NDLI: Recombinant heat shock protein 27 (HSP27/HSPB1) protects against cadmium-induced oxidative stress and toxicity in human cervical cancer cells

Content Provider	Springer Nature Link
Author	Alvarez Olmedo, Daiana G. Biaggio, Veronica S. Koumbadinga, Geremy A. Gómez, Nidia N. Shi, Chunhua Ciocca, Daniel R. Batulan, Zarah Fanelli, Mariel A. O’Brien, Edward R.
Copyright Year	2017
Abstract	Cadmium (Cd) is a carcinogen with several well-described toxicological effects in humans, but its molecular mechanisms are still not fully understood. Overexpression of heat shock protein 27 (HSP27/HSPB1)—a multifunctional protein chaperone—has been shown to protect cells from oxidative damage and apoptosis triggered by Cd exposure. The aims of this work were to investigate the potential use of extracellular recombinant HSP27 to prevent/counteract Cd-induced cellular toxicity and to evaluate if peroxynitrite was involved in the development of Cd-induced toxicity. Here, we report that the harmful effects of Cd correlated with changes in oxidative stress markers: upregulation of reactive oxygen species, reduction in nitric oxide (NO) bioavailability, increment in lipid peroxidation, peroxynitrite (PN), and protein nitration; intracellular HSP27 was reduced. Treatments with Cd (100 μM) for 24 h or with the peroxynitrite donor, SIN-1, decreased HSP27 levels (~50%), suggesting that PN formation is responsible for the reduction of HSP27. Pre-treatments of the cells either with Nω-nitro-l-arginine methyl ester hydrochloride (L-NAME) (a pharmacological inhibitor of NO synthase) or with recombinant HSP27 (rHSP27) attenuated the disruption of the cellular metabolism induced by Cd, increasing in a 55 and 52%, respectively, the cell viability measured by CCK-8. Cd induced necrotic cell death pathways, although apoptosis was also activated; pre-treatment with L-NAME or rHSP27 mitigated cell death. Our findings show for the first time a direct relationship between Cd-induced toxicity and PN production and a role for rHSP27 as a potential therapeutic agent that may counteract Cd toxicity.
Starting Page	357
Ending Page	369
Page Count	13
File Format	PDF
ISSN	13558145
Journal	Cell Stress and Chaperones
Volume Number	22
Issue Number	3
e-ISSN	14661268
Language	English
Publisher	Springer Netherlands
Publisher Date	2017-03-24
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Heat shock protein 27 (HSP27) Cytoprotection Signaling cadmium toxicity Oxidative stress Biomedicine Cell Biology Biochemistry Immunology Cancer Research Neurosciences
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry

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