Effect of an experimental proteasome inhibitor on the cytoskeleton, cytosolic protein turnover, and induction in the neuronal cells in vitro

Csizmadia, Vilmos; Raczynski, Arek; Csizmadia, Eva; Fedyk, Eric R.; Rottman, James B.; Alden, Carl L.

doi:10.1016/j.neuro.2007.11.003

Cited by 29 publications

(27 citation statements)

References 37 publications

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“…Cytoskeletal disruption in response to proteasomal inhibition has been reported in both mammals and plants (Sheng et al 2006;Csizmadia et al 2008). In A6 cells, the actin cytoskeleton was also reported to be sensitive to other stresses including heat shock, sodium arsenite, and cadmium chloride exposure (Gellalchew and Heikkila 2005;Manwell and Heikkila 2007;Voyer and Heikkila 2008;Woolfson and Heikkila 2009).…”

Section: Discussionmentioning

confidence: 99%

“…In A6 cells, the actin cytoskeleton was also reported to be sensitive to other stresses including heat shock, sodium arsenite, and cadmium chloride exposure (Gellalchew and Heikkila 2005;Manwell and Heikkila 2007;Voyer and Heikkila 2008;Woolfson and Heikkila 2009). While the exact mechanism for proteasome inhibitor-induced cytoskeletal disruption is not known, it has been suggested that the accumulation of unfolded proteins may activate a signal transduction cascade that activates numerous cellular events including cytoskeletal dysregulation (Csizmadia et al 2008).…”

Section: Discussionmentioning

confidence: 99%

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Proteasome inhibition induces hsp30 and hsp70 gene expression as well as the acquisition of thermotolerance in Xenopus laevis A6 cells

Young

Heikkila

2010

Cell Stress and Chaperones

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Previous studies have shown that inhibiting the activity of the proteasome leads to the accumulation of damaged or unfolded proteins within the cell. In this study, we report that proteasome inhibitors, lactacystin and carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132), induced the accumulation of ubiquitinated proteins as well as a dose-and time-dependent increase in the relative levels of heat shock protein (HSP)30 and HSP70 and their respective mRNAs in Xenopus laevis A6 kidney epithelial cells. In A6 cells recovering from MG132 exposure, HSP30 and HSP70 levels were still elevated after 24 h but decreased substantially after 48 h. The activation of heat shock factor 1 (HSF1) may be involved in MG132-induced hsp gene expression in A6 cells since KNK437, a HSF1 inhibitor, repressed the accumulation of HSP30 and HSP70. Exposing A6 cells to simultaneous MG132 and mild heat shock enhanced the accumulation of HSP30 and HSP70 to a much greater extent than with each stressor alone. Immunocytochemical studies determined that HSP30 was localized primarily in the cytoplasm of lactacystin-or MG132-treated cells. In some cells treated with higher concentrations of MG132 or lactacystin, we observed in the cortical cytoplasm (1) relatively large HSP30 staining structures, (2) colocalization of actin and HSP30, and (3) cytoplasmic areas that were devoid of HSP30. Lastly, MG132 treatment of A6 cells conferred a state of thermotolerance such that they were able to survive a subsequent thermal challenge.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Proteasome inhibition induces hsp30 and hsp70 gene expression as well as the acquisition of thermotolerance in Xenopus laevis A6 cells

Young

Heikkila

2010

Cell Stress and Chaperones

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“…It is thought that bortezomib mainly causes direct dorsal root ganglion toxicity, based on studies in mice, which showed that ubiquitinated aggregates accumulated in the cytoplasm of the dorsal root ganglion. [32][33][34] There is now substantial experience regarding bortezomib-induced PN, and a number of excellent reviews provide a comprehensive overview of its etiology, clinical characteristics, and management. [35][36][37][38] Bortezomib-induced PN can be effectively managed with dose modification and is generally reversible in more than 50% of cases, with weekly dosing [39][40][41] and subcutaneous administration of bortezomib providing approaches to limit treatment-emergent PN, as described in more detail later.…”

Section: Bortezomib Establishing Efficacy and Safety: Initial Studiesmentioning

confidence: 99%

Proteasome inhibitors in multiple myeloma: 10 years later

Moreau

Richardson

Cavo

et al. 2012

Blood

449

369

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Proteasome inhibition has emerged as an important therapeutic strategy in multiple myeloma (MM). Since the publication of the first phase 1 trials of bortezomib 10 years ago, this first-in-class proteasome inhibitor (PI) has contributed substantially to the observed improvement in survival in MM patients over the past decade. Although first approved as a single agent in the relapsed setting, bortezomib is now predominantly used in combination regimens. Furthermore, the standard twice-weekly schedule may be replaced by weekly infusion, especially when bortezomib is used as part of combination regimens in frontline therapy.

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“…Most evidence is from somatic cells. Csizmadia et al [63] reported that the proteasome inhibitor EPI (experimental proteasome inhibitor) induced reorganization and relocation of nonubiquinated actin microfilaments and microtubules. Ubiquitination of the Lys118 residue of actin imparts one or more conformations that may be involved in regulation of muscle contractile activity [64].…”

Section: Uchl1 In Mammalian Oocytesmentioning

confidence: 99%

Role of Ubiquitin C-Terminal Hydrolase-L1 in Antipolyspermy Defense of Mammalian Oocytes1

Šušor

Lišková

Toralova

et al. 2010

Biology of Reproduction

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The ubiquitin-proteasome system regulates many cellular processes through rapid proteasomal degradation of ubiquitin-tagged proteins. Ubiquitin C-terminal hydrolase-L1 (UCHL1) is one of the most abundant proteins in mammalian oocytes. It has weak hydrolytic activity as a monomer and acts as a ubiquitin ligase in its dimeric or oligomeric form. Recently published data show that insufficiency in UCHL1 activity coincides with polyspermic fertilization; however, the mechanism by which UCHL1 contributes to this process remains unclear. Using UCHL1-specific inhibitors, we induced a high rate of polyspermy in bovine zygotes after in vitro fertilization. We also detected decreased levels in the monomeric ubiquitin and polyubiquitin pool. The presence of UCHL1 inhibitors in maturation medium enhanced formation of presumptive UCHL1 oligomers and subsequently increased abundance of K63-linked polyubiquitin chains in oocytes. We analyzed the dynamics of cortical granules (CGs) in UCHL1-inhibited oocytes; both migration of CGs toward the cortex during oocyte maturation and fertilization-induced extrusion of CGs were impaired. These alterations in CG dynamics coincided with high polyspermy incidence in in vitro-produced UCHL1-inhibited zygotes. These data indicate that antipolyspermy defense in bovine oocytes may rely on UCHL1-controlled functioning of CGs.

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Effect of an experimental proteasome inhibitor on the cytoskeleton, cytosolic protein turnover, and induction in the neuronal cells in vitro

Cited by 29 publications

References 37 publications

Proteasome inhibition induces hsp30 and hsp70 gene expression as well as the acquisition of thermotolerance in Xenopus laevis A6 cells

Proteasome inhibition induces hsp30 and hsp70 gene expression as well as the acquisition of thermotolerance in Xenopus laevis A6 cells

Proteasome inhibitors in multiple myeloma: 10 years later

Role of Ubiquitin C-Terminal Hydrolase-L1 in Antipolyspermy Defense of Mammalian Oocytes1

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