RESUMO
Cellular proteostasis requires a network of molecular chaperones and co-chaperones, which facilitate the correct folding and assembly of other proteins, or the degradation of proteins misfolded beyond repair. The function of the major chaperones, heat shock protein 70 (Hsp70) and heat shock protein 90 (Hsp90), is regulated by a cohort of co-chaperone proteins. The J domain protein (JDP) family is one of the most diverse co-chaperone families, playing an important role in functionalizing the Hsp70 chaperone system to form a powerful protein quality control network. The intracellular malaria parasite, Plasmodium falciparum, has evolved the capacity to invade and reboot mature human erythrocytes, turning them into a vehicles of pathology. This process appears to involve the harnessing of both the human and parasite chaperone machineries. It is well known that malaria parasite-infected erythrocytes are highly enriched in functional human Hsp70 (HsHsp70) and Hsp90 (HsHsp90), while recent proteomics studies have provided evidence that human JDPs (HsJDPs) may also be enriched, but at lower levels. Interestingly, P. falciparum JDPs (PfJDPs) are the most prominent and diverse family of proteins exported into the infected erythrocyte cytosol. We hypothesize that the exported PfJPDs may be an evolutionary consequence of the need to boost chaperone power for specific protein folding pathways that enable both survival and pathogenesis of the malaria parasite. The evidence suggests that there is an intricate network of PfJDP interactions with the exported malarial Hsp70 (PfHsp70-x) and HsHsp70, which appear to be important for the trafficking of key malarial virulence factors, and the proteostasis of protein complexes of human and parasite proteins associated with pathology. This review will critically evaluate the current understanding of the role of exported PfJDPs in pathological exploitation of the proteostasis machinery by fine-tuning the chaperone properties of both human and malarial Hsp70s.
RESUMO
BACKGROUND: Transhiatal esophagectomy (THE) is a common operative procedure for carcinoma esophagus. Complications of this procedure include arrhythmias and hypotension during blunt dissection of the esophagus from posterior mediastinum. In the literature, exact incidence and type of arrhythmias have not been reported. We employed Holter monitoring during mediastinal manipulation in patients undergoing THE, for this purpose. METHODS: This prospective study was carried out in 20 consecutive American Society of Anesthesiologists grade I-II patients undergoing THE. Anesthetic technique included induction with thiopentone and maintenance with morphine, vecuronium, and isoflurane. In addition to routine parameters, Holter monitoring was undertaken to record the exact incidence and types of arrhythmias. "Premanipulation" or control period included duration of 30 minutes preceding mediastinal manipulation, while "during manipulation" or study period included the duration of mediastinal manipulation. The incidence of arrhythmias was studied for 48 hours in the postoperative period. The Fisher exact test was applied to analyze incidence of arrhythmias and hypotension. RESULTS: Out of 20 patients, only 2 had arrhythmias in the premanipulation period, while 13 had arrhythmias during the manipulation period (p < 0.01). During the manipulation period, arrhythmias included supraventricular ectopics and ventricular ectopics in 2 patients each and a combination of both in 9 patients. Arrhythmias were transient and had no correlation with either duration or degree of hypotension in all the patients. However, there was a linear relationship between hypotension and duration of mediastinal manipulation. Two patients (10%) had atrial arrhythmias in the postoperative period. CONCLUSIONS: In transhiatal esophagectomy, there is a significant incidence of both arrhythmias and hypotension during mediastinal manipulation. The incidence of arrhythmias can be minimized by limiting the duration of the manipulation. The incidence of postoperative arrhythmias was not significant.