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191.
Deepa Indira Shankara Narayanan Varadarajan Santhik Subhasingh Lupitha Asha Lekshmi Krupa Ann Mathew Aneesh Chandrasekharan Prakash Rajappan Pillai Ishaque Pulikkal Kadamberi Indu Ramachandran Hari Sekar Anurup Kochucherukkan Gopalakrishnan Santhoshkumar TR 《European journal of cell biology》2018,97(1):1-14
The selective autophagic removal of mitochondria called mitophagy is an essential physiological signaling for clearing damaged mitochondria and thus maintains the functional integrity of mitochondria and cells. Defective mitophagy is implicated in several diseases, placing mitophagy as a target for drug development. The identification of key regulators of mitophagy as well as chemical modulators of mitophagy requires sensitive and reliable quantitative approaches. Since mitophagy is a rapidly progressing event and sub-microscopic in nature, live cell image-based detection tools with high spatial and temporal resolution is preferred over end-stage assays. We describe two approaches for measuring mitophagy in mammalian cells using stable cells expressing EGFP-LC3 – Mito-DsRed to mark early phase of mitophagy and Mitochondria-EGFP – LAMP1-RFP stable cells for late events of mitophagy. Both the assays showed good spatial and temporal resolution in wide-field, confocal and super-resolution microscopy with high-throughput adaptable capability. A limited compound screening allowed us to identify a few new mitophagy inducers. Compared to the current mitophagy tools, mito-Keima or mito-QC, the assay described here determines the direct delivery of mitochondrial components to the lysosome in real time mode with accurate quantification if monoclonal cells expressing a homogenous level of both probes are established. Since the assay described here employs real-time imaging approach in a high-throughput mode, the platform can be used both for siRNA screening or compound screening to identify key regulators of mitophagy at decisive stages. 相似文献
192.
193.
The paper describes the morphology and reproduction of a new species of Symphyonemopsis viz. S. pantii n. sp. isolated from enrichment cultures of a soil sample collected from the campus of Sangeet Samiti, Allahabad (India). Thalli grow as dark blue-green, small, wooly patches on soil surface but as cushion-like growths on agar plates. It has a prostrate and erect system. The latter bears secondary branches of almost equal breadth. It possesses both false and true branches. Usually true branches are reverse V-shaped. The alga shows formation of hormocysts and akinetes. In old cultures usually the main filament becomes multiseriate. The crescent-shaped stages of hormocysts are also present here. Cells of the present alga are constricted at the cross-walls On comparison it was found to come close to Symphyonemopsis katniensis Tiwari et Mitra but differs in certain fundamental characters. It is, therefore, described as a new species viz. S. pantii n. sp. (Cyanophyta, Stigonematales, Mastigocladaceae). 相似文献
194.
Asha?Negi Harminder?Pal?Singh Daizy?R.?BatishEmail author Ravinder?K.?Kohli 《Acta Physiologiae Plantarum》2014,36(4):923-929
Nickel (Ni) is a trace element essential for the growth and development of plants. Conversely, when in excess, Ni inhibits seed germination and reduces seedling growth. Therefore, we investigated the effect of Ni+2 (5–50 μM; supplied as nickel sulfate: NiSO4·6H2O) on the activity of enzymes involved in sugar metabolism of wheat (Triticum aestivum L.) seedlings after 96 h of exposure to the metal. Ni+2 treatment reduced root and coleoptile length of emerging wheat seedlings and the effect was more pronounced on the root length. Ni+2 (5–50 μM) treatment significantly enhanced carbohydrate content by 21–100 % over that of the control. In contrast, protein and reducing sugar contents declined by 17–43 and 22–69 %, respectively. The reduction in total protein content was confirmed by SDS-PAGE analysis. The activities of starch-metabolizing enzymes declined upon Ni+2 stress in a concentration-dependent manner. Activities of α- and β-amylases, acid and alkaline invertases, acid and alkaline phosphatases, and starch phosphorylase declined by 18–74 and 24–85 %, 42–76 and 21–73 %, 15–54 and 28–72 %, and 50–83 %, respectively, when compared to the control. The study concludes that Ni+2 impairs sugar metabolism as indicated by decline in the activity of sucrose and starch hydrolyzing enzymes. It resulted in decrease in the availability of biochemical energy and sugars required for the synthesis, leading to inhibition of radicle growth in germinating wheat seeds. 相似文献
195.
Shovanlal Gayen Asha M. Balakrishna Gerhard Grüber 《Journal of bioenergetics and biomembranes》2009,41(4):343-348
The N-termini of E and H of A1AO ATP synthase have been shown to interact and an NMR structure of N-terminal H1–47 has been solved recently. In order to understand the E-H assembly and the N-terminal structure of E, the truncated construct E1–52 of Methanocaldococcus jannaschii A1AO ATP synthase was produced, purified and the solution structure of E1–52 was determined by NMR spectroscopy. The protein is 60.5 Å in length and forms an α helix between the residues 8–48. The molecule is amphipathic with a strip of hydrophobic residues, discussed as a possible helix-helix interaction with neighboring subunit H. 相似文献
196.
Asha Rani Anil Sharma Raman Rajagopal Tridibesh Adak Raj K Bhatnagar 《BMC microbiology》2009,9(1):96-22
Background
Mosquitoes are intermediate hosts for numerous disease causing organisms. Vector control is one of the most investigated strategy for the suppression of mosquito-borne diseases. Anopheles stephensi is one of the vectors of malaria parasite Plasmodium vivax. The parasite undergoes major developmental and maturation steps within the mosquito midgut and little is known about Anopheles-associated midgut microbiota. Identification and characterization of the mosquito midgut flora is likely to contribute towards better understanding of mosquito biology including longevity, reproduction and mosquito-pathogen interactions that are important to evolve strategies for vector control mechanisms. 相似文献197.
Hong Zheng Hua He Ying Luo Asha Multani Phillip B Carpenter Sandy Chang 《The EMBO journal》2010,29(15):2598-2610
Repair of DNA double‐stranded breaks (DSBs) is crucial for the maintenance of genome stability. DSBs are repaired by either error prone non‐homologous end‐joining (NHEJ) or error‐free homologous recombination. NHEJ precedes either by a classic, Lig4‐dependent process (C‐NHEJ) or an alternative, Lig4‐independent one (A‐NHEJ). Dysfunctional telomeres arising either through natural attrition due to telomerase deficiency or by removal of telomere‐binding proteins are recognized as DSBs. In this report, we studied which end‐joining pathways are required to join dysfunctional telomeres. In agreement with earlier studies, depletion of Trf2 resulted in end‐to‐end chromosome fusions mediated by the C‐NHEJ pathway. In contrast, removal of Tpp1–Pot1a/b initiated robust chromosome fusions that are mediated by A‐NHEJ. C‐NHEJ is also dispensable for the fusion of naturally shortened telomeres. Our results reveal that telomeres engage distinct DNA repair pathways depending on how they are rendered dysfunctional, and that A‐NHEJ is a major pathway to process dysfunctional telomeres. 相似文献
198.
Asha Manikkoth Balakrishna Malathy Sony Subramanian Manimekalai Cornelia Hunke Shovanlal Gayen Manfred Rössle Jeyaraman Jeyakanthan Gerhard Grüber 《Journal of bioenergetics and biomembranes》2010,42(4):311-320
The structure of the C-terminus of subunit E (E101–206) of Methanocaldococcus jannaschii A-ATP synthase was determined at 4.1 Å. E101–206 consist of a N-terminal globular domain with three α-helices and four antiparallel β-strands and an α-helix at the very C-terminus. Comparison of M. jannaschii E101–206 with the C-terminus E81–198 subunit E from Pyrococcus horikoshii OT3 revealed that the kink in the C-terminal α-helix of E81–198, involved in dimer formation, is absent in M. jannaschii E101–206. Whereas a major dimeric surface interface is present between the P. horikoshii E81–198 molecules in the asymmetric unit, no such interaction could be found in the M. jannaschii E101–206 molecules. To verify the oligomeric behaviour, the low resolution structure of the recombinant E85–206 from M. jannaschii was determined using small angle X-ray scattering. Rigid body modeling of two copies of one of the monomer established a fit with a tail to tail arrangement. 相似文献
199.
Ishfaq Ahmed Sheikh Amit Kumar Singh Nagendra Singh Mau Sinha S. Baskar Singh Asha Bhushan Punit Kaur Alagiri Srinivasan Sujata Sharma Tej P. Singh 《The Journal of biological chemistry》2009,284(22):14849-14856
The crystal structure of the complex of lactoperoxidase (LPO) with its
physiological substrate thiocyanate (SCN–) has been
determined at 2.4Å resolution. It revealed that the
SCN– ion is bound to LPO in the distal heme cavity. The
observed orientation of the SCN– ion shows that the sulfur
atom is closer to the heme iron than the nitrogen atom. The nitrogen atom of
SCN– forms a hydrogen bond with a water (Wat) molecule at
position 6′. This water molecule is stabilized by two hydrogen bonds
with Gln423 Nε2 and Phe422 oxygen. In
contrast, the placement of the SCN– ion in the structure of
myeloperoxidase (MPO) occurs with an opposite orientation, in which the
nitrogen atom is closer to the heme iron than the sulfur atom. The site
corresponding to the positions of Gln423, Phe422 oxygen,
and Wat6′ in LPO is occupied primarily by the side chain of
Phe407 in MPO due to an entirely different conformation of the loop
corresponding to the segment Arg418–Phe431 of LPO.
This arrangement in MPO does not favor a similar orientation of the
SCN– ion. The orientation of the catalytic product
OSCN– as reported in the structure of
LPO·OSCN– is similar to the orientation of
SCN– in the structure of LPO·SCN–.
Similarly, in the structure of
LPO·SCN–·CN–, in which
CN– binds at Wat1, the position and orientation of
the SCN– ion are also identical to that observed in the
structure of LPO·SCN.Lactoperoxidase
(LPO4; EC 1.11.1.7) is
a Fe3+ heme enzyme that belongs to the mammalian peroxidase family
(1). The family of mammalian
peroxidases comprises lactoperoxidase
(2), eosinophil peroxidase
(3), thyroid peroxidase
(4), and myeloperoxidase (MPO)
(5). LPO, eosinophil
peroxidase, and MPO are responsible for antimicrobial function and innate
immune responses
(6–8),
whereas thyroid peroxidase plays a key role in thyroid hormone biosynthesis
(9). These peroxidases are
different from plant and fungal peroxidases because unlike plant and fungal
enzymes, the prosthetic heme group in mammalian peroxidases is covalently
linked to the protein (10).
There are also several striking structural and functional differences among
the mammalian peroxidases
(11). The heme group in MPO is
attached to the protein via three covalent linkages
(12), whereas LPO
(12,
13), eosinophil peroxidase
(12), and thyroid peroxidase
(12) contain only two ester
linkages. These covalent and various non-covalent linkages contribute
differentially to the high stability of the heme core as well as for the
peculiar values of their redox potentials
(2,
14). Furthermore, MPO consists
of two disulfide-linked protein chains, whereas LPO, eosinophil peroxidase,
and thyroid peroxidase are single chain proteins, although their chain lengths
differ greatly. In addition, their sequences contain several critical amino
acid differences that may also contribute to the variations in the
stereochemical environments of the substrate-binding sites. As a consequence
of these differences, the mammalian enzymes oxidize various inorganic ions
such as SCN–, Br–, Cl–, and
I– with differing specificities and potencies. Biochemical
studies have shown that LPO catalyzes preferentially the conversion of
SCN– to OSCN–
(15,
16), whereas MPO uses halides
(17,
18) with a preference for
chloride ion as the substrate. The preferences of eosinophil peroxidase and
thyroid peroxidase are bromide and iodide, respectively. However, the
stereochemical basis of the reported preferences for the substrates by
mammalian heme peroxidases is still unclear. So far, the structures of only
two mammalian enzymes, MPO and LPO, have been determined
(12,
13). It is of considerable
importance to identify the structural parameters that are responsible for the
subtle specificities. In the present work, we have attempted to address this
question through the new crystal structures of LPO complexes with
SCN– ions using goat, bovine, and buffalo lactoperoxidases.
Because the overall structures of complexes of SCN– with LPO
from all three species were found to be identical, the structure of the
complex of buffalo LPO with SCN– and the ternary complex with
SCN– and CN– will be discussed here, and
buffalo LPO will be termed hereafter as LPO. To highlight the factors
pertaining to binding specificity of SCN–, a comparison of
the structures of LPO·SCN– and
MPO·SCN– has also been made, revealing many valuable
differences pertaining to the observed orientations of the common substrate,
SCN– ion, when bound at the substrate-binding site in the
distal heme cavity of the two structures. The structures of
LPO·SCN– and MPO·SCN– clearly
show that the bound SCN– ions are present in the distal heme
cavity of two enzymes with opposite orientations. In the structure of
LPO·SCN–, the sulfur atom is closer to the heme iron
than the nitrogen atom, whereas in that of MPO·SCN–,
the nitrogen atom is closer to the heme iron than the sulfur atom. As a result
of this, the interactions of the SCN– ion in the distal site
of two proteins differ drastically. Gln423, a conserved water (Wat)
molecule at position 6′, and a well aligned carbonyl oxygen of
Phe422 in the proximity of the substrate-binding site in LPO
against a protruding Phe407 in MPO seem to play the key roles in
inducing the observed orientations of SCN– ions in LPO and
MPO. The structure of LPO·SCN– has also been compared
with the structure of its ternary complex with SCN– and
CN– ions. 相似文献
200.
Allophycocyanin (APC) is the least‐studied cyanobacterial bile‐pigment invariably present within the phycobilisome core of cyanobacteria. In the present study, we describe a simple, cost‐effective, and reproducible method for the purification of APC from a local isolate, Geitlerinema sp. A28DM. The pigment was extracted from the algal biomass and precipitated with 0.25% aqueous solution of the highly aromatic cationic dye “ethodin.” The precipitated APC was then subjected to a single size‐exclusion chromatographic step using Sephadex G‐100. Pure cyanobacterial APC (C‐APC) (A652/A280 of 3.2) was obtained and characterized by its absorption spectrum with maximum at 652 nm and a shoulder at 620 nm, and by SDS‐PAGE, showing two bands with molecular masses of 15 and 17.5 kDa, corresponding to α and β subunits of the biliprotein. The final yield of C‐APC was 66% from its content in the crude extract. The procedure appears to be promising for wider applications and larger production of APC. 相似文献