Dual targeting of heat shock proteins 90 and 70 promotes cell death and enhances the anticancer effect of chemotherapeutic agents in bladder cancer

AbstractChanges in the viability, infectivity and heat shock protein (Hsp) levels are reported in Trichinella spiralis first stage larvae (L1) stored in 199 medium for up to seven days at 37°C. These conditions induce stress that the larvae, eventually, cannot overcome. After three days of storage, the infectivity and viability were unchanged, although higher Hsp70 levels were observed. After this time, larvae gradually lost viability and infectivity, coinciding with a decrease in Hsp70 and Hsp90 and an increase in actin (a housekeeping protein). In addition, a possibly inducible heat shock protein, Hsp90i, appeared as constitutive Hsp90 disappeared. No significant changes in Hsp60 levels were detected at any time. These results suggest that heat shock proteins initially try to maintain homeostasis, but on failing, may be involved in cell death.

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SECOND ANOXIA-REOXYGENATION DOES NOT CAUSE THE APOPTOTIC CELL DEATH OF NEONATAL CARDIOMYOCYTES: POSSIBLE ROLE OF CHANGES OF mRNA EXPRESSION OF CYTOPROTECTIVE GENES

Fiziolohichnyĭ zhurnal ◽

10.15407/fz55.01.019 ◽

2009 ◽

Vol 55 (1) ◽

pp. 19-26

Author(s):

O.V. Surova ◽

◽

V.E. Dosenko ◽

V.S. Nagibin ◽

L.V. Tumanovskaya ◽

...

Keyword(s):

Cell Death ◽

Heat Shock ◽

Heat Shock Proteins ◽

Apoptotic Cell ◽

First Episode ◽

Mrna Levels ◽

Neonatal Cardiomyocytes ◽

Genes Expression ◽

Shock Proteins

The cells death and genes expression in neonatal cardiomyocytes culture at two anoxia-reoxygenation modeling were investigated. The primary culture of neonatal cardiomyocytes was undergone 30 min of anoxia followed by 24 h (A-R1) and the second anoxia-reoxygenation – 30 min and 60 min respectively (A-R2). The percentages of living, necrotic, apoptotic and autophagic cells were determined by staining with bis-benzimide, propidium iodide and monodansylcadaverine. Anoxia-reoxygenation significantly influenced the ratio of living, necrotic, apoptotic and autophagic cells both at its first A-R1 and second A-R2 episodes. It was shown that the main mechanism of cell death after the both periods of anoxia-reoxygenation is necrosis. The changes of mRNA levels of genes of heat shock proteins HSP70 and HSP90, antiapoptotic protein Bcl2 and key regulator of au-tophagy FRAP in cardiomyocytes culture were established. The data obtained allow to make suggestion that in 24 h after the first episode of anoxia-reoxygenation A-R1 the overexpression of heat shock proteins starts the cascade of reactions that causes the necrotic cell death prevalent and the blocking of apoptotic program at second anoxia-reoxygenation A-R2.

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Induction of DnaK and GroEL heat shock proteins by fluoroquinolones in Escherichia coli.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.1.193 ◽

1997 ◽

Vol 41 (1) ◽

pp. 193-195 ◽

Cited By ~ 4

Author(s):

T Mizushima ◽

M Matsuo ◽

K Sekimizu

Keyword(s):

Escherichia Coli ◽

Cell Death ◽

Heat Shock ◽

Heat Shock Proteins ◽

Dna Relaxation ◽

Cellular Dna ◽

Shock Proteins ◽

Kinetics Of

Various fluoroquinolones (norfloxacin, enoxacin, ofloxacin, levofloxacin, and sparfloxacin) induce DnaK and GroEL heat shock proteins in Escherichia coli. The induction is transient, consistent with the kinetics of cellular DNA relaxation. The concentrations of fluoroquinolones required for induction are similar to those required for DNA relaxation and much higher than those required for cell death.

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HEAT SHOCK PROTEINS AS THE DRUGGABLE TARGETS IN LEISHMANIASIS: PROMISES AND PERILS

Infection and Immunity ◽

10.1128/iai.00559-20 ◽

2020 ◽

Author(s):

Pragya Prasanna ◽

Arun Upadhyay

Keyword(s):

Heat Shock ◽

Heat Shock Proteins ◽

Chemotherapeutic Agents ◽

Inflammatory Reactions ◽

Physiological Importance ◽

Cellular Processes ◽

Insect Gut ◽

Shock Proteins ◽

Drug Resistant Strains ◽

Druggable Targets

Leishmania, the causative agent of leishmaniasis, is an intracellular pathogen that thrives in the insect gut and mammalian macrophages to complete its life cycle. Apart from temperature difference (26oC to 37oC), it encounters several harsh conditions, including oxidative stress, inflammatory reactions, and low pH. Heat shock proteins (HSPs) play essential roles in cell survival by strategically reprogramming cellular processes and signaling pathways. HSPs assist cells in multiple functions, including differentiation, adaptation, virulence, and persistence in the host cell. Due to cyclical epidemiological patterns, limited chemotherapeutic options, drug resistance, and the absence of a vaccine, control of leishmaniasis remain a far-fetched dream. The essential roles of HSPs in parasitic differentiation and virulence and increased expression in drug-resistant strains highlight their importance in combating the disease. In this review, we highlighted the diverse physiological importance of HSPs present in Leishmania, emphasizing their significance in disease pathogenesis. Subsequently, we assessed the potential of HSPs as a chemotherapeutic target and underlined the challenges associated with it. Furthermore, we have summarized a few ongoing drug discovery initiatives that need to be explored further to develop clinically successful chemotherapeutic agents in the future.

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