Furthermore, signaling through CD74 appears to mediate MIF induced activation of AMPK in the heart. Sanchez-Nino et al. have reported constitutive CD74 expression in the rat kidney, which was localized to glomeruli and tubules and increased with diabetes. Furthermore, CD74 was found to be expressed by cultured podocytes and proximal tubular cells. In the present study we found to that CD74 was detectable by Western blot of kidney lysates, but the level of expression was markedly lower than in the heart. This observation raises the possibility that the lower CD74 expression seen in the kidney compared to the heart might help explain the different effects of MIF on AMPK activity between heart and kidney. At present, however, the explanation for the difference between the regulation of AMPK by MIF between the heart and the kidney is not clear. Nonetheless, it is known that activation of AMPK in response to specific regulators can vary between different tissues. For example AMPK activity is increased by leptin in skeletal muscle and reduced by leptin in the hypothalamus. The two major pathways of AMPK activation are known to be mediated by an increase in cellular, acting via the upstream kinase LKB1, or an increase in cellular, acting via the upstream kinase CaMKKb. Whilst acute renal ischemia is known to acutely increase both cellular and, it is not known whether activation of AMPK by acute renal ischemia occurs predominantly downstream of LKB1 or CaMKKb. The present study shows, however, that the pathways of AMPK activation by acute renal ischemia involve phosphorylation of AMPK-aThr172 by upstream kinase and this is not influenced by the presence or absence of MIF. It is assumed that one or very few var genes are expressed per single parasite. Occasional transcriptional switching which occurs at rates ranging from 0.2 up to 16% then leads to the change in the expressed PfEMP-1, enabling constant immune evasion. While the purpose of PfEMP-1 is the interaction with host cell receptors leading to the retention of the infected red blood cell in the deep vasculature thus avoiding spleen passage, no clear function has so far been elucidated for proteins encoded by other multigene families. Proteins of RIFIN, STEVOR and PFM2tm families are also expressed at the infected red blood cell surface and little is known about the function of these antigens regarding malaria persistence, pathogeny and cytoadherence. The multigene rif family has approximately 160 different intact members in the 3D7 strain annotated in the PlasmoDB databank. Recently, we and others have characterized the transcriptional profile of this family, showing that i) particular, sometimes identical transcripts are expressed in different adhesive phenotypes and ii) that rif transcription switches apparently faster than transcription of var genes, at least in vitro. Similar to var genes, rif gene transcription and silencing is dependent on the histone VE-822 deacetylase PfSir2A and genome-wide chromatin immunoprecipitation experiments have shown that silent rif gene loci are associated to histone 3 lysine 9 trimethylation as are other virulence-associated multigene families. Finally, results from the laboratory of Kirk Deitsch have shown that the transcription of several variant multigene families.