Mild heat stress stimulates 20S proteasome and its 11S activator in human fibroblasts undergoing aging in vitro

Abstract

Repeated mild heat shock (RMHS) has been shown to have several beneficial hormetic effects on human skin fibroblast undergoing aging in vitro. Because an age-related decline in proteasome activity is 1 of the reasons for the accumulation of abnormal proteins during aging, we have investigated the effects of RMHS on the 20S proteasome, which is the major proteolytic system involved in the removal of abnormal and oxidatively damaged proteins. Serially passaged human skin fibroblasts exposed to RMHS at 41 degrees C for 60 minutes twice a week had increased 3 proteasomal activities by 40% to 95% in early- and midpassage cultures. RMHS-treated cells also contained a 2-fold higher amount of the proteasome activator 11S, and the extent of the bound activator was double in early- and midpassage cells only. Furthermore, there was no difference in the content of the 19S proteasome regulator in the stressed and the unstressed cells. Therefore, RMHS-induced proteasome stimulation in early- and midpassage fibroblasts appears to be due to an induction and enhanced binding of 11S proteasome activators. In contrast to this, the proteasomal system in late-passage senescent cells appears to be less responsive to the stimulatory effects of mild heat shock.

The age- and sex-specific decline of the 20s proteasome and the Nrf2/CncC signal transduction pathway in adaption and resistance to oxidative stress in Drosophila melanogaster

“…Such protective adaptive responses are by nature short-lived, and disappear within hours. Studies in mammalian cell culture have demonstrated the adaptive increase of the 20S proteasome, following exposure to signaling events (including H 2 O 2 , heat shock, and nutrient starvation) [51, 71]. More importantly, adaptation is found to be conserved in higher organisms, including C. elegans and D. melanogaster , where exposure to short-term H 2 O 2 , mild heat shock, 100% oxygen or irradiation, have been found to increase survival [43, 44, 53, 72-74] against serious stresses.…”

Aging and dietary restriction alter proteasome biogenesis and composition in the brain and liver

“…It may be possible for example that changes in composition arise as the result of proteasome subunits altering their expression in response to stressors. For example, it has been reported that cells tries to increase the levels of 11S during some oxidative stress conditions (Beedholm et al, 2004). Similarly, studies from our laboratory have demonstrated that oxidative stressors increase the expression of inducible proteasome subunits in neural cells (Ding et al, 2003).…”

Late-Onset Alzheimer's Disease, Heating up and Foxed by Several Proteins: Pathomolecular Effects of the Aging Process

“…Oxidative stress had no effect on proteasome expression in liver epithelial cells [108] but did increase expression of proteasome subunits in neuroblastoma cells [87]. Repeated, mild heat shock resulted in significant upregulation of proteasomal catalytic activities and 11S subunit levels in human fibroblasts [118], but acute, mild heat shock led to decreased proteasome messenger RNA (mRNA) levels, inhibition of proteasome complex assembly, decrease in chymotrypsin-like activity, and reorganization of the intracellular distribution of proteasomes [119]. Overexpressing a constitutively active form of HSF1 in mouse embryonic fibroblasts (MEF) did not increase the level of proteasomal proteins expression or proteasomal activity [120].…”