[
Adv Exp Med Biol,
2007]
The physiological adjustment of organisms in response to temperature variation is a crucial part of coping with environmental stress. An important component of the cold response is the increase in membrane lipid unsaturation, and this has been linked to an enhanced resistance to the debilitating or lethal effects of cold. Underpinning the lipid response is the upregulation of fatty acid desaturases (des), particularly those introducing double bonds at the 9-10 position of saturated fatty acids. For plants and microbes there is good genetic evidence that regulation of des genes, and the consequent changes in lipid saturation, are causally linked to generation of a cold-tolerant phenotype. In animals, however, supporting evidence is almost entirely limited to correlations of saturation with cold conditions. We describe our recent attempts to provide a direct test of this relationship by genetic manipulation of the nematode Caenorhabditis elegans. We show that this species displays a strong cold tolerant phenotype induced by prior conditioning to cold, and that this is directly linked to upregulated des activity. However, whilst genetic disruption of des activity and lipid unsaturation significantly reduced cold tolerance, animals retained a substantial component of their stress tolerant phenotype produced by cold conditioning. This indicates that mechanisms other than lipid unsaturation play an important role in cold adaptation.
[
Immunol Rev,
1998]
This article focuses on four human carboxypeptidases (CPs): two metallo-CPs and two serine CPs. The metallo-CPs are members of the so-called B-type regulatory CP family, as they cleave only the C-terminal basic amino acids Arg or Lys. The plasma membrane-bound CPM and the mainly, but not exclusively, intracellular CPD are surveyed from this group of enzymes. These enzymes can regulate peptide hormone activity at the cell surface and possibly intracellularly after receptor-mediated endocytosis and may also participate in peptide hormone processing. The serine CPs, as their name indicates, contain a serine residue in the active center essential for catalytic activity that reacts with organophosphorus inhibitors. Prolylcarboxypeptidase (PRCP) (angiotensinase C) and deamidase (cathepsin A, lysosomal protective protein) are discussed here. These two enzymes are highly concentrated in lysosomes; however, they may also be active extracellularly after their release from lysosomes in soluble form or in a plasma membrane-bound complex. Whereas deamidase cleaves a variety of peptides with C-terminal or penultimate hydrophobic residues (e.g. substance P, angiotensin I, bradykinin, endothelin, fMet-Leu-Phe). PRCP cleaves only peptides with a penultimate Pro residue (e.g. des-Arg9-bradykinin, angiotensin II). These enzymes may also be involved in terminating signal transduction by inactivating peptide ligands after receptor endocytosis.