Heat shock protein 27 interacts with vimentin and prevents insolubilization of vimentin subunits induced by cadmium

Abstract

Vimentin is an intermediate filament that regulates cell attachment and subcellular organization. In this study, vimentin filaments were morphologically altered, and its soluble subunits were rapidly reduced via cadmium chloride treatment. Cadmium chloride stimulated three major mitogen-activated protein kinases (MAPKs): extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, and led apoptotic pathway via caspase-9 and caspase-3 activations. In order to determine whether MAPKs were involved in this cadmium-induced soluble vimentin disappearance, we applied MAPK-specific inhibitors (PD98059, SP600125, SB203580). These inhibitors did not abolish the cadmium-induced soluble vimentin disappearance. Caspase and proteosome degradation pathway were also not involved in soluble vimentin disappearance. When we observed vimentin levels in soluble and insoluble fractions, soluble vimentin subunits shifted to an insoluble fraction. As we discovered that heat-shock protein 27 (HSP27) was colocalized and physically associated with vimentin in unstressed cells, the roles of HSP27 with regard to vimentin were assessed. HSP27-overexpressing cells prevented morphological alterations of the vimentin filaments, as well as reductions of soluble vimentin, in the cadmium-treated cells. Moreover, HSP27 antisense oligonucleotide augmented these cadmium-induced changes in vimentin. These findings indicate that HSP27 prevents disruption of the vimentin intermediate filament networks and soluble vimentin disappearance, by virtue of its physical interaction with vimentin in cadmium-treated SK-N-SH cells.

The small heat shock protein, HSP30, is associated with aggresome-like inclusion bodies in proteasomal inhibitor-, arsenite-, and cadmium-treated Xenopus kidney cells

“…Support for this possibility in A6 cells was shown by our finding that stress-induced accumulation of HSP30 occurred in the insoluble as well as soluble cellular protein fraction. Similarly, in studies with mammalian cells, it was determined that proteasomal inhibition, sodium arsenite or cadmium chloride treatment induced the accumulation of the small HSPs, HSP25, HSP27, or αΒ-crystallin in both soluble and insoluble fractions (Ito et al, 2002;Lee et al, 2005;Vertii et al, 2006;Bolhuis and Richter-Landsberg, 2010). In contrast to the above theory, it was…”

Distal hereditary motor neuropathy in Korean patients with a small heat shock protein 27 mutation

“…The expression of HSP27 is induced in response to various environmental challenges and developmental transitions (Lee et al, 2005;Arya et al, 2007). As a molecular chaperone, HSP27 protein protects cells from stress, blocks apoptosis signals, and is involved in cell motility and cytoskeletal stabilization (Wagstaff et al, 1999;Hirano et al, 2004;Heo et al, 2006;Williams et al, 2006;Arrigo et al, 2007).…”

Proteomic Analysis Revealed the Important Role of Vimentin in Human Cervical Carcinoma HeLa Cells Treated With Gambogic Acid

“…In the present study, HSP27 was found to be a targetrelated protein of GA at early stage (3 h) of treatment. HSP27 could be regulated by p38 MAPK pathway (39) and could interact directly with vimentin (40,41). Results of Western blotting assay confirmed that GA treatment induced increase in phosphorylation of p38 and MAPKAPK2, the kinase that could phosphorylate HSP27 after activation of p38 MAPK pathway (42).…”