Human gliomas and epileptic foci express high levels of a mRNA related to rat testicular sulfated glycoprotein 2, a purported marker of cell death.

Abstract

Clone pTB16 has been isolated by differential screening of a human glioma cDNA library. Northern blot analysis has shown that pTB16 expression is several times (>11-fold) higher in gliomas than in a primitive neuroectodermal tumor. This observation was supported by in situ hybridization and extended to nine other gliomas. Expression was virtually absent in adenocarcinoma cells metastasized to brain. Malignant gliomas showed stronger hybridization than benign gliomas, while blood capillaries did not show hybridization. pTB16 mRNA was also shown to be expressed in established glioma cell lines and at high levels in epileptic foci, indicating that expression of the gene may be limited to certain cell types and that its upregulation is not merely a consequence ofcellular proliferation. Nucleotide sequence analysis identified pTB16 as the human counterpart for rat testicular sulfated glycoprotein 2 (SGP-2), whose function in the reproductive system remains unknown. Although SGP-2 transcripts, and hence pTB16, were recently shown to be increased in neurodegenerative diseases such as scrapie in hamsters and Alzheimer disease in humans, our observations with brain tumors and epilepsy are suggestive of a role for pTB16 in neuropathologies in general and support the hypothesis of its involvement in tissue remodeling and cell death.

Up-regulation of clusterin (sulfated glycoprotein-2) in pancreatic islet cells upon streptozotocin injection to rats

“…One of the reasons for such susceptibility could be the absence of clusterin in these cells. We could hypothesize that clusterin might be involved in the biological processes of islet cell death and/or reorganization upon streptozotocin injection, since this protein has been shown to be involved in cell death (Buttyan et al 1989, Jenne & Tschopp 1989, Danik et al 1991, as well as in cell protection and tissue Figure 5 Clusterin immunoreactivity in the pancreatic islet of normal (a), and streptozotocin-treated rats at 1 (b), 3 (c), 6 (d), 12 (e) and 72 h (f) after treatment. As compared with normal rat (arrow in a), a considerable increase in clusterin immunoreactivity is seen as early as at 1 and 3 h after treatment (arrows in b and c), and lasted during the experimental period (arrows in b-f), even though some islet cells showed distinct degenerative changes with condensation of chromatin (arrowheads in d) and dissociation of cell-to-cell adhesion (asterisk in e) at 6 and 12 h after treatment.…”

Transient expression of clusterin (sulfated glycoprotein-2) during development of rat pancreas

“…Since then, it has been isolated and studied in various tissues. It has been reported as sulfated glycoprotein-2 from rat Sertoli cells (Griswold et al 1986), apolipoprotein-J, SP-40,40 or complement cytolysis inhibitor in human serum (Murphy et al 1988, Jenne & Tschopp 1989, de Silva et al 1990, testosterone repressed prostate message-2 in regressing rat ventral prostate (Leger et al 1987), glycoprotein 80 from canine kidney cells (Hartmann et al 1991), glycoprotein III from bovine adrenal chromaffin granules (Palmer & Christie 1990), T64 from Japanese quail neuroretinal cells (Michel et al 1989), pTB16 from human glioma (Danik et al 1991), and pADHC-9 in the brain from a patient with Alzheimer's disease (May et al 1989). As suggested from its widespread expression, it has been thought to be involved in numerous biological processes including spermatogenesis, immune regulation, lipid transport and apoptosis ( Jenne & Tschopp 1992, May & Finch 1992, Tenniswood et al 1992.…”

Clusterin Biogenesis Is Altered during Apoptosis in the Regressing Rat Ventral Prostate

“…Clusterin mRNA was first identified as an apoptosis-associated transcript when it was cloned from regressing rat ventral prostate and localized to dying epithelial cells by in situ hybridization (11,12). Increases in clusterin mRNA and protein levels have been consistently detected in apoptotic heart, brain, lung, liver, kidney, pancreas, and retinal tissue both in vivo and in vitro, establishing clusterin gene expression as a marker of apoptotic cell loss (8,10,11,(13)(14)(15)(16)(17)(18)(19)(20). However, clusterin protein has also been implicated in physiological processes that do not involve apoptosis, including the control of complement-mediated cell lysis, transport of ␤-amyloid precursor protein, shuttling of aberrant ␤-amyloid across the blood-brain barrier, lipid scavenging, membrane remodeling, cell aggregation, and protection from immune detection and tumor necrosis factor ␣-induced cell death (1,5,6,9,(21)(22)(23).…”