Gangliosides rescue neuronal cells from death after trophic factor deprivation

Autor: Anna Batistatou, Giovanna Ferrari, Lloyd A. Greene
Jazyk: angličtina
Rok vydání: 1993
Předmět:
Nerve Growth Factors/deficiency
Programmed cell death
Neurite
Neurons/*drug effects
Physiology
Macromolecular Substances
Protein Kinase C/metabolism
Nerve Tissue Proteins
G(M1) Ganglioside
Biology
PC12 Cells
G(M1) Ganglioside/pharmacology
chemistry.chemical_compound
Mice
Neurotrophic factors
Cell Death/drug effects
Gangliosides
medicine
Animals
Nerve Growth Factors
PC12 Cells/drug effects/metabolism
Protein Kinase C
Neurons
Ganglioside
Ganglia
Sympathetic
Cell Death
General Neuroscience
Apoptotic DNA fragmentation
Neurotoxicity
Ganglia
Sympathetic/cytology/drug effects
Articles
medicine.disease
Cell biology
Sialic acid
medicine.anatomical_structure
Blood
Biochemistry
chemistry
Cell culture
DNA Damage/drug effects
Nerve Tissue Proteins/*deficiency
DNA fragmentation
Neuron
Neurology (clinical)
Gangliosides/*pharmacology
DNA Damage
Popis: Serum-free cultures of PC 12 cells have been used as a model system for studying neuronal death occurring after neurotrophic factor deprivation. In this system, NGF rescues cells from death and prevents apoptotic DNA fragmentation. We report here that GM1 also promotes long- term survival of naive and NGF-pretreated PC 12 cells in serum-free medium and prevents internucleosomal cleavage of PC 12 cell DNA. In contrast to NGF, GM1 does not promote neurite outgrowth or somatic hypertrophy. The survival effects of GM1 are concentration dependent, with maximal activity at 30–50 microM. Optimal promotion of survival is obtained with multiple additions of GM1. Asialo-GM1 and sialic acid do not mimic these actions, indicating a requirement for the intact GM1 molecule. Prevention of serum-free PC 12 cell death is also obtained with di-, tri-, and tetrasialogangliosides. The ganglioside effects on survival and DNA fragmentation appear to be independent of macromolecular synthesis. GM1 is also effective under conditions in which cellular protein kinase C activity is downregulated by preexposure to high concentration of 12-O-tetradecanoylphorbol-13- acetate. Furthermore, GM1 promotes long-term survival of cultured rat sympathetic neurons after withdrawal of NGF. These findings complement prior observations that gangliosides protect cerebellar granule neurons from neurotoxicity caused by exposure to excitatory amino acids and extend the actions of gangliosides to rescue of neuronal cells deprived of neurotrophic factor support.
Databáze: OpenAIRE
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