Induction of the TRPM-2 gene in cells undergoing programmed death.

Abstract

RNA and protein products encoded by the testosterone-repressed prostate message-2 gene (TRPM-2) are induced to high levels, coordinate with the onset of cell death, in numerous rodent models of inducible tissue damage. These models include cell death initiated by hormonal stimuli (prostate regression), pressure insult (renal atrophy after ureteral obstruction), developmental stimuli (necrosis of interdigital tissue), and cytotoxic injury (chemotherapeutic regression of a tumor). Sequence analysis of cDNA encoding TRPM-2 revealed its close homology with a product referred to as SGP-2 or clusterin expressed constitutively by Sertoli cells; however, the immunologically related polypeptides expressed in regressing tissues differ in molecular mass from the forms secreted by the testis. Although the function(s) of the products encoded by the TRPM-2 gene remains unclear, their presence provides a remarkable and early indicator of programmed cell death in many types of mammalian cells.

Studies of specific gene induction during apoptosis of cell lines conditionally immortalized by SV40

“…This induction is more rapid than that of mdm-2, in agreement with the pro- Table 1 Expression of genes indentified by their diffential expression during apoptosis Gene(s) Induced in Expression in REtsAF Calmodulin, chondroitin sulfate Glucocorticoids induced thymocyte apoptosis [11,20] Not detected proteoglycan core protein RP8 Glutathione S-transferase Ybl Clusterin Ubiquitin Glucocorticoids or radiation induced thymocyte apoptosis [15] Prostate regression [32] and steroid induced lymphocyte apoptosis [21] Prostate regression and various other cell death process [17] Radiation-induced lymphocyte apoptosis [18] and insect muscles degeneration [19] [29], which suggest that, in some cells, p53 can mediate apoptosis by repressing survival genes. Recently, a reevaluation of the role of de novo protein synthesis in thymocyte apoptosis has also suggested that inhibitors of protein synthesis may delay apoptosis rather than prevent it [30], suggesting that some of the components of the apoptotic machinery are already present before apoptosis induction.…”

“…Clusterin, also called TRPM-2 and SGP-2, is an early indicator of programmed cell death [17]. The product of this gene is a sulfated glycoprotein the function of which remains unclear.…”

“…Three types of genes were studied: (1) genes identified during glucocorticoid-induced thymocyte apoptosis (RP-8) [11,15]; (2) during prostate regression and other cell-death processes (clusterin) [17]; and (3) during y irradiation-induced lymphocyte apoptosis [18] and insect muscle degeneration [19] (polyubiquitin). Fig.…”

“…Fig. 1 shows the example of RP-8 [15] and clusterin [17]. Clusterin is induced 10 h after the shift-up to the restrictive temperature (39.5°C) whereas RP-8 is constituvely expressed.…”

Resistance to Fas-mediated apoptosis: activation of Caspase 3 is regulated by cell cycle regulator p21WAF1 and IAP gene family ILP

“…Apoptotic cell death is accompanied by condensation and fragmentation of nuclei, loss of plasma membrane microvilli, condensation of cytoplasm, and fragmentation of chromosomal DNA into 180 bp oligomers and encountered in post embryonic and embryonic development (Wyllie et al, 1980;Buttyan et al, 1989). Apoptosis also plays the dominant role in various physiological cell death and disease states (Nagata and Golstein 1995;Suzuki et al, 1996a ± c;Nagata, 1997).…”