Land plants are prone to strong thermal variations and must therefore sense early moderate temperature increments to induce appropriate cellular defenses, such as molecular chaperones, in anticipation of upcoming noxious temperatures. To investigate how plants perceive mild changes in ambient temperature, we monitored in recombinant lines of the moss Physcomitrella patens the activation of a heat-inducible promoter, the integrity of a thermolabile enzyme, and the fluctuations of cytoplasmic calcium. Mild temperature increments, or isothermal treatments with membrane fluidizers or Hsp90 inhibitors, induced a heat shock response (HSR) that critically depended on a preceding Ca 2+ transient through the plasma membrane. Electrophysiological experiments revealed the presence of a Ca 2+ -permeable channel in the plasma membrane that is transiently activated by mild temperature increments or chemical perturbations of membrane fluidity. The amplitude of the Ca 2+ influx during the first minutes of a temperature stress modulated the intensity of the HSR, and Ca 2+ channel blockers prevented HSR and the onset of thermotolerance. Our data suggest that early sensing of mild temperature increments occurs at the plasma membrane of plant cells independently from cytosolic protein unfolding. The heat signal is translated into an effective HSR by way of a specific membrane-regulated Ca 2+ influx, leading to thermotolerance.

Treatment of sepsis-induced lung injury with AdHSP limits NF-kappaB activation. This results from stabilization of intermediary NF-kappaB/IkappaBalpha/IkappaB kinase complexes in a way that impairs proteasomal degradation of IkappaBalpha. This novel mechanism by which Hsp70 attenuates an intracellular process may be of therapeutic value.

Chronic exposure to environmental heat improves tolerance via heat acclimation (AC). Our previous data on mammals indicate that reprogramming the expression of genes coding for stress proteins and energy-metabolism enzymes plays a major role. Knowledge of pathways leading to AC is limited. For their identification, we established a Caenorhabditis elegans AC model and tested mutants in which signaling pathways pertinent to acclimatory responses are mutated. AC attained by maintaining adult C. elegans at 25 degrees C for 18 h enhanced heat endurance of wild-type worms subjected to heat stress (35 degrees C) and conferred protection against hypoxia and cadmium. Survival curves demonstrated that both daf-2 (insulin receptor pathway) showing enhanced heat tolerance and daf-16 loss-of-function (a transcription factor mediating DAF-2 signaling) mutants benefit from AC, suggesting that the insulin receptor pathway does not mediate AC. In contrast, the hif-1 (hypoxia inducible factor) loss-of-function strain did not show acclimation, and non-acclimated vhl-1 and egl-9 mutants (overexpressing HIF-1) had greater heat endurance than the wild type. Like mammals, HIF-1 and HSP72 levels increased in the wild-type AC nematodes. HSP72 upregulation in AC hif-1 mutants was also observed; however, it was insufficient to improve heat/stress tolerance, suggesting that HIF-1 upregulation is essential for acclimation, whereas HSP72 upregulation in the absence of HIF-1 is inadequate. We conclude that HIF-1 upregulation is both an evolutionarily conserved and a necessary component of heat acclimation. The known targets of HIF-1 imply that metabolic adaptations are essential for AC-dependent tolerance to heat and heavy metals, in addition to their known role in hypoxic adaptation.

Based on our observations of energy sparing in heat-acclimated (AC) rat hearts, we investigated whether changes in preischemic glycogen level, glycolytic rate, and plasma thyroxine level mediate cardioprotection induced in these hearts during ischemia-reperfusion insults. Control (C) (24 degrees C), AC (34 degrees C, 30 days), acclimated-euthyroid (34 degrees C + 3 ng/ml l-thyroxine), and control hypothyroid (24 degrees C + 0.02% 6-n-propyl-2-thiouracil) groups were studied. Preischemic glycogen was higher in AC than in C hearts [39.0 +/- 8.5 vs. 19.2 +/- 4.2 (SE) micromol glucose/g wet wt; P < 0.0006], and the lactate produced vs. glycogen level during total ischemia ((13)C-NMR spectroscopy) was markedly slower (AC: -0.82x, r = 0.98 vs. C: -4.7x, r = 0.9). Time to onset of ischemic contracture was lengthened, and the fraction of hearts experiencing ischemic contracture was lowered. Pulse pressure recovery was improved in AC compared with C animals before, but not after, absolute sodium iodoacetate-induced glycolysis inhibition. Acclimated-euthyroid hearts exhibited decreased ischemic tolerance, whereas induced hypothyroidism in C improved cardiotolerance. Thus higher preischemic glycogen and slowed glycolysis are associated with hypothyroidism and are likely important mediators of the improved ischemic tolerance exhibited by AC hearts.