Accelerated protein aggregation induced by macrophage migration inhibitory factor under heat stress conditions.
Kinetics of thermal aggregation of model protein substrates (glycogen phosphorylase b from rabbit skeletal muscle and yeast alcohol dehydrogenase) were investigated under heat stress conditions (41-48 degrees C) in the presence of macrophage migration inhibitory factor (MIF), a heat-stable hydrophobic protein (12.5 kD). Anti-chaperone MIF activity found by turbidimetry manifests itself in significantly accelerated protein aggregation and increased limiting value of apparent optical absorption at 360 nm and t --> infinity in the sub-stoichiometric range of MIF concentrations. The aggregation kinetics is shown to have cooperative character. Possible reversibility of aggregation after removal of denaturing conditions was demonstrated using alcohol dehydrogenase aggregation at a temperature close to the physiological level (41.5 degrees C). This reversibility is caused by solubility of aggregates and stabilization of oligomeric structure of the substrate as a result of MIF binding to the partially denatured protein. The data suggest that in spite of distinct anti-chaperone effect, the chaperone-like activity of MIF can be observed in the case of heat stress removal and restoration of the system to normal conditions.
Bach Institute of Biochemistry, Russian Academy of Sciences, 119071 Moscow, Russia.
O A
OA
Cherepkova
E M
EM
Lyutova
T B
TB
Eronina
B Ya
BY
Gurvits
D000426:Alcohol Dehydrogenase / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001923:Brain Chemistry; D002417:Cattle; D004591:Electrophoresis, Polyacrylamide Gel; D024982:Glycogen Phosphorylase, Muscle Form / Q000737:chemistry / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism; D006358:Hot Temperature; D007700:Kinetics; D008263:Macrophage Migration-Inhibitory Factors / Q000737:chemistry* / Q000302:isolation & purification / Q000502:physiology; D018482:Muscle, Skeletal / Q000201:enzymology; D018384:Oxidative Stress; D011817:Rabbits; D012441:Saccharomyces cerevisiae / Q000201:enzymology
D006360:Heat-Shock Proteins; D008263:Macrophage Migration-Inhibitory Factors; D000426:Alcohol Dehydrogenase; D024982:Glycogen Phosphorylase, Muscle Form