Heat shock protects cardiac cells from doxorubicin-induced toxicity by activating p38 MAPK and phosphorylation of small heat shock protein 27. 2006

C D Venkatakrishnan, and Arun K Tewari, and Leni Moldovan, and Arturo J Cardounel, and Jay L Zweier, and Periannan Kuppusamy, and Govindasamy Ilangovan
Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.

Doxorubicin (DOX) and its derivatives are used as chemotherapeutic drugs to treat cancer patients. However, production of DOX-mediated reactive oxygen species (ROS) by prolonged use of these drugs has been found to cause dilative cardiomyopathy and congestive heart failure. Thus various preventive modalities have been developed to avoid this side effect. We have found that the DOX-mediated oxidant-induced toxicity in cardiac cells could be minimized by hyperthermia-induced small heat shock protein 27 (HSP27); that is, this protein acts as an endogenous antioxidant against DOX-derived oxidants such as H(2)O(2). Heat shock-induced HSP27 was found to act as an antiapoptotic protein (reducing ROS and Bax-to-Bcl2 ratio) against DOX, and its phosphorylated isoforms stabilized F-actin remodeling in DOX-treated cardiac cells and, hence, attenuated the toxicity. Protein kinase assays and proteomic analyses suggested that higher expression of HSP27 and its phosphorylation are responsible for the protection in heat-shocked cells. Two-dimensional gel electrophoresis showed six isoforms (nonphosphorylated and phosphorylated) of HSP27. Matrix-assisted laser desorption/ionization time of flight analyses showed alpha- and beta-isoforms of HSP27, which are phosphorylated by various protein kinases. Ser(15) and Ser(85) phosphorylation of HSP27 by MAPK-assisted protein kinase 2 was found to be the key mechanism in reduction of apoptosis and facilitation of F-actin remodeling. The present study illustrates that hyperthermia protects cells from DOX-induced death through induction and phosphorylation of HSP27 and its antiapoptotic and actin-remodeling activities.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009363 Neoplasm Proteins Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm. Proteins, Neoplasm
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004317 Doxorubicin Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN. Adriamycin,Adriablastin,Adriablastine,Adriblastin,Adriblastina,Adriblastine,Adrimedac,DOXO-cell,Doxolem,Doxorubicin Hexal,Doxorubicin Hydrochloride,Doxorubicin NC,Doxorubicina Ferrer Farm,Doxorubicina Funk,Doxorubicina Tedec,Doxorubicine Baxter,Doxotec,Farmiblastina,Myocet,Onkodox,Ribodoxo,Rubex,Urokit Doxo-cell,DOXO cell,Hydrochloride, Doxorubicin,Urokit Doxo cell
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006360 Heat-Shock Proteins Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions. Stress Protein,Stress Proteins,Heat-Shock Protein,Heat Shock Protein,Heat Shock Proteins,Protein, Stress
D000199 Actins Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle. F-Actin,G-Actin,Actin,Isoactin,N-Actin,alpha-Actin,alpha-Isoactin,beta-Actin,gamma-Actin,F Actin,G Actin,N Actin,alpha Actin,alpha Isoactin,beta Actin,gamma Actin
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

Related Publications

C D Venkatakrishnan, and Arun K Tewari, and Leni Moldovan, and Arturo J Cardounel, and Jay L Zweier, and Periannan Kuppusamy, and Govindasamy Ilangovan
September 2005, Journal of cellular biochemistry,
C D Venkatakrishnan, and Arun K Tewari, and Leni Moldovan, and Arturo J Cardounel, and Jay L Zweier, and Periannan Kuppusamy, and Govindasamy Ilangovan
March 2009, Pediatric research,
C D Venkatakrishnan, and Arun K Tewari, and Leni Moldovan, and Arturo J Cardounel, and Jay L Zweier, and Periannan Kuppusamy, and Govindasamy Ilangovan
August 2007, European journal of heart failure,
C D Venkatakrishnan, and Arun K Tewari, and Leni Moldovan, and Arturo J Cardounel, and Jay L Zweier, and Periannan Kuppusamy, and Govindasamy Ilangovan
February 1997, Journal of cell science,
C D Venkatakrishnan, and Arun K Tewari, and Leni Moldovan, and Arturo J Cardounel, and Jay L Zweier, and Periannan Kuppusamy, and Govindasamy Ilangovan
April 2020, Movement disorders : official journal of the Movement Disorder Society,
C D Venkatakrishnan, and Arun K Tewari, and Leni Moldovan, and Arturo J Cardounel, and Jay L Zweier, and Periannan Kuppusamy, and Govindasamy Ilangovan
June 2004, Circulation research,
C D Venkatakrishnan, and Arun K Tewari, and Leni Moldovan, and Arturo J Cardounel, and Jay L Zweier, and Periannan Kuppusamy, and Govindasamy Ilangovan
January 2020, Oxidative medicine and cellular longevity,
C D Venkatakrishnan, and Arun K Tewari, and Leni Moldovan, and Arturo J Cardounel, and Jay L Zweier, and Periannan Kuppusamy, and Govindasamy Ilangovan
September 2009, Cell stress & chaperones,
C D Venkatakrishnan, and Arun K Tewari, and Leni Moldovan, and Arturo J Cardounel, and Jay L Zweier, and Periannan Kuppusamy, and Govindasamy Ilangovan
May 2017, Cell stress & chaperones,
C D Venkatakrishnan, and Arun K Tewari, and Leni Moldovan, and Arturo J Cardounel, and Jay L Zweier, and Periannan Kuppusamy, and Govindasamy Ilangovan
April 2009, Journal of medicinal chemistry,
Copied contents to your clipboard!