The ATP-dependent ClpQY protease system in Plasmodium falciparum is a prokaryotic machinery in the parasite. In the present study, we have identified the complete ClpQY system in P. falciparum and elucidated its functional importance in survival and growth of asexual stage parasites. We characterized the interaction of P. falciparum ClpQ protease (PfClpQ) and PfClpY ATPase components, and showed that a short stretch of residues at the C terminus of PfClpY has an important role in this interaction; a synthetic peptide corresponding to this region antagonizes this interaction and interferes with the functioning of this machinery in the parasite. Disruption of ClpQY function by this peptide caused hindrance in the parasite growth and maturation of asexual stages of parasites. Detailed analyses of cellular effects in these parasites showed features of apoptosis-like cell death. The peptide-treated parasites showed mitochondrial dysfunction and loss of mitochondrial membrane potential. Dysfunctioning of mitochondria initiated a cascade of reactions in parasites, including activation of VAD–FMK-binding proteases and nucleases, which resulted in apoptosis-like cell death. These results show functional importance of mitochondrial proteases in the parasite and involvement of mitochondria in programmed cell death in the malaria parasites.

Self-preserving personal care/cosmetic products can be developed which are as efficacious as preserved products by a prudent selection of multifunctional actives, antioxidants and chelators as a part of the formulation.

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Abstract:Xenobiotics are synthetic compounds foreign to the biological system. They often retain their qualities in the aquatic environment with the ability to cause oxidative stress in these organisms by activating the endogenous production of reactive oxygen species (ROS). Overloading of the estuaries with contaminants for a longer period has an impact on fish production. The grey mullet (Mugil cephalus) is capable of concentrating contaminants and is considered suitable for biomarker studies. Brain is an appropriate organ for the study of the effects of xenobiotics due to its morphological heterogeneity, metal accumulating capacity and susceptibility to histopathological damage by metals. Cells respond to stress in a variety of ways by activation of pathways that promote survival or apoptosis. Hence the present study aimed at understanding the effect of pollutants on fish brain by assessing stress markers (LHP, Trx) and signalling proteins (HIF1α, HSP70, CYP1A2 and ASK-1). The changes in the biomolecular composition was assessed using Fourier Transform Infrared Spectroscopy (FTIR). A significant increase in LHP and Trx reveals pollutant induced oxidative stress. An alteration in the functional groups of lipid and proteins were identified by FTIR. A variation in the expression of HIF1α and CYP1A2 infers xenobiotic induced stress. A significant elevation in the level of HSP 70 and insignificant increase in the level of ASK-1 depicts the prime role of HSP 70. Thus the present study concludes that upregulation of HSP70 plays a cytoprotective role during xenobiotic induced stress in fish brain.

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