Cellular mechanisms of acute versus delayed preconditioning Ronald J Korthuis, Dean C Gute, Gediminas Cepinskas, Peter R Kvietys  Pathophysiology  Volume 5, Issue 1, Pages 35-48 (June 1998) DOI: 10.1016/S0928-4680(98)00007-8

Fig. 1 Mechanisms of preconditioning and delayed preconditioning. During the period of preconditioning ischemia, tissue adenosine levels rise and activate adenosine A1 and/or A3 receptors. This may increase the activity of phospholipase C (PLC) or D (PLD), events that appear to be coupled by pertussis toxin-sensitive G-proteins. Adenosine-induced activation of PLC and PLD may be accentuated by bradykinin or oxidants produced during the period of preconditioning ischemia or by activation of α1-adrenergic receptors, the net effect of which is to increase the formation of diacylglycerol (DAG) which, in turn, promotes the translocation of specific isoforms of protein kinase C (PKC) to cell membranes. Although the molecular targets for PC-induced, PKC-dependent phosphorylation are unclear, a growing body of evidence suggests that activation of tyrosine kinases, stimulation of ATP-sensitive potassium (KATP) channels, and induction of 5′-nucleotidase translocation to cell surfaces may play major roles, the relative importance of these effectors being dependent on the model that is being studied. Although not studied as extensively, the molecular signals that initiate delayed PC appear to be similar to those involved in preconditioning. However, the effector arm of delayed PC is quite different from PC in that it involves adaptational alterations in gene expression such that the expression of antioxidant enzymes, heat shock proteins and nitric oxide synthases are upregulated, effects that may involve activation of transcription factors (TF) such as NKκB. Pathophysiology 1998 5, 35-48DOI: (10.1016/S0928-4680(98)00007-8)