scholarly journals LC3 subfamily in cardiolipin-mediated mitophagy: A comparison of the LC3A, LC3B and LC3C homologs

2020 ◽  
Author(s):  
Marina N. Iriondo ◽  
Asier Etxaniz ◽  
Yaiza R. Varela ◽  
Javier H. Hervás ◽  
L. Ruth Montes ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Mitochondrial Membrane ◽  
Family Members ◽  
Terminal Region ◽  
Model Membranes ◽  
The Other ◽  
Outer Mitochondrial Membrane ◽  
Present Contribution

ABSTRACTAmong the described indicators of mitochondrial damage, externalization of the phospholipid cardiolipin (CL) to the outer mitochondrial membrane has been proposed to trigger mitophagy, acting as a signal for binding the autophagy protein LC3B. However, the behavior of the other LC3 subfamily members has not been explored yet. In the present contribution, a comparative analysis of the interaction of LC3B, LC3A and LC3C with CL-containing model membranes, as well as their ability to translocate to mitochondria was assessed. Binding of LC3A to CL was higher than that of LC3B, and both proteins showed a similar ability to colocalize with mitochondria upon induction of CL externalization by rotenone in HeLa-NDPK-D or SH-SY5Y cells. Two residues located in the N-terminal region of LC3A were shown to be important for its recognition of damaged mitochondria. Moreover, the in vitro results suggested a possible role of LC3A, but not of LC3B, in oxidized-CL recognition as a counterweight to excessive apoptosis activation. In the case of LC3C, even if this protein showed a higher binding than LC3B or LC3A to CL, binding was less specific, and colocalization of LC3C with mitochondria was not rotenonedependent. These results suggest that, at variance with LC3A, LC3C does not participate in the rotenone-CL mitophagy mechanism. The data support the notion that the various LC3/GABARAP family members might play different roles during autophagy initiation, identifying LC3A as a novel stakeholder in CL-mediated mitophagy.

Bcl-2 Family of Proteins: Life-or-Death Switch in Mitochondria

2002 ◽  
Vol 22 (1) ◽  
pp. 47-58 ◽  
Author(s):  
Yoshihide Tsujimoto
Keyword(s):  
Cell Death ◽  
Mitochondrial Membrane ◽  
Apoptotic Cell ◽  
Regulatory Protein ◽  
Family Members ◽  
Anion Channel ◽  
Permeability Transition ◽  
Outer Mitochondrial Membrane ◽  
Voltage Dependent Anion Channel ◽  
Membrane Barrier

An increase in the permeability of outer mitochondrial membrane is central to apoptotic cell death, and results in the release of several apoptogenic factors such as cytochrome c into the cytoplasm to activate downstream destructive programs. The voltage-dependent anion channel (VDAC or mitochondrial porin) plays an essential role in disrupting the mitochondrial membrane barrier and is regulated directly by members of the Bcl-2 family proteins. Anti-apoptotic Bcl-2 family members interact with and close the VDAC, whereas some, but not all, proapoptotic members interact with VDAC to open protein-conducting pore through which apoptogenic factors pass. Although the VDAC is involved directly in breaking the mitochondrial membrane barrier and is a known component of the permeability transition pore complex, VDAC-dependent increase in outer membrane permeability can be independent of the permeability transition event such as mitochondrial swelling followed by rupture of the outer mitochondrial membrane. VDAC interacts not only with Bcl-2 family members but also with proteins such as gelsolin, an actin regulatory protein, and appears to be a convergence point for a variety of cell survival and cell death signals.

scholarly journals О двух ойратских списках «Наказа Манджушри» из коллекции Н. Д. Кичикова (по материалам Кетченеровского краеведческого музея)

2021 ◽  
Vol 14 (2) ◽  
pp. 347-363
Author(s):  
Delyash N. Muzraevа ◽  
Keyword(s):  
Comparative Analysis ◽  
20Th Century ◽  
Local History ◽  
The Other ◽  
Religious Texts ◽  
Buddhist Monk ◽  
Monastic Community ◽  
History Of

Introduction. The written heritage of Kalmyk Buddhist priests, their daily practices, liturgical repertoire still remain a poorly studied page in the history of Buddhism among Mongolic peoples in the 20th century. The survived collections, clusters of religious texts prove instrumental in revealing most interesting aspects of their activities, efforts aimed at preservation of Buddhist teachings, their popularization and dissemination among believers. Goals. The paper examines two Oirat copies of the Precepts of the Omniscient [Manjushri] from N. D. Kichikov’s collection, transliterates and translates the original texts, provides a comparative analysis, and notes differences therein that had resulted from the scribe’s work, thereby introducing the narratives into scientific circulation. Materials. The article describes two Oirat manuscripts bound in the form of a notebook and contained in different bundles/collections of Buddhist religious texts stored at Ketchenery Museum of Local History and Lore. As is known, the collection is largely compiled from texts that belonged to the famous Kalmyk Buddhist monk Namka (N. D. Kichikov). Results. The analysis of the two Oirat texts with identical titles — Precepts of the Omniscient [Manjushri] — shows that their contents coincide generally but both the texts contain fragmented omissions (separate words, one or several sentences) that are present in the other. At the same time, when omitting fragments of the text addressed to the monastic community, the scribe was obviously guided by that those would be superfluous for the laity. Thus, our comparative analysis of the two manuscript copies demonstrates the sometimes dramatic role of the scribe in transmitting Buddhist teachings.

scholarly journals KLF7: a new candidate biomarker and therapeutic target for high-grade serous ovarian cancer

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Marta De Donato ◽  
Gabriele Babini ◽  
Simona Mozzetti ◽  
Marianna Buttarelli ◽  
Alessandra Ciucci ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Prognostic Marker ◽  
Late Stage ◽  
Therapeutic Target ◽  
Family Members ◽  
High Grade ◽  
Serous Ovarian Cancer

Abstract Background In spite of great progress in the surgical and clinical management, until now no significant improvement in overall survival of High-Grade Serous Ovarian Cancer (HGSOC) patients has been achieved. Important aspects for disease control remain unresolved, including unclear pathogenesis, high heterogeneity and relapse resistance after chemotherapy. Therefore, further research on molecular mechanisms involved in cancer progression are needed to find new targets for disease management. The Krüppel-like factors (KLFs) are a family of transcriptional regulators controlling several basic cellular processes, including proliferation, differentiation and migration. They have been shown to play a role in various cancer-relevant processes, in a context-dependent way. Methods To investigate a possible role of KLF family members as prognostic biomarkers, we carried out a bioinformatic meta-analysis of ovarian transcriptome datasets in different cohorts of late-stage HGSOC patients. In vitro cellular models of HGSOC were used for functional studies exploring the role of KLF7 in disease development and progression. Finally, molecular modelling and virtual screening were performed to identify putative KLF7 inhibitors. Results Bioinformatic analysis highlighted KLF7 as the most significant prognostic gene, among the 17 family members. Univariate and multivariate analyses identified KLF7 as an unfavourable prognostic marker for overall survival in late-stage TCGA-OV and GSE26712 HGSOC cohorts. Functional in vitro studies demonstrated that KLF7 can play a role as oncogene, driving tumour growth and dissemination. Mechanistic targets of KLF7 included genes involved in epithelial to mesenchymal transition, and in maintaining pluripotency and self-renewal characteristics of cancer stem cells. Finally, in silico analysis provided reliable information for drug-target interaction prediction. Conclusions Results from the present study provide the first evidence for an oncogenic role of KLF7 in HGSOC, suggesting it as a promising prognostic marker and therapeutic target.

THE ROLE OF ADSORPTION IN CONTROLLING THE RATE OF REACTION OF CHLORAMBUCIL WITH PROTEIN

1963 ◽  
Vol 41 (4) ◽  
pp. 931-939 ◽  
Author(s):  
J. H. Linford
Keyword(s):  
Molecular Weight ◽  
Carboxylic Acid ◽  
Bovine Serum Albumin ◽  
Inverse Relationship ◽  
Reaction Rate ◽  
The Other ◽  
Alkylation Reaction ◽  
Rate Of Reaction

Two proteins, haemoglobin and bovine serum albumin, have been studied with respect to their rates of alkylation by chlorambucil in vitro at 37 °C and pH 8.4. The proteins are of nearly the same molecular weight and free carboxylic acid content, but the alkylation reaction is 30 times faster with haemoglobin. On the other hand, the adsorption of chlorambucil by albumin is 20 times greater than that exhibited by haemoglobin. This inverse relationship between extent of adsorption and reaction rate suggests that adsorption protects the chlorambucil from activation in the solvent.

Prostaglandins and renin release in vitro

1981 ◽  
Vol 240 (6) ◽  
pp. E609-E614
Author(s):  
C. S. Lin ◽  
H. Iwao ◽  
S. Puttkammer ◽  
A. M. Michelakis
Keyword(s):  
Arachidonic Acid ◽  
Renal Cortex ◽  
The Other ◽  
Renin Release ◽  
Eicosatetraenoic Acid ◽  
Juxtaglomerular Cells ◽  
Prostaglandin F2 Alpha ◽  
Prostaglandin System

The present studies were undertaken to explore further the role of prostaglandins in the release of renin from the renal cortex. To provide the best assessment of renin release, renin was determined by a radioimmunoassay for the direct measurement of renin. Slices of mouse renal cortex were incubated at 37 degrees C with arachidonic acid (AA), 5,8,11,14-eicosatetraenoic acid (ETA), indomethacin, prostaglandins, and synthetic prostaglandin endoperoxide analogue (EPA). Our results showed that AA at 1.5 X 10(-8) M significantly increased renin release at 10 and 30 min of incubation. This renin increase ws abolished by either ETA or indomethacin. Prostaglandin F2 alpha (PGF2 alpha) also significantly stimulated renin release at 10 and 60 min. PGE2 and 16,16-dimethyl PGE2 (DMPGE2) showed much less renin release-stimulating activity. EPA and PGI2 on the other hand very strongly stimulated renin release. However, at higher concentrations the stimulating effect of PGI2 and EPA disappeared and even became inhibitory in the case of EPA. Other prostaglandins were found to have no effect on renin release. The results suggest that the prostaglandin system directly affects renin release from the juxtaglomerular cells independent of systemic neurogenic and hemodynamic influences.

scholarly journals Non-Soviet Perspectives on the Great Famine: A Comparative Analysis of British, Italian, Polish, and German Sources

2019 ◽  
Vol 48 (3) ◽  
pp. 444-459 ◽  
Author(s):  
Paolo Fonzi
Keyword(s):  
Comparative Analysis ◽  
Soviet Union ◽  
Diplomatic Relations ◽  
Present Contribution ◽  
Soviet Government ◽  
Great Famine ◽  
The Soviet Union ◽  
Key Issues ◽  
The Relationship

AbstractThe present contribution analyzes systematically diplomatic reports written by German, Italian, British, and Polish representatives in the Soviet Union at the time of the Great Famine. Based on both published documents and unpublished archival sources, the article examines comparatively the perception of the Great Famine in these four countries. After providing a short overview of the diplomatic relations between the Soviet Union and the four countries at the time of the famine, this article examines how German, Italian, British, and Polish diplomats explained three key issues for understanding the Great Famine: (1) the role of the conflicts between state and peasantry in unleashing the famine; (2) the issue of whether the Soviet government intentionally caused the famine; and (3) the role of intentions in the development of the famine and the relationship between the nationalities policy of the Soviet government and the famine.

Anionic and cationic exchange mechanisms in the skin of anurans, with special reference to Leptodactylidae in vivo

1971 ◽  
Vol 262 (842) ◽  
pp. 163-174 ◽  
Keyword(s):  
Transport Mechanism ◽  
Selective Inhibition ◽  
The Other ◽  
Sodium Absorption ◽  
Experimental Conditions ◽  
Net Flux ◽  
Cationic Exchange

In several species of anurans, the in vivo skin has been shown to absorb Na + and Cl - independently from dilute external solutions. That the mechanism for sodium absorption is different from that of chloride absroption is born out by the following: (1) Either of these ions is absorbed without an accompanying ion when this latter is impermeant. (2) From NaCl solutions there can be an unequal absorption of sodium and chloride. (3) A selective inhibition of the absorption of one of the ions can be produced experimentally, while the net flux of the other remains unchanged. In all these situations, the absorbed ion has to be exchanged against an endogenous ion of the same charge. In Calyptocephalella gayi , H + and HCO - 3 are exchanged against sodium and chloride respectively. A comparison of the relationships between H + excretion and Na + absorption in vivo skins and shortcircuited in vitro skins shows that in the latter no H + excretion occurs, only the Na + transport being maintained under these experimental conditions. From this, one must conclude that the active Na + transport is the motive factor of the transport mechanism. H + excretion by the in vivo skin plays the role of physiologically short-circuiting the Na + transport.

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