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Apoptosis: Cellular Signaling and Molecular Mechanisms
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
Rosemary B. Evans, John A. Cidlowski
A set of testosterone-repressed mRNA’s (TRPM’s) were identified in rat involuting ventral prostate.55 One of these genes, TRPM-2, is identical to sulfated glycoprotein-2 (SGP-2) in all but its 5′ region, which appears to vary due to different exon 1 usage.56 These proteins are also known as clusterin.57 This highly conserved gene has been isolated from a variety of species and tissues.58 Expression of this gene also is increased during renal atrophy following ureter obstruction, during the death of interdigital tissues, and in the chemotherapeutic regression of certain tumors. Expression of clusterin, however, is not observed during apoptosis in leukocytes induced by glucocorticoid or Ca2+ ionophore treatment, or during programmed cell death of aged neutrophils, neurons, or palatal shelf epithelium during development. Therefore, the requirement for this protein during apoptosis may be cell type specific.2,58
Principles of Clinical Pathology
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Niraj K. Tripathi, Jacqueline M. Tarrant
Clusterin is a secreted glycoprotein that is widely expressed in the kidney; however, due to its size (80kD), clusterin in the blood should be excluded from filtration through the glomerulus. Urine clusterin is a pan-nephric urine biomarker (Wadey et al. 2014; Correa-Rotter et al. 1998) and is induced and secreted during kidney injury and repair. Additionally, as a ligand of transporters in the proximal tubule, it is also a marker of tubular function. Clusterin is a component of seminal fluid (Rosenberg and Silkensen 1995) and, therefore, may be higher in males of those species where seminal fluid can be found in urine (e.g., rat, dog).
Early detection of dementia
Published in Stephen Curran, John P. Wattis, Practical Management of Dementia, 2018
Sonja Krüger, Miguel A. Bertoni, Stephen Curran
As can be predicted, not all the consequences of early detection are necessarily positive. The diagnosis will be stressful for patients and carers and because the natural history of dementia is well known, it can be an alarming diagnosis and can result in a range of psychological reactions, including ‘shock and bewilderment’ initially, followed by a range of emotions such as anger, depression and denial. However a particular patient and their family copes with the diagnosis, it is nearly always stressful and it has a dramatic impact on their lives and future plans. If the diagnosis subsequently turns out to be wrong, the consequences can be devastating and patients and their families will feel very angry. If possible pre- and post-diagnostic counselling should be available, but this is rarely the case. This will become more of a priority if the ‘Holy Grail’ of a blood test for AD that can predict the clinical onset of the disease becomes a reality. Some recent promising work has demonstrated an association of plasma clusterin concentration with severity, pathology and progression of AD.4
The case for complement component 5 as a target in neurodegenerative disease
Published in Expert Opinion on Therapeutic Targets, 2023
Amelia Stennett, Kallie Friston, Claire L. Harris, Adam J. M. Wollman, Agnieszka K. Bronowska, Katrina S. Madden
AD is particularly well-researched, with animal models providing evidence to place dysregulated complement at the forefront of ND, specifically in the context of neuroinflammation. Use of mouse knock-out strains and judicious tissue staining puts C1q, C3 and the C5 activation products in the spotlight [30,46–63]. Compelling evidence comes from a study where DBA/2 J mice, which are deficient in C5, and C57Bl6 mice transgenic for the human APP gene were compared, with a lower amyloid burden and milder pathology observed in DBA/2 J mice [64]. Recent investigations using C6-deficient mice and a C7-blocking antibody strongly suggest that MAC, rather than C5a, may be a critical player in synapse loss in several murine AD models [65]. Importantly, animal model data are backed by genetic associations [66,67] between complement and AD include clusterin and CD35 (complement receptor 1, CR1), suggesting a role for complement control in disease etiology [68–70]. The role of clusterin is unclear- while it does inhibit the MAC, it also binds debris and likely accumulates on amyloid plaques. Critically, however, CR1 controls the complement cascade and is one of the few control proteins that is capable of directly inhibiting C5 convertase, potentially indicating a role for C5 in AD [30,68]. Despite the accumulating evidence for a role of the complement terminal pathway in AD, challenges of early diagnosis, understanding of the stage of disease in which complement plays a role and access of drugs to the CNS tissue continues to hamper progression into clinical trials.
Increased plasma clusterin and miR-21 in acute pancreatitis
Published in British Journal of Biomedical Science, 2021
Clusterin is a secretory glycoprotein that is highly induced in several tissues in response to injury, being expressed in various tissues such as brain, ovary, testis, heart, and blood vessels, from which it may be secreted to the circulation [8–10]. Most attacks of display a self-limiting course, suggesting that pancreatic acinar cells may be able to protect themselves against cellular injury, thus preventing further progression of the disease. In experimental pancreatitis in vitro and in vivo, clusterin mRNA was expressed after 4 hours and peaked at 8 and 24 hours, whereas DNA fragmentation peaked at 72 hours, suggesting that clusterin is a defence mechanism of the exocrine pancreas. Like miR-21, we report raised clusterin in acute pancreatitis, with levels peaking late (48–72 hours, as did amylase), and accordingly may be of little value in diagnosing acute pancreatitis, as the relative increases in both amylase and lipase are greater. However, unlike these two markers, and all LFTs, levels of clusterin increased in a significant linear manner with disease severity, suggesting it has a role as a marker in this respect.
Comparison of several commonly used detection indicators of cell senescence
Published in Drug and Chemical Toxicology, 2020
Yuanyuan Xiao, Yiyuan Zhang, Fang Xiao
Clusterin, which was originally identified as serum apolipoprotein J, is known as a stress-inducible pro-survival extracellular chaperone that is implicated in various biological processes including immune modulation, lipid transportation, and cancer cell survival (Trougakos and Gonos 2002). Clusterin is considered as a biomarker of senescence since it has been found to be transcriptionally up-regulated during cellular senescence and age-related disorders such as Alzheimer’s disease (Petropoulou et al. 2001, Thambisetty et al. 2010). Clusterin expression can be detected using real-time quantitative PCR (qPCR) or western blotting. It is reported that WI-38 fibroblasts exposed to a subcytotoxic concentration of copper sulfate presented inhibited cell proliferation, increased SA-β gal activity, and enhanced expression of Clusterin (Matos et al. 2012). Copper was also shown to induce cellular senescence in human tumor cells such as glioblastoma multiforme (GBM) cells, which was also characterized by the over-expression of Clusterin (Li et al. 2013). The induction of tumor cells into the state of irreversible growth arrest could provide a useful in vitro model for developing novel therapeutic strategy for cancer treatments. Studies have demonstrated that Clusterin is also abnormally up-regulated in numerous advanced and metastatic cancers including renal, breast, ovarian, colon, cervical cancers, hepatocarcinoma, and lymphoma (Zhou et al. 2015), which is in line with its anti-apoptotic function (Zhong et al. 2010). Therefore, when using Clusterin as biomarker of cellular senescence, other detection indicators should be also included for a comprehensive consideration.