Biomedical subjects

S Kelić

Publications and source records attributed to S Kelić.

6 recordsLinked to original sources

PubMed2001

CD81 regulates neuron-induced astrocyte cell-cycle exit.

Astrocytes respond to contact with neurons by cell-cycle arrest and complex process formation. In our effort to discover the molecular mechanisms that underlie this phenomenon we have identified a known tetraspanin, CD81, as a critical component of astrocyte responses to neuronal differentiation signals. Here we show that CD81 is expressed on the surface of the astrocyte and that its expression level can be modulated by contact with neurons. Further, using three separate antibodies, 2F7, Eat1, and Eat2, which recognize unique epitopes in the extracellular domains of the CD81 protein, we show that there is a unique domain, recognized by Eat1, that is required for astrocyte cell-cycle withdrawal in response to neurons. This is likely due to conformational changes in the CD81 molecule, as inclusion of 2F7 actually augments neuron-induced astrocyte growth arrest. The critical nature of CD81 in normal astrocyte-neuron biology was confirmed by using mice in which CD81 had been deleted by homologous recombination. Astrocytes null at the CD81 locus were blind to the proliferative arrest encoded on the neuronal cell surface. Taken together, these data strongly suggest that CD81 is a critical regulator of neuron-induced astrocytic differentiation.

Animals↗

PubMed1997

Interferon-gamma alters nerve-induced redistribution of acetylcholine receptors in cultured rat skeletal muscle cells.

The influence of recombinant interferon-gamma (rIFN-gamma) on the development of acetylcholine receptor (AChR) aggregates in cocultures of rat embryonic muscle cells and spinal cord neurons was studied by counting the number of AChR aggregates in relation to cholinergic nerve fibers coming to the muscle fibers. rIFN-gamma caused no decrease in the number of cholinergic nerve fibers, but inhibited the increase in the number of AChR aggregates that occurs early during cocultivation and is an early sign in the development of neuromuscular junctions. rIFN-gamma stimulated release of nitric oxide, but no effects on aggregation of AChRs occurred after exposure to a nitric oxide synthase inhibitor, L-NG-monomethylarginine, or by the addition of nitroprusside, a generator of nitric oxide. No effect was seen on the number of AChR aggregates when the cultures were exposed to rIFN-gamma at later time points of cocultivation, when the increase in number of AChRs had already occurred. These studies indicate that the key immunoregulatory cytokine IFN-gamma can cause alterations in the early process of synapse formation and that these effects are independent of the nitric oxide release caused by the cytokine.

Animals↗

PubMed1995

Cholinergic-specific glycoconjugates.

Cholinergic nerve terminals utilize glycoconjugates in several ways, as surface markers and as structural components of the synaptic vesicles present within them. The surface markers have been discovered immunochemically: antibodies raised against them are able specifically to sensitize the cholinergic subpopulation of mammalian brain synaptosomes to complement-mediated lysis. One such group of antigens (Chol-1) have been identified as a novel series of minor gangliosides having in common a sialylated N-acetylgalactosamine residue. These gangliosides may constitute the major gangliosides at cholinergic terminals. A second surface antigen (Chol-2) is thought to be a protein with an epitope in common with a Torpedo electric organ ganglioside. Cholinergic synaptic vesicles are rich in a proteoglycan which appears to assist in the sequestration of acetylcholine within the vesicle and to stabilize the vesicle membrane during cycles of exocytosis and recovery. It may be the cholinergic equivalent of the chromogranins.

Antigens, Surface↗

PubMed1993

A novel cholinergic-specific antigen (Chol-2) in mammalian brain.

Three new antisera have been raised in sheep against cholinergic electromotor presynaptic plasma membranes prepared from the electric organs of the electric ray, Torpedo marmorata. They all recognized one or more cholinergic-specific antigens in the mammalian nervous system by the following criteria: they sensitized the cholinergic subpopulation of rat-brain synaptosomes--and only this subpopulation--to lysis by the complement system and, in an immunocytochemical study, selectively stained choline acetyltransferase-positive cholinergic neurons in the rat spinal cord. However, two of the three antisera failed to recognize Chol-1 alpha and -beta, two closely related minor gangliosides already identified as the cholinergic-specific antigens recognized by previous anti-Torpedo presynaptic plasma membrane antisera or indeed any other ganglioside and the third recognized only Chol-1 alpha. A further investigation of the antigen(s) recognized by the most antigenic of the new antisera indicated that it is proteinaceous in nature, but has epitopes in common with electric organ gangliosides.

Animals↗

PubMed1993

Interferon-gamma promotes proliferation of rat skeletal muscle cells in vitro and alters their AChR distribution.

Recombinant interferon-gamma (IFN-gamma) caused a dose-dependent increase in the proliferation of myoblasts in cultures of rat skeletal muscles as determined by bromodeoxyuridine incorporation. As a result of this proliferation the number of myotubes increased in the cultures, while the fusion index was unchanged. In myotubes exposed to IFN-gamma there was a change in the distribution of nicotinic acetylcholine receptors (nAChR) as detected by binding of FITC-conjugated alpha-bungarotoxin with a significant decrease in the number of linear aggregates and an increase in diffusely distributed receptors.

Acetylcholinesterase↗

PubMed1993

Mumps virus alters aggregation of acetylcholine receptors in cultured rat skeletal muscle cells.

Cultured myoblasts, but not myotubes, from rat skeletal muscles were infected with the RW strain of mumps virus. Such myoblasts then fused to form myotubes containing viral antigen. The infected myotubes showed a significant decrease in the number of dorsal, linear acetylcholine receptor (AChR) aggregates as determined by FITC-conjugated alfa-bungarotoxin. Infected myotubes co-cultivated with spinal cord cells showed no increase in the number of dorsal, linear AChR aggregates, compared to normal, uninfected myotubes. In addition, an increased proliferation of the myoblasts, which remained uninfected in the infected cultures, was noted. This may indicate a release of a growth stimulating factor from the virus containing cells. This study shows that mumps virus infection can lead to an altered receptor organization in a morphologically preserved cell.

Animals↗