Endothelial Monocyte-activating polypeptide-II Research Articles

Inhibition of apoptosis induced by ischemia-reperfusion prevents inflammation.

Ischemia followed by reperfusion leads to severe organ injury and dysfunction. Inflammation is considered to be the most important cause of tissue injury in organs subjected to ischemia. The mechanism that triggers inflammation and organ injury after ischemia remains to be elucidated, although different causes have been postulated. We investigated the role of apoptosis in the induction of inflammation and organ damage after renal ischemia. Using a murine model, we demonstrate a relationship between apoptosis and subsequent inflammation. At the time of reperfusion, administration of the antiapoptotic agents IGF-1 and ZVAD-fmk (a caspase inactivator) prevented the early onset of not only renal apoptosis, but also inflammation and tissue injury. Conversely, when the antiapoptotic agents were administered after onset of apoptosis, these protective effects were completely abrogated. The presence of apoptosis was directly correlated with posttranslational processing of the endothelial monocyte-activating polypeptide II (EMAP-II), which may explain apoptosis-induced influx and sequestration of leukocytes in the reperfused kidney. These results strongly suggest that apoptosis is a crucial event that can initiate reperfusion-induced inflammation and subsequent tissue injury. The newly described pathophysiological insights provide important opportunities to effectively prevent clinical manifestations of reperfusion injury in the kidney, and potentially in other organs.

Precursor of Pro-apoptotic Cytokine Modulates Aminoacylation Activity of tRNA Synthetase

Endothelial monocyte activating polypeptide II (EMAPII) is a cytokine that is specifically induced by apoptosis. Its precursor (pro-EMAPII) has been suggested to be identical to p43, which is associated with the multi-tRNA synthetase complex. Herein, we have demonstrated that the N-terminal domain of pro-EMAPII interacts with the N-terminal extension of human cytoplasmic arginyl-tRNA synthetase (RRS) using genetic and immunoprecipitation analyses. Aminoacylation activity of RRS was enhanced about 2.5-fold by the interaction with pro-EMAPII but not with its N- or C-terminal domains alone. The N-terminal extension of RRS was not required for enzyme activity but did mediate activity stimulation by pro-EMAPII. Pro-EMAPII reduced the apparent Km of RRS to tRNA, whereas the kcat value remained unchanged. Therefore, the precursor of EMAPII is a multi-functional protein that assists aminoacylation in normal cells and releases the functional cytokine upon apoptosis.

Cloning and sequencing of cDNA encoding the rice methionyl-tRNA synthetase.

Three overlapping clones of cDNA, Mos43, Mos28 and Mos60, coding for methionyl-tRNA synthetase were obtained by screening the Oryza sativa lambda gt11 library. Their nucleotide sequence of 2850 bp was determined. The deduced amino-acid sequence of the isolated clones contains a HLGN and KFSKS motifs, which are conserved for this family of enzymes and have been proposed to be the signature sequences for class I aminoacyl-tRNA synthetases. A comparison of the rice MetRS primary structure with those deposited in EMBL/GenBank points to its high homology to yeast, human and Caenorhabditis elegans MetRSs. Interestingly, a great similarity of its C terminus to endothelial-monocyte-activating polypeptide II (EMAPII) and yeast protein G4p1 was observed.