Prosaposin prevents programmed cell death of rat cerebellar granule neurons in culture. 1998

K Tsuboi, and M Hiraiwa, and J S O'Brien
Department of Neurosciences, University of California, San Diego, School of Medicine, La Jolla, CA 92093-0634, USA.

Prosaposin, the precursor of sphingolipid activator proteins (saposin A-D), has been reported to be a neurotrophic factor in vitro and in vivo. Prosaposin mRNA is transiently expressed at a high level in developing cerebellum during the period of granule cell proliferation and maturation, suggesting its significance during development of cerebellum. Here we investigated the neuroprotective effect of prosaposin on cerebellar granule neurons, exposing primary cerebellar granule cells to low K+ which induced programmed cell death. Prosaposin rescued mature cerebellar granule neurons in a bimodal manner. A similar neuroprotective effect was obtained using TX14(A), a 14-mer neurotrophic peptide derivative of prosaposin. An additive neuroprotective effect was observed between BDNF and TX14(A), but not between IGF-1 and TX14(A). Prosaposin rescued 60% of nifedipine sensitive cerebellar granule neurons as well as IGF-1, while BDNF did not. Furthermore, the neuroprotective action of prosaposin was inhibited by LY294002, a specific inhibitor of PI 3-kinase. These findings indicated that prosaposin had a trophic effect upon newborn cerebellar granule cells and that the neuroprotective action was similar to that of IGF-1 rather than BDNF. Prosaposin may play a role in cerebellar development during programmed cell death of cerebellar neurons.

UI MeSH Term Description Entries
D007334 Insulin-Like Growth Factor I A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor. IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009025 Morpholines Tetrahydro-1,4-Oxazines,Tetrahydro 1,4 Oxazines
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002531 Cerebellum The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills. Cerebella,Corpus Cerebelli,Parencephalon,Cerebellums,Parencephalons
D002867 Chromones 1,4-Benzopyrones,Chromone,1,4 Benzopyrones
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006023 Glycoproteins Conjugated protein-carbohydrate compounds including MUCINS; mucoid, and AMYLOID glycoproteins. C-Glycosylated Proteins,Glycosylated Protein,Glycosylated Proteins,N-Glycosylated Proteins,O-Glycosylated Proteins,Glycoprotein,Neoglycoproteins,Protein, Glycosylated,Proteins, C-Glycosylated,Proteins, Glycosylated,Proteins, N-Glycosylated,Proteins, O-Glycosylated

Related Publications

K Tsuboi, and M Hiraiwa, and J S O'Brien
February 2003, Journal of molecular neuroscience : MN,
K Tsuboi, and M Hiraiwa, and J S O'Brien
August 1995, Alcoholism, clinical and experimental research,
K Tsuboi, and M Hiraiwa, and J S O'Brien
January 2022, Journal of integrative neuroscience,
K Tsuboi, and M Hiraiwa, and J S O'Brien
August 1995, The Journal of pharmacology and experimental therapeutics,
K Tsuboi, and M Hiraiwa, and J S O'Brien
January 1997, Neurochemical research,
K Tsuboi, and M Hiraiwa, and J S O'Brien
April 2004, Bipolar disorders,
K Tsuboi, and M Hiraiwa, and J S O'Brien
February 2001, Neurochemistry international,
K Tsuboi, and M Hiraiwa, and J S O'Brien
February 2001, Neuroscience letters,
K Tsuboi, and M Hiraiwa, and J S O'Brien
November 2003, Brain research,
K Tsuboi, and M Hiraiwa, and J S O'Brien
August 2002, Neuroscience letters,
Copied contents to your clipboard!