Trehalose Accumulation during Cellular Stress Protects Cells and Cellular Proteins from Damage by Oxygen Radicals

Abstract

The disaccharide trehalose, which accumulates dramatically during heat shock and stationary phase in many organisms, enhances thermotolerance and reduces aggregation of denatured proteins. Here we report a new role for trehalose in protecting cells against oxygen radicals. Exposure of Saccharomyces cerevisiae to a mild heat shock (38°C) or to a proteasome inhibitor (MG132) induced trehalose accumulation and markedly increased the viability of the cells upon exposure to a free radical-generating system (H 2 O 2 /iron). When cells were returned to normal growth temperature (28°C) or MG132 was removed from the medium, the trehalose content and resistance to oxygen radicals decreased rapidly. Furthermore, a mutant unable to synthesize trehalose was much more sensitive to killing by oxygen radicals than wild-type cells. Providing trehalose exogenously enhanced the resistance of mutant cells to H 2 O 2 . Exposure of cells to H 2 O 2 caused oxidative damage to amino acids in cellular proteins, and trehalose accumulation was found to reduce such damage. After even brief exposure to H 2 O 2 , the trehalose-deficient mutant exhibited a much higher content of oxidatively damaged proteins than wild-type cells. Trehalose accumulation decreased the initial appearance of damaged proteins, presumably by acting as a free radical scavenger. Therefore, trehalose accumulation in stressed cells plays a major role in protecting cellular constituents from oxidative damage.

Dehydration-induced tps gene transcripts from an anhydrobiotic nematode contain novel spliced leaders and encode atypical GT-20 family proteins

“…An increasingly wide range of functions are attributed to trehalose; for example, it is well known to act as an organic osmolyte in micro-organisms [17,[37][38][39] and it has also been implicated in the cold stress response of E. coli [15]. Heat shock and oxidative stress do not seem to activate tps genes in A. avenae, but this contrasts with the situation in micro-organisms, where trehalose is thought to play a role [13,14,16]. At present, other than a few studies in anhydrobiosis, there is sparse information on trehalose synthesis in nematodes [40].…”

“…cerevisiae), the majority are not; accordingly, in the latter species, the role of trehalose is probably not related to desiccation tolerance. Rather, trehalose might be a general stress molecule, at least in micro-organisms, being linked to multiple stress responses, including those to heat [13,14], cold [15], reactive oxygen species [16] and elevated osmolarity [17].…”

Biochemical and genetic characterization of the pathways for trehalose metabolism in Propionibacterium freudenreichii, and their role in stress response

“…Recent studies, however, have demonstrated the ability of this disaccharide to protect cells against other types of aggressions, namely oxidative stress and heat stress. The role of trehalose as a scavenger of oxygen radicals has been shown in S. cerevisiae (Benaroudj et al, 2001). On the other hand, the accumulation of trehalose in response to elevated temperature has been reported in several mesophilic organisms, such as yeast, E. coli and Salmonella enterica (Strom & Kaasen, 1993;De Virgilio et al, 1994;Cánovas et al, 2001).…”

Successful cryopreservation of whole sheep ovary by using DMSO-free cryoprotectant

“…Subsequently, a number of studies have shown that trehalose can be used as an excellent alternative cryoprotectant in the cryopreservation of red blood and germ cells [13][14][15]. Another advantage of trehalose, as previously demonstrated, is its ability to inhibit the apoptosis level [16,17]. Because of the aforementioned advantages, trehalose has become a research hot spot in the cryopreservation field in recent years.…”