Sci. Aging Knowl. Environ., 24 March 2004
Preheating Primes Pruners
Gentle warming charges up protein-chopping system in human skin cells
Volunteers fill sandbags while storm clouds are brewing so the sacks will be ready when floodwaters rush in. Similarly, skin cells prepare for a flood of molten proteins by reinforcing a protein-chopping system, according to new research. This boost might explain how cells and organisms protect themselves from severe stress.
A variety of organisms appear to benefit from mild stress, a phenomenon called hormesis (see "Stress for Success"). For example, cells and organisms that have been warmed up rebound better when later broiled than do those that haven't been prewarmed. No one knows how hormesis works, but low heat might activate mechanisms that repair or purge mangled molecules, gearing them up to protect a cell from the accumulation of such debris after a roasting. For example, mild heat might activate proteasomes, molecular machines that grab damaged proteins and either send them to an acid bath or chop them up. In high heat, cells can crank up the number of proteasomes, but no one knew what happens with slight warming.
To investigate that question, Beedholm and colleagues warmed up cultured skin cells for an hour twice a week. Biochemical experiments showed that warmed and unwarmed cells carried the same quantities of the main proteasome component, 20S, and of a removable component, 19S, which focuses 20S on proteins destined for the acid bath. But slight tepidity doubled amounts of the 11S attachment, which spurs the 20S portion to chop up disfigured proteins. And twice as much 11S stuck to 20S proteasomes from heat-treated cells as from untreated cultures. Together, the results suggest that preheating primes proteasomes for chopping by providing more usable 11S.
Proteasomes from old people don't work as well as those from young people do, and the researchers wondered whether mild heating would revive proteasomes in cells that had aged in culture. The team assessed proteasome activity in cultured skin cells, which have a finite life span. As expected, proteasomes from middle-aged and old cells had diminished chopping ability. But prewarming the cells partially restored spunkiness to proteasomes from middle-aged cells; they had 28% to 100% more clipping power than did those from cells of the same age that did not get warmed. Young cells' proteasomes benefited similarly. Near the end of life, however, warming didn't enhance cutting. The results indicate that mild heat stimulates the protein-slicing abilities of the proteasome in all but the most ancient cells, which no one had noted before.
"The paper suggests a mechanism for hormesis," says geneticist Anders Olsen of the Buck Institute for Age Research in Novato, California: Prewarming boosts quantities of 11S, which prepares the proteasome to dispose of potentially destructive protein gobs. The result suggests why heated cells that have been prewarmed contain less aggregated protein than do heated cells that started cold, he adds. The primed proteasome can sack the gooey proteins as soon as heat melts them and prevent a torrent of disfigured proteins.
March 24, 2004
Science of Aging Knowledge Environment. ISSN 1539-6150