Human hsp27, Drosophila hsp27 and human alphaB-crystallin expression-mediated increase in glutathione is essential for the protective activity of these proteins against TNFalpha-induced cell death.

Abstract

Expression of small stress proteins (shsp) enhances the survival of mammalian cells exposed to heat or oxidative injuries. Recently, we have shown that the expression of shsp from different species, such as human hsp27, Drosophila hsp27 or human alphaB‐crystallin protected murine L929 cells against cell death induced by tumor necrosis factor (TNFalpha), hydrogen peroxide or menadione. Here, we report that, in growing L929 cell lines, the presence of these shsp decreased the intracellular level of reactive oxygen species (ROS). shsp expression also abolished the burst of intracellular ROS induced by TNFalpha. Several downstream effects resulting from the TNFalpha‐mediated ROS increment, such as NF‐kappaB activation, lipid peroxidation and protein oxidation, were inhibited by shsp expression. We also report that the expression of these different shsp raised the total glutathione level in both L929 cell lines and transiently transfected NIH 3T3‐ras cells. This phenomenon was essential for the shsp‐mediated decrease in ROS and resistance against TNFalpha. Our results therefore suggest that the protective activity shared by human hsp27, Drosophila hsp27 and human alphaB‐crystallin against TNFalpha‐mediated cell death and probably other types of oxidative stress results from their conserved ability to raise the intracellular concentration of glutathione.

A potential role of heat shock proteins and nicotinamide N‐methyl transferase in predicting response to radiation in bladder cancer

“…They suggested that radioresistance is due to an effect of HSP on the glutathione redox cycle, by facilitating the reduction of oxidised glutathione (GSSG) to GSH. 15 Also, Mehlen et al 16 reported that HSP27 raised the level of intracellular glutathione in response to TNF␣ and suggested a similar effect in response to other oxidative stress. Thus, it is not unlikely that upregulation will occur in response to radiation and result in radioresistance as the case is with HSP25.…”

Effects of intrinsic aerobic capacity, aging and voluntary running on skeletal muscle sirtuins and heat shock proteins

“…HSF1 and HSF2 are important for protecting cells from protein-damaging stress associated with misfolded proteins and aging as well as aging-related diseases (Rodgers et al, 2005;. Interestingly, Hsp27 has been shown to increase the cellular anti-oxidant defense (Mehlen et al, 1996). Elevated HSF1, HSF2 and Hsp27 levels reported here may indicate that muscle cells of aged animals respond to aging-related accumulation of oxidative stress and attempt to compensate the stress by increasing the amount of components required for the protective molecular machinery (Murlasits et al, 2006).…”

“…However, in skeletal muscle, old animals seem to retain their capability to accumulate Hsp protein when subjected to heat shock . Both HSF1 and HSF2 are essential for protecting cells from protein-damaging stress associated with misfolded proteins and therefore aging (Ostling et al 2007;), whereas Hsp27 has been shown to increase the cellular anti-oxidant defense (Mehlen et al 1996). Elevated Hsp27, HSF1 and HSF2 levels reported here may indicate that muscle cells of aged HCR/LCR rats responded to aging-related accumulation of oxidative stress and attempted to compensate the stress by increasing the amount of protective molecular machinery in both of the studied rat lines (Murlasits et al 2006).…”

Hsp27 functions as a negative regulator of cytochrome c-dependent activation of procaspase-3

“…Diverse agents, such as TNFa, IL-1 and oxidative stress have been reported as potent modulators of mammalian Hsp27 phosphorylation (Arrigo and Landry, 1994). Overexpression of Hsp27 has been shown to protect cells against necrosis induced by anti-cancer drugs, TNFa or oxidative stress (Mehlen et al, 1995(Mehlen et al, , 1996a. Mammalian Hsp27 has also been shown to play a role in cell di erentiation (Shakoori et al, 1992).…”