choline transporter with an intermediate affinity for choline; this transport is Na(+)-independent and sensitive to inhibition by the drug hemicholinium-3. We highlight in this review the discovery and characterization of SLC44A1, describe its expression patterns and subcellular localization, and summarize evidence for the role of this choline transporter in the central nervous system.
View Article and Find Full Text PDFConsumption of choline-rich foods is essential to ensure membrane integrity, neurotransmission and genomic methylation pathways. Insufficient dietary choline supply can cause choline deficiency (CD) which manifests in the development of non-alcoholic fatty liver disease. There is very limited information regarding the effect of CD on non-hepatic tissues such as muscle.
View Article and Find Full Text PDFThe expression of the CTP: phosphoethanolamine cytidylyltransferase gene Pcyt2 is significantly up-regulated during C2C12 muscle cell differentiation, which was demonstrated by elevated Pcyt2 protein ( approximately 2.3-fold), mRNA ( approximately 2.6-fold) and promoter activity ( approximately 2-fold) in myotubes relative to myoblasts.
View Article and Find Full Text PDFCholine oxidation to betaine takes place in the mitochondria; however, a protein regulating mitochondrial choline transport was never identified. The purpose of this study was to analyze subcellular localization of the solute carrier 44A1 (SLC44A1), a plasma membrane choline transporter sensitive to inhibition by hemicholinium-3. We generated N- and C-terminal-SLC44A1-specific antibodies and analyzed localization of endogenous and overexpressed SLC44A1 in C2C12 mouse muscle cells, MCF7 human breast cancer cells, and mouse tissues using confocal microscopy, differential centrifugation, and Western blotting.
View Article and Find Full Text PDFThe CDP-ethanolamine branch of the Kennedy pathway is the major route for the formation of ethanolamine-derived phospholipids, including diacyl phosphatidylethanolamine and alkenylacyl phosphatidylethanolamine derivatives, known as plasmalogens. Ethanolamine phospholipids are essential structural components of the cell membranes and play regulatory roles in cell division, cell signaling, activation, autophagy, and phagocytosis. The physiological importance of plasmalogens has not been not fully elucidated, although they are known for their antioxidant properties and deficiencies in a number of inherited peroxisomal disorders.
View Article and Find Full Text PDFLipid rafts are sphingolipid- and cholesterol-rich domains of the plasma membrane which contain a variety of signalling and transport proteins. Different subtypes of lipid rafts can be distinguished according to their protein and lipid composition. Caveolae are types of rafts that are rich in proteins of the caveolin family (caveolin-1, -2 and -3) which present a distinct signalling platform.
View Article and Find Full Text PDFCholine is an essential nutrient for all cells because it plays a role in the synthesis of the membrane phospholipid components of the cell membranes, as a methyl-group donor in methionine metabolism as well as in the synthesis of the neurotransmitter acetylcholine. Choline deficiency affects the expression of genes involved in cell proliferation, differentiation, and apoptosis, and it has been associated with liver dysfunction and cancer. Abnormal choline transport and metabolism have been implicated in a number of neurodegenerative disorders such as Alzheimer's and Parkinson's disease.
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