Disease relevance of Psap

• Prosaposin mRNA was detected in the rat RPE cell monolayer and in ganglion cells 14, 21, and 45 days after birth [1].
• The prosaposin effect was also inhibited by pertussis toxin, indicating that the prosaposin receptor is a G-protein-coupled receptor [2].
• The lack of ganglioside GM1 accumulation in patients suffering from either prosaposin or GM2 activator protein deficiency has led to the hypothesis that SAPs are not needed for the hydrolysis of the ganglioside GM1 in vivo [3].
• An 18-mer peptide fragment of prosaposin ameliorates place navigation disability, cortical infarction, and retrograde thalamic degeneration in rats with focal cerebral ischemia [4].
• In the present study, we show that prosaposin mRNA is significantly (p < 0.05) elevated in the peripheral nerve of streptozotocin-diabetic rats, a model of insulin-deficient diabetes in which nerve injury arises from the metabolic trauma of hyperglycemia and its consequences [5].

Psychiatry related information on Psap

• Administration of prosaposin ameliorates spatial learning disturbance and reduces cavity formation following stab wounds in rat brain [6].

High impact information on Psap

• The SGP-1 expresses both alpha6beta1 integrin and cytoplasmic laminin [7].
• However, when SGP-1 cells were transplanted into the liver via the portal vein, these cells were integrated into hepatic trabecula and produced albumin [7].
• We report that prosaposin treatment induced extracellular signal-regulated kinases (ERKs) and sphingosine kinase activity, increased DNA synthesis, and prevented cell apoptosis [2].
• Prosaposin rescued PC12 cells from apoptosis induced by staurosporine or ceramide [2].
• Prosaposin, the precursor of saposins A, B, C, and D, was recently reported to be a neurotrophic factor in vivo and in vitro [8].

Chemical compound and disease context of Psap

• Recently, the trophic activity of prosaposin on human neuroblastoma cells has been shown to reside in the NH2-terminal hydrophilic sequence (LIDNNRTEEILY) of the human saposin C [9].
• Prosaposin and D5 inhibited K+-stimulated synaptosomal 45Ca2+ uptake similar to omega-conotoxin MVIIC, demonstrating that both effectors modulated voltage-dependent calcium channels (VDCC); inhibition was largely abolished by pretreatment with pertussis toxin before D5 treatment [10].

Biological context of Psap

• Prosaposin gene expression in normal and dystrophic RCS rat retina [1].
• The increase in the amount of prosaposin mRNA in normal retinas coincided with the maturation of photoreceptor cells and the beginning of the phagocytosis process [1].
• The presence of internal sequence similarity suggests that three additional binding sites may occur in SGP-1 [11].
• The lysosomal form of SGP-1 plays a role in the hydrolysis of glycolipids and sphingomyelin [12].
• Expression and tissue distribution of rat sulfated glycoprotein-1 (prosaposin) [12].

Anatomical context of Psap

• Sulfated glycoprotein 1 (SGP-1) is one of the abundant proteins secreted by rat Sertoli cells [11].
• In addition, the RCS rdy- RPE cells, characterized by the abrogation of the ingestion phase of the photoreceptor outer segments, are deficient in prosaposin expression [1].
• Pulse-chase labeling shows that SGP-1 is synthesized as a cotranslationally glycosylated 67-kilodalton (kDa) precursor which is posttranslationally modified to a 70-kDa form before secretion to the extracellular space [11].
• The site of SGP-1 synthesis in testis was localized to Sertoli cells by immunofluorescence and in situ hybridization [11].
• Sequence comparisons suggest that SGP-1 is the precursor to sulfatide/GM1 activator; however, the secretion of the protein from Sertoli cells is distinct from the proteolytic processing and lysosomal compartmentalization which have been described for human fibroblasts [11].

Associations of Psap with chemical compounds

• To investigate the role of glucocorticoids in the stress-induced decrease in hippocampal prosaposin, adrenalectomized and corticosterone-treated rats were studied [13].
• Consensus sequences constructed for the b-type repeats were used to search the data base for homologous sequences, and the search has revealed that prosaposin and sulfated glycoprotein 1 show a remarkable homology with these repeats [14].
• These findings offer a possible explanation for the observation that no storage of the ganglioside GM1 has been observed in patients with either isolated prosaposin or isolated GM2 activator deficiency [3].
• Recently, TX14(A), a prosaposin-derived neurotrophic peptide, was shown to prevent both large and small fiber deficits in streptozotocin diabetes [15].
• TX14(A), a prosaposin-derived peptide, reverses established nerve disorders in streptozotocin-diabetic rats and prevents them in galactose-fed rats [15].

Other interactions of Psap

• 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 [16].
• Sphingosine kinase activity was increased by prosaposin treatment [2].
• This group includes SGP-1 and SGP-2 which are the major sertoli cell products in rats and which have been well-characterized biochemically.(ABSTRACT TRUNCATED AT 400 WORDS)[17]
• Histone-associated DNA fragmentation enzyme-linked immunosorbent assay, showed a 10- and 14-fold increase in apoptosis after 4 and 24 hr in low serum medium, respectively, that was reduced by prosaposin, TX14(A), or IGF-I [18].
• Thus, it appears that this unique lysosomal form of SGP-1 reached the Sertoli cell phagosomes and that their derived polypeptides, the saposins, must play a role in the hydrolysis of membrane glycolipids found in phagocytosed residual bodies [19].

Analytical, diagnostic and therapeutic context of Psap

• Northern blots show similar levels of expression for the 2.6-kilobase SGP-1 mRNA in all tissues examined [11].
• Sequence analysis showed a near-identical nucleotide and amino acid similarity to a previous rat SGP-1 cDNA [12].
• The SGP-1 cDNA construct was generated by amplifying a rat testicular Zap cDNA library by PCR (polymerase chain reaction) with two synthetic oligonucleotide primers [12].
• After sciatic nerve transection, Western blot analysis demonstrated the presence of intact prosaposin in tubular fluid in a silicon chamber into which the proximal and distal nerve stumps were sutured [20].
• Consistent with this finding, prosaposin-like immunoreactive neurons and fibers as revealed by immunohistochemistry were observed frequently in subcortical regions [21].

References