Clusterin/Apolipoprotein J in human aging and cancer

Trougakos, Ioannis P.; Gonos, Efstathios S.

doi:10.1016/s1357-2725(02)00041-9

Cited by 332 publications

(301 citation statements)

References 167 publications

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“…Clusterin/ApoJ expression has been implicated in tumorigenesis [18], through its anti-apoptotic properties. Overexpression of clusterin/ApoJ cDNA into human cancer cell lines greatly improved their ability to resistant chemotherapy, through inhibition of apoptosis both in vitro and in vivo [23,32,33].…”

Section: Discussionmentioning

confidence: 99%

“…In agreement with previous studies on the various forms of ApoJ and their processing, a diffuse doublet of 36-40 kD band that corresponds to α-and β-chains of the secreted 75-80 kD clusterin/ApoJ was detected as the cleavage product at the Asp 227 -Ser 228 residues after the reduction of the protein (sClu). And a 60 kD band that corresponds to the cytoplasmic form of clusterin/Apo J (cClu) which is not reduced still retained inside the cells [18,28]. Similarly, human clusterin/ApoJ was also overexpressed in HaCaTApoJ clone 2.…”

Section: Generation and Characterization Of Human Clusterin/ Apoj-expmentioning

confidence: 99%

“…Although the anti-apoptotic role of Bcl-2 to various toxic agents and stress stimuli is wellestablished [16], that of clusterin/ApoJ is still under investigation [17,18]. Clusterin is ubiquitously expressed, implicated in a number of physiological functions and is induced in diverse diseases and stress stimuli such as heat shock and oxidative stress, cytokines and growth factors, chemotherapeutic agents, ultraviolet and ionizing radiation.…”

Section: Introductionmentioning

confidence: 99%

“…Clusterin is ubiquitously expressed, implicated in a number of physiological functions and is induced in diverse diseases and stress stimuli such as heat shock and oxidative stress, cytokines and growth factors, chemotherapeutic agents, ultraviolet and ionizing radiation. This led to suggestion that it may play a role in membrane lipid cycling, apoptotic cell death, and as a stress-induced secreted chaperone protein [17,18]. Overexpression of the secreted form of clusterin/ApoJ in human tumor cells would induce resistance to TNFα- [19,20], Fas- [21], oxidative stress- [22] or chemotherapy-mediated apoptosis [23].…”

Section: Introductionmentioning

confidence: 99%

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Ectopic expression of clusterin/apolipoprotein J or Bcl-2 decreases the sensitivity of HaCaT cells to toxic effects of ropivacaine

et al. 2004

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Local anesthetics inhibit cell proliferation and induce apoptosis in various cell types. Ropivacaine, a unique, novel tertiary amine-type anesthetic, was shown to inhibit the proliferation of several cell types including keratinocytes. We found that Ropivacaine could inhibit the proliferation and induce apoptosis in an immortalized human keratinocyte line, HaCaT, in a dose-and time-dependent manner and with the deprivation of serum. The dose-dependent induction of apoptosis by ropivacaine was demonstrated by DNA fragmentation analysis and the proteolytic cleavage of a caspase-3 substrate -poly (ADP-ribose) polymerase (PARP). In addition, ropivacaine downregulated the expression of clusterin/ apoliporotein J, a protein with anti-apoptotic properties, in a dose-dependent manner, which well correlated with the induction of apoptosis of HaCaT cells. To investigate the role of clusterin/apoliporotein J in ropivacaine-induced apoptosis, HaCaT cells overexpressing clusterin/apoliporotein J were generated and compared to cells expressing the well established anti-apoptotic Bcl-2 protein. Ectopic overexpression of the secreted form of clusterin/apoliporotein J or Bcl-2 decreased the sensitivity of HaCaT cells to toxic effects of ropivacaine as demonstrated by DNA fragmentation, the proteolytic cleavage of PARP and by a reduction in procaspase-3 expression. Furthermore, the downregulation of endogenous clusterin/apolipoprotein J levels by ropivacaine suggested that this might be one mechanism by which ropivacaine induced cell death in HaCaT cells. In conclusion, the ability of ropivacaine to induce antiproliferative responses and to suppress the expression of the anti-apoptotic protein clusterin/apolipoprotein J, combined with previously reported anti-inflammatory activity and analgesic property of the drug, suggests that ropivacaine may have potential utility in the local treatment of tumors.

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Section: Discussionmentioning

confidence: 99%

Section: Generation and Characterization Of Human Clusterin/ Apoj-expmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ectopic expression of clusterin/apolipoprotein J or Bcl-2 decreases the sensitivity of HaCaT cells to toxic effects of ropivacaine

et al. 2004

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“…There are a number of synonyms for clusterin, including T64, SGP-2, TRPM-2, gp80, and Gp-Ш. Clusterin has been found in all body fluids [36]. The human homolog of clusterin has also been given other names, including complement-lysis inhibitor (CLI), secreted protein 40 (SP-40), and apolipoprotein J (ApoJ).…”

Section: Introductionmentioning

confidence: 99%

Presence, localization, and origin of clusterin in normal human spermatozoa

Han

Wang

Cheng

et al. 2012

J Assist Reprod Genet

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Purpose Clusterin in mammalian semen is a secretory form of clusterin (sCLU) with the heterodimeric structure. It is secreted by the epididymis and seminal vesicle. It is generally agreed that clusterin mainly exists on the surface of abnormal spermatozoa and is implicated in decreased sperm motility, sperm aggregation and infertility. However, few studies observe clusterin in normal spermatozoa, which is presumed to be a novel form. Up to now, the systematical information about the presence, localization, origin and function of clusterin in normal human spermatozoa has yet not been established. The aim of our current study is to systematically research clusterin in normal human spermatozoa.Methods We detected the presence of clusterin via western blot, explored the localization of clusterin using immunofluorescence, and investigated the origin and distribution of clusterin in human testis by western blot and immunohistochemistry. Results We found native clusterin in the inner plasma membrane of normal human spermatozoa. It was derived from the testis and showed similar molecular weight and heterodimeric structure compared with sCLU in semen and on the surface of abnormal spermatozoa. Conclusion Clusterin in normal spermatozoa should be self-synthesized during the later stage of spermatogenesis. The different localization and origin suggested that the clusterin observed by us may be a novel form compared with conventional sCLU on the surface of abnormal spermatozoa.

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Low‐power millimeter wave radiations do not alter stress‐sensitive gene expression of chaperone proteins

Zhadobov

Sauleau

Coq

et al. 2006

Bioelectromagnetics

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This article reports experimental results on the influence of low-power millimeter wave (MMW) radiation at 60 GHz on a set of stress-sensitive gene expression of molecular chaperones, namely clusterin (CLU) and HSP70, in a human brain cell line. Selection of the exposure frequency is determined by its near-future applications for the new broadband civil wireless communication systems including wireless local area networks (WLAN) for domestic and professional uses. Frequencies around 60 GHz are strongly attenuated in the earth's atmosphere and such radiations represent a new environmental factor. An exposure system operating in V-band (50-75 GHz) was developed for cell exposure. U-251 MG glial cell line was sham-exposed or exposed to MMW radiation for different durations (1-33 h) and two different power densities (5.4 microW/cm(2) or 0.54 mW/cm(2)). As gene expression is a multiple-step process, we analyzed chaperone proteins induction at different levels. First, using luciferase reporter gene, we investigated potential effect of MMWs on the activation of transcription factors (TFs) and gene promoter activity. Next, using RT-PCR and Western blot assays, we verified whether MMW exposure could alter RNA accumulation, translation, or protein stability. Experimental data demonstrated the absence of significant modifications in gene transcription, mRNA, and protein amount for the considered stress-sensitive genes for the exposure durations and power densities investigated. The main results of this study suggest that low-power 60 GHz radiation does not modify stress-sensitive gene expression of chaperone proteins.

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Clusterin/Apolipoprotein J in human aging and cancer

Cited by 332 publications

References 167 publications

Ectopic expression of clusterin/apolipoprotein J or Bcl-2 decreases the sensitivity of HaCaT cells to toxic effects of ropivacaine

Ectopic expression of clusterin/apolipoprotein J or Bcl-2 decreases the sensitivity of HaCaT cells to toxic effects of ropivacaine

Presence, localization, and origin of clusterin in normal human spermatozoa

Low‐power millimeter wave radiations do not alter stress‐sensitive gene expression of chaperone proteins

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