i(3)so3-galactosylceramide and Neoplasms

Sulfatides (3-O-sulfogalactosylceramides, sulfated galactocerebrosides, SM4) are esters of sulfuric acid with galactosylceramides. These acidic glycosphingolipids, present at the external leaflet of the plasma membrane, are synthesized by a variety of mammalian cells. They are especially abundant in the myelin sheath of oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. Studies using cerebroside galactosyltransferase-deficient mice revealed that sulfatides are responsible for proper structure and functioning of myelin. Large amounts of sulfatides are also found in the kidney, gastrointestinal tract, islets of Langerhans, and membranes of erythrocytes, thrombocytes and granulocytes. They are ligands for numerous proteins, but in most cases the biological role of such interactions is poorly understood. A notable exception is their binding by P- and L-selectins. Platelet sulfatides are major ligands for P-selectin, and this interaction is critical for the formation of stable platelet aggregates. Sulfatides also bind to chemokines, and seem to play a role in regulation of cytokine expression in human lymphocytes and monocytes. Aberrant metabolism of sulfatides, could cause several important human diseases. In this article, we describe the changes in sulfatide expression associated with such nervous disorders as metachromatic leukodystrophy (MLD), Parkinson's disease and Alzheimer's disease, and several types of cancer, e.g. colon cancer, kidney cancer, and ovarian cancer. We also discuss the involvement of sulfatides in cancer progression, diabetes and autoimmune and immune disorders such as multiple sclerosis. This acidic glycosphingolipids seem to play an important role in pathogenesis of infectious diseases, serving as receptors for binding various bacteria and viruses.

Topics: Animals; Autoimmune Diseases; Blood Cells; Cell Membrane; Central Nervous System; Cytokines; Galactosylceramides; Gastrointestinal Tract; Humans; Islets of Langerhans; Kidney; Myelin Sheath; Neoplasms; Nervous System Diseases; Peripheral Nervous System; Selectins; Sulfoglycosphingolipids

Sulfatides are sphingolipids commonly found at the surface of most of eukaryotic cells. Sulfatides are not just structural components of the plasma membrane but also participate in a wide range of cellular processes including protein trafficking, cell adhesion and aggregation, axon-myelin interactions, neural plasticity, and immune responses, among others. The intriguing question is how can sulfatides trigger such cellular processes? Their dynamic presence and specific localization at plasma membrane sites may explain their multitasking role. Crystal and NMR structural studies have provided the basis for understanding the mechanism of binding by sulfatide-interacting proteins. These proteins generally exhibit a hydrophobic cavity that is responsible for the interaction with the sulfatide acyl chain, whereas the hydrophilic, negatively charged moiety can be found either buried in the hydrophobic cavity of the protein or exposed for additional intermolecular associations. Since sulfatides vary in their acyl chain composition, which are tissue-dependent, more emphasis on understanding acyl chain specificity by sulfatide-binding proteins is warranted. Importantly, changes in cellular sulfatide levels as well as circulating sulfatides in serum directly impact cardiovascular and cancer disease development and progress. Therefore, sulfatides might prove useful as novel biomarkers. The scope of this review is to overview cell functions and mechanisms of sulfatide recognition to better understand the role of these lipids in health and disease.

Topics: Animals; Autoimmunity; Cardiovascular Diseases; Carrier Proteins; Host-Pathogen Interactions; Humans; Immunity, Innate; Neoplasms; Platelet Adhesiveness; Platelet Aggregation; Sulfoglycosphingolipids

Topics: Animals; Galactosylceramides; Gangliosides; Glycolipids; Humans; Lipid Metabolism, Inborn Errors; Membrane Microdomains; Neoplasms; Sphingolipids; Sulfoglycosphingolipids

Sulfatide is associated with numerous health problems, affecting different parts of the human body, including the metastasis; however, the underlying mechanisms are yet to be fully elucidated. Sulfatide has been used to potential inhibitor for tumor cell metastasis. In the present study we synthesized oleic acid sulfated chitosan (OlcShCs). It shows structural similarity to sulfatide because of its functional groups (sulfate and fatty acyl chains). Chitosan has smart properties such as biocompatibility, biodegradability and non-toxicity. We have prepared oleic acid sulfated chitosan (OlcShCs) by chitosan modification to mimic sulfatide. Its structure was characterized by FT-IR, H-NMR, and thermogravimetric analysis. After characterization studies its antimicrobial, antifungal and cytotoxic properties were investigated. Oleic acid sulfated chitosan (OlcShCs) was tested for its anti-cancer potential against human cancer cell lines (HeLa (ATCC® CCL-2™)) for 24 h, 48 h and 72 h using the MTT assays. This new material which is soluble at physiological conditions, is a potential candidate for further metastasis inhibition investigations.

Topics: Antineoplastic Agents; Chitosan; HeLa Cells; Humans; Neoplasm Metastasis; Neoplasms; Oleic Acid; Sulfoglycosphingolipids

The identity of target antigen(s) in multiple sclerosis (MS) remains elusive despite much effort to identify it. We analyzed cerebrospinal fluid (CSF) from patients with MS, other neurological diseases (OND), other diseases (OD) and healthy controls for antibodies against purified sulfatide, a major glycosphingolipid of human myelin, by an enzyme-linked immunosorbent assay (ELISA) and a thin-layer chromatogram (TLC)-immunostaining technique. Elevated anti-sulfatide antibodies were significantly higher in MS patients as compared with the OND group (p<0.05) and all controls combined (P<0.025). Binding of high titer antibodies to sulfatide was confirmed with TLC-immunostaining. Anti-sulfatide antibodies were detected in all subtypes of MS although the frequency was higher in patients with secondary progressive MS (SPMS) than in patients with primary progressive (PPMS) and relapsing-remitting MS (RRMS). The data demonstrate a humoral response to sulfatide in the CSF of patients with MS.

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Central Nervous System Diseases; Chromatography, Thin Layer; Diabetes Mellitus; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lupus Vulgaris; Male; Middle Aged; Multiple Sclerosis; Myelin Sheath; Myocardial Infarction; Neoplasms; Protein Binding; Recurrence; Sulfoglycosphingolipids

It has long been controversial whether sulfatide stimulates blood coagulation or inhibits blood coagulation. In this paper, I demonstrated not only anticoagulant activity but also coagulant activity of sulfatide in vivo by using experimental animal models and presented the possibility that sulfatide may function contradictorily under physiological and/or pathological conditions. For instance, I presented possible involvement of sulfatide in thrombotic diseases associated with cancers.

Topics: Animals; Anticoagulants; Blood Coagulation; Coagulants; Factor XII; Humans; In Vitro Techniques; Mice; Neoplasms; Rats; Sulfoglycosphingolipids; Thrombosis

Topics: Animals; Cerebrosides; Hematologic Neoplasms; Mast Cells; Neoplasms; Rats; Sulfoglycosphingolipids