Human phospholipid scramblases (hPLSCRs) are a family of four homologous single pass transmembrane proteins (hPLSCR1-4) initially identified as the proteins responsible for Ca mediated bidirectional phospholipid translocation in plasma membrane. Though in-vitro assays had provided evidence, the role of hPLSCRs in phospholipid translocation is still debated. Recent reports revealed a new class of proteins, TMEM16 and Xkr8 to exhibit scramblase activity challenging the function of hPLSCRs. Apart from phospholipid scrambling, numerous reports have emphasized the multifunctional roles of hPLSCRs in key cellular processes including tumorigenesis, antiviral defense, protein and DNA interactions, transcriptional regulation and apoptosis. In this review, the role of hPLSCRs in mediating cell death through phosphatidylserine exposure, interaction with death receptors, cardiolipin exposure, heavy metal and radiation induced apoptosis and pathological apoptosis followed by their involvement in cancer cells are discussed. This review aims to connect the multifunctional characteristics of hPLSCRs to their decisive involvement in apoptotic pathways.
Human phospholipid scramblase 3 (hPLSCR3) is a single pass transmembrane protein that plays a vital role in fat metabolism, mitochondrial function, structure, maintenance and apoptosis. The mechanism of action of scramblases remains still unknown, and the role of scramblases in phospholipid translocation is heavily debated. hPLSCR3 is the only member of scramblase family localized to mitochondria and is involved in cardiolipin translocation at the mitochondrial membrane. Direct biochemical evidence of phospholipid translocation by hPLSCR3 is yet to be reported. Functional assay in synthetic proteoliposomes upon Ca2+ and Mg2+ revealed that, apart from cardiolipin, recombinant hPLSCR3 translocates aminophospholipids such as NBD-PE and NBD-PS but not neutral phospholipids. Point mutation in hPLSCR3 (F258V) resulted in decreased Ca2+ binding affinity. Functional assay with F258V-hPLSCR3 led to ~50% loss in scramblase activity in the presence of Ca2+ and Mg2+. Metal ion-induced conformational changes were monitored by intrinsic tryptophan fluorescence, circular dichroism, surface hydrophobicity changes and aggregation studies. Our results revealed that Ca2+ and Mg2+ bind to hPLSCR3 and trigger conformational changes mediated by aggregation. In summary, we suggest that the metal ion-induced conformational change and the aggregation of the protein are essential for the phospholipid translocation by hPLSCR3.
In this study, silver oxide nanoparticles (Ag 2 O-NPs) were synthesized from silver nitrate using green amaranth leaf extract as reducing agent. The degradation of caffeine and inactivation of Escherichia coli by Ag 2 O-NPs was studied under compact uorescent lamp illumination irradiation. Apart from that, the antibacterial and antioxidant activities of Ag 2 O-NPs were also examined. Synthesized Ag 2 O-NPs were shaped like monodispersed husk, and cubic structured with surface area and average particle size was detected to be 100.21 (m 2 /g) and 81 nm respectively. Antioxidant e cacy of the Ag 2 O-NPs was evaluated using 1, 1-diphenyl-2-picrylhydrazyl and 91% inhibition was achieved with 100 µg Ag 2 O-NPs.Bacteriocidic propensity of Ag 2 O-NPs was examined against the S. aureus and P. aeruginosa by disc diffusion, minimum inhibitory concentration (MIC), Live and dead assay. It was observed that the NPs have higher bactericidal effect on Gram-negative as compared to Gram-positive bacteria. Up to 96% photocatalytic inactivation of E. coli was achieved using 30 µg/mL of NPs, Photocatalytic degradation of caffeine (50 ppm initial concentration) was observed to be 99% at pH 9 in 15 h using 50 mg/L of Ag 2 O NPs. These results indicate that Ag 2 O NPs can be employed in environmental applications like harmful bacteria inactivation and organic pollutants degradation.
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