HSP90 Heat-Shock Proteins

Publication Title: 
Antimicrobial Agents and Chemotherapy

Previous studies have shown an antimalarial effect of total alkaloids extracted from leaves of Guiera senegalensis from Mali in West Africa. We independently observed that the beta-carboline alkaloid harmine obtained from a natural product library screen inhibited Plasmodium falciparum heat shock protein 90 (PfHsp90) ATP-binding domain. In this study, we confirmed harmine-PfHsp90-specific affinity using surface plasmon resonance analysis (dissociation constant [K(d)] of 40 ?M).

Author(s): 
Shahinas, Dea
Macmullin, Gregory
Benedict, Christan
Crandall, Ian
Pillai, Dylan R.
Publication Title: 
American Journal of Physiology. Heart and Circulatory Physiology

We hypothesized that elevated partial pressures of O(2) would increase perivascular nitric oxide (*NO) synthesis. Rodents with O(2)- and.NO-specific microelectrodes implanted adjacent to the abdominal aorta were exposed to O(2) at partial pressures from 0.2 to 2.8 atmospheres absolute (ATA). Exposures to 2.0 and 2.8 ATA O(2) stimulated neuronal (type I) NO synthase (nNOS) and significantly increased steady-state.NO concentration, but the mechanism for enzyme activation differed at each partial pressure.

Author(s): 
Thom, Stephen R.
Fisher, Donald
Zhang, Jie
Bhopale, Veena M.
Ohnishi, S. Tsuyoshi
Kotake, Yashige
Ohnishi, Tomoko
Buerk, Donald G.
Publication Title: 
Blood

Most anticancer chemotherapies are immunosuppressive and induce nonimmunogenic tumor cell death. Bortezomib, a specific inhibitor of 26S proteasome, has shown clinical activity in several human tumors, including myeloma. Here we show that the uptake of human myeloma cells by dendritic cells (DCs) after tumor cell death by bortezomib, but not gamma irradiation or steroids, leads to the induction of antitumor immunity, including against primary tumor cells, without the need for any additional adjuvants.

Author(s): 
Spisek, Radek
Charalambous, Anna
Mazumder, Amitabha
Vesole, David H.
Jagannath, Sundar
Dhodapkar, Madhav V.
Publication Title: 
Clinical Chemistry

BACKGROUND: C-reactive protein (CRP) inhibits the activity of the endothelial isoform of nitric oxide synthase (eNOS) via uncoupling of the enzyme both in vitro and in vivo. eNOS activity appears to be related in part to its interaction with other cellular proteins, including heat shock protein 90 (Hsp90), caveolin-1, and porin. In this study, we examined the effect of CRP treatment of human aortic endothelial cells (HAECs) on eNOS interaction with caveolin-1, Hsp90, and porin.

Author(s): 
Valleggi, Simona
Devaraj, Sridevi
Dasu, Mohan R.
Jialal, Ishwarlal
Publication Title: 
Carcinogenesis

We have recently shown that American ginseng (AG) prevents and treats mouse colitis. Because both mice and humans with chronic colitis have a high colon cancer risk, we tested the hypothesis that AG can be used to prevent colitis-driven colon cancer. Using the azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model of ulcerative colitis, we show that AG can suppress colon cancer associated with colitis. To explore the molecular mechanisms of the anticancer effects of AG, we also carried out antibody array experiments on colon cells isolated at a precancerous stage.

Author(s): 
Cui, Xiangli
Jin, Yu
Poudyal, Deepak
Chumanevich, Alexander A.
Davis, Tia
Windust, Anthony
Hofseth, Anne
Wu, Wensong
Habiger, Joshua
Pena, Edsel
Wood, Patricia
Nagarkatti, Mitzi
Nagarkatti, Prakash S.
Hofseth, Lorne
Publication Title: 
Proteomics

Pancreatic cancer is a deadly disease characterized by poor prognosis and patient survival. Green tea polyphenols have been shown to exhibit multiple antitumor activities in various cancers, but studies on the pancreatic cancer are very limited. To identify the cellular targets of green tea action, we exposed a green tea extract (GTE) to human pancreatic ductal adenocarcinoma HPAF-II cells and performed two-dimensional gel electrophoresis of the cell lysates. We identified 32 proteins with significantly altered expression levels.

Author(s): 
Zhang, Lifeng
Pang, Eric
Loo, Rachel R. Ogorzalek
Rao, Jianyu
Go, Vay-Liang W.
Loo, Joseph A.
Lu, Qing-Yi
Publication Title: 
Molecular and Cellular Biochemistry

Cardiovascular disease (CVD) is a leading determinant of mortality and morbidity in the world. Epidemiologic studies suggest that flavonoid intake plays a role in the prevention of CVD. Consumption of cocoa products rich in flavonoids lowers blood pressure and improves endothelial function in healthy subjects as well as in subjects with vascular dysfunction such as smokers and diabetics. The vascular actions of cocoa follow the stimulation of nitric oxide (NO). These actions can be reproduced by the administration of the cocoa flavanol (-)-epicatechin (EPI).

Author(s): 
Ramirez-Sanchez, Israel
Aguilar, Hugo
Ceballos, Guillermo
Villarreal, Francisco
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Oxidative stress is a widely recognized cause of cell death associated with neurodegeneration, inflammation, and aging. Tyrosine nitration in these conditions has been reported extensively, but whether tyrosine nitration is a marker or plays a role in the cell-death processes was unknown. Here, we show that nitration of a single tyrosine residue on a small proportion of 90-kDa heat-shock protein (Hsp90), is sufficient to induce motor neuron death by the P2X7 receptor-dependent activation of the Fas pathway.

Author(s): 
Franco, Maria Clara
Ye, Yaozu
Refakis, Christian A.
Feldman, Jessica L.
Stokes, Audrey L.
Basso, Manuela
Melero Fernández de Mera, Raquel M.
Sparrow, Nicklaus A.
Calingasan, Noel Y.
Kiaei, Mahmoud
Rhoads, Timothy W.
Ma, Thong C.
Grumet, Martin
Barnes, Stephen
Beal, M. Flint
Beckman, Joseph S.
Mehl, Ryan
Estévez, Alvaro G.
Publication Title: 
PLoS genetics

The molecular chaperone Hsp90 is essential in eukaryotes, in which it facilitates the folding of developmental regulators and signal transduction proteins known as Hsp90 clients. In contrast, Hsp90 is not essential in bacteria, and a broad characterization of its molecular and organismal function is lacking. To enable such characterization, we used a genome-scale phylogenetic analysis to identify genes that co-evolve with bacterial Hsp90.

Author(s): 
Press, Maximilian O.
Li, Hui
Creanza, Nicole
Kramer, Günter
Queitsch, Christine
Sourjik, Victor
Borenstein, Elhanan
Publication Title: 
Cell Stress & Chaperones

Selection for higher production rate in cattle inhabiting challenging habitats may be considered disadvantageous because of possible deleterious effects on immunity and reproduction and, consequently, on calf crop percentage. In Israel, free-grazing high productive beef cows experience reduction in nutritional quality of forage during up to 8 months of the year.

Author(s): 
Eitam, Harel
Brosh, Arieh
Orlov, Alla
Izhaki, Ido
Shabtay, Ariel
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