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PubMed2006

Differential regulation of clusterin and its isoforms by androgens in prostate cells.

Clusterin mRNA levels were shown to increase dramatically in rat ventral prostate following castration, and clusterin was therefore originally thought to be repressed by androgens. It was later discovered that the increased clusterin levels are most likely due to castration-induced apoptosis of the prostatic epithelium rather than direct action of the androgen receptor (AR). In the studies presented here, LNCaP cells in culture and rat prostate organ culture were treated with androgens. Clusterin mRNA and protein are shown to increase with androgen treatment in a time- and dose-dependent manner. This induction of clusterin requires AR and can be inhibited by casodex, an AR antagonist. We have found that the first intron of the clusterin gene contains putative androgen response elements. The intronic region is shown to be bound by AR in chromatin immunoprecipitation assays and is transactivated by AR in reporter assays. Two isoforms of clusterin result from alternate transcriptional start sites. Both isoforms are cytoprotective; however, Isoform 1 has the capacity to produce a splice variant that is apoptotic. Real time PCR was used to determine the response of the two isoforms to androgens. Intriguingly, these results illustrated that Isoform 2 was up-regulated, whereas Isoform 1 was down-regulated by androgens. Isoform 2 was also increased as the LNCaP xenograft tumor progressed to androgen-independence, whereas Isoform 1 was unaltered. This androgen regulation of clusterin may underline the cytoprotective role of androgens in normal prostate physiology as well as play an antiapoptotic role in prostate cancer progression.

Alternative Splicing↗
PubMed2001

Acquisition of resistance to Fas-mediated apoptosis by overexpression of clusterin in human renal-cell carcinoma cells.

Recent studies have shown the antiapoptotic activity of clusterin against a wide variety of stimuli; however, the functional role of clusterin in Fas-mediated apoptosis has not been well characterized. We transfected the clusterin cDNA into human renal-cell carcinoma (RCC) ACHN cells that scarcely express clusterin protein in order to examine whether overexpression of clusterin inhibits the Fas-mediated signal pathway for apoptotic cell death. No significant difference was observed in the in vitro cell growth rates between the clusterin-transfected cell line (ACHN/CL) and the vector-only-transfected control cell line (ACHN/C), whereas the colony-forming efficiency in soft agar of ACHN/CL was significantly higher than that of ACHAN/C. The anti-Fas monoclonal antibody CH11 induced apoptosis in ACHAN/C cells in a dose-dependent manner; however, the growth-inhibitory effect of CH11 on ACHN/CL cells was markedly suppressed, with corresponding increases in p53 expression and decrease in the fraction of cells in the sub-G(1) phase of the cell cycle. Furthermore, the cytotoxic effect of CH11 on ACHN/CL cells was augmented by treatment with interferon-gamma, but a corresponding effect on ACHN/C cells was not observed. These findings suggest that overexpression of clusterin may contribute to a phenotype resistant to Fas-mediated apoptosis, and that if interferon-gamma treatment is added according to the clusterin expression level, Fas-mediated therapy could be a novel approach to RCC.

Adult↗
PubMed1996

Modulation of clusterin gene expression in the rat mammary gland during pregnancy, lactation, and involution.

The mammary gland provides an excellent system for investigating factors involved in the regulation of epithelial growth, differentiation, morphogenesis, and involution. We have recently demonstrated that clusterin gene expression is associated with epithelial differentiation and morphogenesis during murine embryogenesis. In the present study, we have analyzed expression of clusterin in the rat mammary gland with particular emphasis on the periods of pregnancy and lactation. By Northern blot analysis we show that clusterin mRNA is present in virgin rat mammary glands, that it is increased during pregnancy and strongly down-regulated during lactation, and that mRNA levels return progressively to those found in virgin rats during the course of involution. Total protein levels, as assessed by Western blot analysis, were also seen to decrease during lactation. In situ hybridization showed that strong expression of clusterin was localized to epithelial cells of developing lactiferous ducts and alveoli during pregnancy, and confirmed that epithelial clusterin expression is down-regulated during lactation. This down-regulation was reproducibly observed in mothers to which pups were returned after 2 days of weaning, suggesting that maternal mammary clusterin production is under hormonal control. These results show that clusterin gene expression is highest in alveolar and tubular epithelial cells during pregnancy and lowest during lactation, when the protein synthetic machinery of differentiated alveolar epithelial cells is devoted to milk production. This suggests that clusterin may be involved not only in mammary gland involution but also in the regulation of tubuloalveolar morphogenesis and alveolar epithelial cell differentiation in the adult rat mammary gland.

Animals↗
PubMed2002

Clusterin expression in malignant lymphomas: a survey of 266 cases.

Clusterin expression has been reported to be characteristic of systemic anaplastic large cell lymphoma and usually negative in cutaneous anaplastic large cell lymphoma as well as other lymphoma types. We surveyed clusterin expression using immunohistochemical methods in 266 cases of non-Hodgkin's lymphoma and Hodgkin's disease to further assess the diagnostic utility of this marker. Clusterin immunostaining was observed in 40 of 49 (82%) systemic anaplastic large cell lymphomas and 12 of 29 (41%) cutaneous anaplastic large cell lymphomas. Clusterin also was expressed in 5 of 43 (12%) diffuse large B-cell lymphomas (4 of 5 CD30+), 1 of 14 (7%) peripheral T-cell lymphomas, 1 of 32 (3%) cases of nodular sclerosis Hodgkin's disease, and 1 case of mycosis fungoides in large cell transformation. Clusterin was negative in all other neoplasms assessed including follicular lymphoma of all grades (n = 24), mantle cell lymphoma (n = 13), marginal zone B-cell lymphoma (n = 12), precursor T-cell or B-cell lymphoblastic leukemia/lymphoma (n = 10), mixed cellularity Hodgkin's disease (n = 8), chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 7), Burkitt lymphoma (n = 7), mycosis fungoides (n = 4), nodular lymphocyte predominant Hodgkin's disease (n = 3), lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (n = 2), and plasmacytoma (n = 2). We conclude that clusterin is a marker of anaplastic large cell lymphoma and that addition of clusterin to antibody panels designed to distinguish systemic anaplastic large cell lymphoma from classical Hodgkin's disease is useful. However, clusterin is also positive in a substantial subset of cutaneous anaplastic large cell lymphomas, a smaller subset of diffuse large B-cell lymphomas, and rarely in cases of peripheral T-cell lymphoma and nodular sclerosis Hodgkin's disease.

Anaplastic Lymphoma Kinase↗
PubMed1992

Membrane attack complex (MAC) deposits in skin are not always accompanied by S-protein and clusterin.

Clusterin and S-protein bind to the membrane attack complex of complement (MAC) rendering it cytolytically inactive. Tissue necrosis as produced by pulsed tunable dye laser therapy (PTDL), and immune complex-related diseases such as lupus erythematosus, are accompanied by local accumulation of MAC. However, the mechanisms responsible for this accumulation might differ, and lead to deposition of MAC in different forms (cytolytically active or inactive). Biopsy specimens of lesional (22) and non-lesional (10) skin from 27 patients with a positive lupus band test (LBT) were studied using monoclonal antibodies against clusterin, S-protein, and MAC by immunofluorescence and immunoperoxidase. Identical studies were performed in normal and angiomatous skin specimens from three normal individuals before and after laser irradiation. MAC was present in 30 of 32 positive LBT skin biopsies. MAC was not only present in lesional (21 of 22) but also in non-lesional skin (nine of 10), although the intensity of staining appeared to be lower in the latter. Clusterin and S-protein co-localized with MAC, respectively, in 20 and 12 specimens, and were not found in the absence of MAC. In addition S-protein deposits were seen only in biopsies positive for clusterin. Deposits of clusterin and S-protein did not correlate with the presence or absence of lesions. After irradiation with PTDL, the immediate complement activation was accompanied by MAC deposits that were granular and clearly located on vascular endothelial cells. Clusterin and S-protein were not present on these cells. In summary, clusterin localizes with MAC along the skin dermal-epidermal junction in patients with a positive LBT, suggesting that it has a similar and possibly more important role than S-protein in regulating immune complex-mediated MAC formation. By contrast, clusterin and S-protein are not involved at the time of MAC formation in cells undergoing necrosis after PTDL therapy.

Biopsy↗
PubMed2001

Binding of human clusterin by Staphylococcus epidermidis.

To hypothesise that Staphylococcus epidermidis may possess clusterin receptor(s), bacterial binding of human clusterin was determined. In a fluid phase, the binding was markedly influenced by culture medium and three out of 12 S. epidermidis strains grown on ISO-sensitest agar expressed clusterin-binding ability. S. epidermidis J9P, selected for further study, showed saturable binding of iodine-labelled clusterin, and the binding was only inhibited by unlabelled clusterin. The binding was sensitive to protease treatment. Scatchard plot indicated one single class of binding sites (K(d)=104.2 nM). None of the S. epidermidis strains bound immobilised clusterin. These data imply that ligand-receptor interaction exists between S. epidermidis and clusterin in fluid phase, but the domain(s) recognised by bacteria may have been occluded when clusterin was adsorbed on a surface.

Clusterin↗
PubMed2004

The retinoid antagonist MX781 induces clusterin expression in prostate cancer cells via heat shock factor-1 and activator protein-1 transcription factors.

Retinoids mediate numerous biological responses through the transcriptional activation of nuclear retinoid receptors. Due to their antiproliferative activity, retinoids have shown promise as anticancer agents. Synthetic analogs have been described that selectively activate one subset of the retinoid receptors or inhibit their transcriptional activity. Some of these compounds exhibit strong anticancer activity, which is associated with their ability to induce apoptosis. Here we describe that the retinoid antagonist MX781 causes a substantial increase of clusterin mRNA and protein levels in prostate carcinoma cells. In contrast, retinoic acid and other synthetic agonists and antagonists show no effect on clusterin mRNA/protein levels. Induction of clusterin mRNA is associated with transcriptional activation of the clusterin promoter, which requires the proximal -218-bp region containing binding sites for heat shock factor (HSF)-1, activator protein (AP)-2, and AP-1 transcription factors. MX781 slightly induces AP-1 DNA binding activity, and mutation of the AP-1 site differentially affects the activation of the clusterin promoter in a cell type-specific manner. In contrast, a robust increase of HSF-1 DNA binding activity is observed in all cancer cell lines examined, and mutation of the heat shock element site in the clusterin promoter completely abolishes MX781-induced transcriptional activation in PC3 and DU145 cells. Other agonist retinoid-related molecules also induce AP-1 activity, but not HSF-1, and elicit no effect on clusterin expression levels. These data point to HSF-1 as an important factor regulating clusterin expression in response to MX781, although AP-1 activity may also participate in a cell type-specific manner.

Apoptosis↗
PubMed1994

Human clusterin gene expression is confined to surviving cells during in vitro programmed cell death.

Clusterin is a serum glycoprotein endowed with cell aggregating, complement inhibitory, and lipid binding properties, and is also considered as a specific marker of dying cells, its expression being increased in various tissues undergoing programmed cell death (PCD). However, no study has so far directly shown that cells expressing clusterin in these tissues are actually apoptotic as defined by morphological and biochemical criteria. We have studied cellular clusterin gene expression in vitro using three different models of PCD: (a) ultraviolet B (UV-B) irradiation of human U937, HeLa, and A431 cell lines, (b) in vitro aging of human peripheral blood neutrophils (PMNs), and (c) dexamethasone-induced cell death of the human lymphoblastoid cell line CEM-C7. In all three models, the classical morphological and biochemical features of PCD observed did not correlate with an increase, but with either a marked decrease or an absence of clusterin gene expression as assessed by Northern blot analysis. In situ hybridization of U937 and A431 cells after UV-B irradiation revealed, in addition, that only morphologically normal cells that are surviving continue to express the clusterin gene. Our results demonstrate that in the human myeloid, lymphoid, and epithelial cell types studied, clusterin gene expression is not a prerequisite to their death by apoptosis. In addition, and most interestingly, in situ hybridization of U937 and A431 cells revealed that only surviving cells express the clusterin gene after the induction of PCD, thus providing novel evidence suggesting that clusterin may be associated with cell survival within tissues regressing as a consequence of PCD.

Apoptosis↗
PubMed1995

Genesis of renal cysts is associated with clusterin expression in experimental cystic disease.

Phenol II is a cystogenic chemical that rapidly induces renal cysts, which regress after drug withdrawal. Cyst formation in this model parallels changes in the tubular basement membrane. Clusterin is a potent cohesive factor induced in states of tissue remodeling. The purpose of this study was to determine if renal clusterin was increased in the Phenol II model and to define the time course and distribution of its induction. Male Sprague-Dawley rats were given, by daily gavage, Phenol II (1.2 mg/kg per day) or vehicle (control). The kidneys were harvested after 1, 2, or 4 days of Phenol II treatment or 3 or 7 days after drug withdrawal. An increase in immunoreactive clusterin was seen in the kidneys of Phenol II-treated rats but not in controls. The appearance of clusterin followed a time course similar to that for cyst formation, with expression confined to the epithelial lining and intratubular casts of dilated or cystic tubules. After Phenol II withdrawal, renal cysts regressed and clusterin staining disappeared. The development of cysts was associated with an increase in clusterin mRNA that decreased after drug withdrawal. In conclusion, a marked, yet reversible induction of clusterin occurred in chemically induced polycystic kidney disease. The function of clusterin in this setting remains enigmatic.

Animals↗
PubMed1997

Thrombin increases clusterin mRNA in glomerular epithelial and mesangial cells.

Clusterin, a multifunctional protein with complement blocking activity, and fibrin, a product of thrombin's enzymatic activity, are present in the kidney during acute and chronic renal failure. The role of thrombin in regulating clusterin mRNA in the kidney is not known. The effect of thrombin on clusterin mRNA expression was examined in rat glomerular mesangial and glomerular epithelial cells, and cultured human renal proximal tubular epithelial cells by northern blot. Thrombin (10(-8) M) increased clusterin mRNA levels two- to fourfold in glomerular mesangial, glomerular epithelial, and proximal tubule epithelial cells. This was a specific effect of thrombin receptor activation because peptides corresponding to the tethered ligand of the thrombin receptor were also able to increase clusterin mRNA levels. Epidermal growth factor, insulin-like growth factor-1, and transforming growth factor-beta 1 had little or no effect on clusterin mRNA levels. The protein kinase C inhibitor RO-32-0432 (1 microM) inhibited the thrombin-induced increase in clusterin mRNA, suggesting that thrombin receptor activation may regulate renal clusterin mRNA levels through protein kinase C.

Animals↗
PubMed1999

Nerve growth factor and epidermal growth factor stimulate clusterin gene expression in PC12 cells.

Clusterin (apolipoprotein J) is an extracellular glycoprotein that might exert functions in development, cell death and lipid transport. Clusterin gene expression is elevated at sites of tissue remodelling, such as differentiation and apoptosis; however, the signals responsible for this regulation have not been identified. We use here the clusterin gene as a model system to examine expression in PC12 cells under the control of differentiation and proliferation signals produced by nerve growth factor (NGF) and by epidermal growth factor (EGF) respectively. NGF induced clusterin mRNA, which preceded neurite outgrowth typical of neuronal differentiation. EGF also activated the clusterin mRNA, demonstrating that both proliferation and differentiation signals regulate the gene. To localize NGF- and EGF-responsive elements we isolated the clusterin promoter and tested it in PC12 cell transfections. A 2.5 kb promoter fragment and two 1.5 and 0.3 kb deletion mutants were inducible by NGF and EGF. The contribution to this response of a conserved activator protein 1 (AP-1) motif located in the 0.3 kb fragment was analysed by mutagenesis. The mutant promoter was not inducible by NGF or EGF, which identifies the AP-1 motif as an element responding to both factors. Binding studies with PC12 nuclear extracts showed that AP-1 binds to this sequence in the clusterin promoter. These findings suggest that NGF and EGF, which give differential gene regulation in PC12 cells, resulting in neuronal differentiation and proliferation respectively, use the common Ras/extracellular signal-regulated kinase/AP-1 signalling pathway to activate clusterin expression.

Animals↗
PubMed2000

Detection of differentially expressed genes in lymphomas using cDNA arrays: identification of clusterin as a new diagnostic marker for anaplastic large-cell lymphomas.

This study reports the first use of gene array technology for the identification of a tumor-specific marker in lymphoid neoplasms. The differential gene expression of 31 hematopoietic cell lines, representing most major lymphoma subgroups of B- and T-cell origin, was assessed by hybridizing labeled complementary DNA to Atlas human expression arrays containing 588 genes. Genes known to be specific for B, T, or myelomonocytic lineages were appropriately identified in the arrays, validating the general utility of this approach. One gene, clusterin, not previously known to be expressed in lymphoid neoplasms, was specifically found in all 4 anaplastic large-cell lymphoma (ALCL) cell lines, but not in any of the 27 remaining tumor lines. Using a monoclonal antibody against clusterin, its differential expression was confirmed by Western blotting and immunohistochemistry. A total of 198 primary lymphomas (representing most major lymphoma subtypes), including 36 cases of systemic ALCL, were surveyed for clusterin expression by immunohistochemistry and Western blotting. All of the 36 ALCL cases marked for clusterin, with most cases showing moderate to strong staining in the majority of neoplastic cells. Clusterin expression was not related to expression of anaplastic lymphoma kinase-1. With 2 exceptions, none of the remaining 162 non-ALCL cases marked with the clusterin antibody, including Hodgkin disease and primary cutaneous ALCL. In reactive lymphoid tissues, only follicular dendritic cells and fibroblastic reticular cells exhibited staining. Clusterin is a highly conserved glycoprotein implicated in intercellular and cell matrix interactions, regulation of the complement system, lipid transport, stress responses, and apoptosis. Although its function in ALCL is unknown, the unique expression of clusterin within this category of lymphoma provides an additional marker for the diagnosis of ALCL. This study illustrates the enormous potential of gene array technologies for diagnostic marker discovery. (Blood. 2000;96:398-404)

Biomarkers, Tumor↗
PubMed2006

Evaluation of serum and urine clusterin as a potential tumor marker for urinary bladder cancer.

Clusterin is a stress-associated cytoprotective chaperone up-regulated by various apoptotic triggers in many cancers and neurodegenerative diseases. No valid information about serum or urine clusterin concentration in patiens with bladder cancer exists. Aim of our paper was evaluation of the urine and serum clusterin concentrations in individuals with bladder cancer. Blood and urine samples were used from 43 patients with urothelial tumors of the urinary bladder and from 50 patients with benign urological diseases. Blood and urine were collected before cystoscopy. Enzyme-linked immunosorbent assays (ELISA) were performed for clusterin from serum and urine. Serum clusterin was higher in individuals with bladder cancer (means 185,812.5 vs 171,946.5 kU/l, p=0.04). Sensitivity for bladder cancer detection was 73% and specificity 55% (AUC 0.63); efficacy was not sufficient. Urine values of clusterin were higher in individuals with bladder cancer (197.2 vs 67.7, p=0.0007). Sensitivity for bladder cancer detection was 49% and specificity 92% (AUC 0.75, LR+ 6.1, PPV+ 84%); diagnostic efficacy was sufficient. In conclusion, serum and urine clusterin can differ between bladder cancer patients and the control group. Urine clusterin could be the possible laboratory marker of bladder cancer. Further research is warranted to confirm findings in larger studies of various clinical status.

Aged↗
PubMed2005

Clusterin interacts with SCLIP (SCG10-like protein) and promotes neurite outgrowth of PC12 cells.

Clusterin has been known as a chaperone-like molecule capable of interacting with various proteins. In this study, we show that clusterin interacts with the microtubule-destabilizing stathmin family protein SCLIP by GST pull-down and co-immunoprecipitation assays. Interestingly, SCLIP interacts with 80 kDa mature form of clusterin in the cytosolic fraction of PC12 cells permeabilized by low concentration of a weak nonionic detergent digitonin, but not with intracellular variants of clusterin known as binding isoforms of Ku70 or TGF-beta receptors. Both clusterin and SCLIP are co-localized at the perinuclear region and growth cone of PC12 cells. In addition, we show that the minimal domains for the interaction are mapped to the C-terminal valine-rich region (367-447) of clusterin and the N-terminal palmitoylation and membrane attachment site (1-34) of SCLIP. Finally, we demonstrate that ectopic expression of clusterin in PC12 cells elongates neurite-formation triggered by NGF and induces spontaneous neurite outgrowth even in the absence of NGF. Taken together, these results suggest that the clusterin interacts with SCLIP and the interaction may act as an important modulator during neuronal differentiation.

Animals↗
PubMed1985

Immunolocalization of clusterin in the ram testis, rete testis, and excurrent ducts.

Clusterin, a glycoprotein that elicits cell aggregation, has previously been isolated from ram rete testis fluid, and has been partially characterized. In experiments reported, we have used monoclonal antibodies against clusterin in combination with indirect immunofluorescence microscopy to investigate the distribution of clusterin in the adult ram testis, rete testis, and excurrent ducts. Tissue blocks (5 mm3) were fixed in periodate/lysine/paraformaldehyde containing 0.1% glutaraldehyde and, after embedding, 5-microM sections were prepared for immunolocalization. In the testis, 2 basic patterns were observed: 1) strong to moderate staining for clusterin in the adluminal region with little staining in the basal region of the seminiferous epithelium and germinal cells; and 2) moderate staining throughout the seminiferous epithelium between germinal cells. In the rete testis, strong clusterin staining was localized intracellularly in the rete epithelial cells, most often associated with the luminal surface. In the epididymis, intracellular clusterin was localized in some principal cells of the caput epididymidis. The luminal surfaces and spermatozoa within the lumen were strongly positive. In the vas deferens, clusterin staining was associated with the luminal surface only. The presence of clusterin was clearly detected in unwashed isolated epididymal spermatozoa, but not in spermatozoa washed with phosphate-buffered saline containing 0.05% Tween 20.

Animals↗
PubMed2001

Expression of clusterin in the superficial zone of bovine articular cartilage.

OBJECTIVE: To investigate the differences between chondrocytes of the superficial and underlying zones of articular cartilage at the level of gene expression. METHODS: Messenger RNA (mRNA) was isolated from chondrocytes harvested from the superficial and deep zones of immature bovine articular cartilage. This mRNA was reverse transcribed, radiolabeled, and then each complementary DNA (cDNA) sample was used to screen duplicate filters of a bovine chondrocyte cDNA library. By comparing autoradiographic signals on matching filter sets, clones exclusively expressed in the superficial zone of articular cartilage were isolated and characterized further. RESULTS: Of the superficial-specific gene clones isolated, 25% were found to be a single gene product, clusterin. Northern hybridization was used to show that clusterin is expressed specifically in the superficial zone of articular cartilage and that its expression is up-regulated in mature cartilage. In situ hybridization was used to precisely localize clusterin transcripts in articular cartilage, where it was found that clusterin expression was confined to the articular surface in both immature and mature samples. CONCLUSION: The discovery of clusterin expression at the articular cartilage surface extends previous observations that superficial articular chondrocytes are highly specialized cells. Clusterin is a multifunctional, secreted glycoprotein that has been shown to be expressed in diverse locations that have in common a tissue-fluid boundary. Additionally, clusterin has been implicated in regulating complement activation and cell death in injured and degenerating tissues.

Animals↗
PubMed1995

Clusterin expression within skin correlates with hair growth.

Clusterin/TRPM-2 is a sulfated glycoprotein that is expressed in many tissues. Independently cloned and isolated by several laboratories, it bears many names, and has been shown to be involved in many processes. These include cell-cell adhesion and aggregation, inhibition of complement cytolysis, programmed cell death and apoptosis, tissue remodeling, and terminal differentiation. The hair follicle undergoes cycles of growth, regression, and rest, which involve both tissue remodeling and programmed cell death. To identify whether clusterin expression is involved in hair growth and cycling, we studied the expression of clusterin throughout the hair cycle. We demonstrate that clusterin is expressed during the growth phase of the hair cycle. We found no correlation between clusterin expression and the apoptotic regression of the hair follicle. Using immunohistochemistry we localized clusterin to the inner root sheath of the follicle. This suggests that clusterin might be involved in the morphogenesis and differentiation of the hair follicle. We propose that clusterin has a role in the maintenance of the layered structure of the hair follicle, and in the interactions between the inner root sheath and both the outer root sheath and the

Amino Acid Sequence↗
PubMed1993

Clusterin levels increase during neuronal development.

The expression of clusterin has been shown to be elevated in several models of experimentally induced programmed cell death and in association with a number of neurodegenerative conditions. In order to test whether this protein is expressed in neurons during development, the expression of clusterin was examined in the developing nervous system, using immunohistochemistry and mRNA analysis. Clusterin expression was observed in the earliest neurons of the cortical plate on embryonic day (E) 12. Thereafter, the intensity of clusterin staining continued to increase in an age-dependent manner, with the greatest intensity of staining being found in the postnatal mature brain. Virtually all neurons were clusterin-positive and there was no evidence for the appearance of clusterin-positive cells specifically during epochs of programmed neuronal death in the embryo. This study suggests that clusterin has a role in neuronal maturation and it is unlikely to be associated exclusively with neuronal cell death.

Animals↗