scholarly journals Anti-Aggregative Effect of the Antioxidant DJ-1 on the TPPP/p25-Derived Pathological Associations of Alpha-Synuclein

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2909
Author(s):  
Judit Oláh ◽  
Attila Lehotzky ◽  
Tibor Szénási ◽  
Judit Ovádi
Keyword(s):  
Early Stage ◽  
Antioxidant Properties ◽  
Alpha Synuclein ◽  
Proteolytic Degradation ◽  
Tubulin Polymerization ◽  
Functional Protein ◽  
Microtubule Network ◽  
Fluorescence Confocal Microscopy ◽  
Intracellular Fluorescence ◽  
Tubulin Polymerization Promoting Protein

DJ-1, a multi-functional protein with antioxidant properties, protects dopaminergic neurons against Parkinson’s disease (PD). The oligomerization/assembly of alpha-synuclein (SYN), promoted by Tubulin Polymerization Promoting Protein (TPPP/p25), is fatal in the early stage of PD. The pathological assembly of SYN with TPPP/p25 inhibits their proteolytic degradation. In this work, we identified DJ-1 as a new interactive partner of TPPP/p25, and revealed its influence on the association of TPPP/p25 with SYN. DJ-1 did not affect the TPPP/p25-derived tubulin polymerization; however, it did impede the toxic assembly of TPPP/p25 with SYN. The interaction of DJ-1 with TPPP/p25 was visualized in living human cells by fluorescence confocal microscopy coupled with Bifunctional Fluorescence Complementation (BiFC). While the transfected DJ-1 displayed homogeneous intracellular distribution, the TPPP/p25-DJ-1 complex was aligned along the microtubule network. The anti-aggregative effect of DJ-1 on the pathological TPPP/p25-SYN assemblies was established by the decrease in the intensity of their intracellular fluorescence (BiFC signal) and the increase in the proteolytic degradation of SYN complexed with TPPP/p25 due to the DJ-1-derived disassembly of SYN with TPPP/p25. These data obtained with HeLa and SH-SY5Y cells revealed the protective effect of DJ-1 against toxic SYN assemblies, which assigns a new function to the antioxidant sensor DJ-1.

scholarly journals The effect of metabolism on the course of labor and the postpartum period in highly productive cows

2020 ◽  
Vol 17 ◽  
pp. 00256
Author(s):  
Murat Baimishev ◽  
Sergey Eremin ◽  
Kirill Plemyashov ◽  
Hamidulla Baimishev ◽  
Igor Konopeltsev ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Postpartum Period ◽  
Early Stage ◽  
Antioxidant Properties ◽  
Antioxidant Systems ◽  
Dry Period ◽  
Blood Samples ◽  
Start Up ◽  
Significant Difference ◽  
Duration Of Pregnancy

The purpose of the research is to determine the etiopathogenesis of reproductive dysfunction in highly productive cows. For this, one group of cows was formed on the principle of paranalogs in the amount of 37 animals inseminated in the first sexual hunt after calving, followed by taking blood samples from them using the Monovet system, considering the duration of pregnancy. During the start-up period, blood was taken 1–4 days before calving and on the first day after calving. A total of 253 blood samples were examined. Subsequently, depending on the effectiveness of insemination, animals were divided into two groups. The first group included inseminated cows after the first insemination (20 animals), the second group included 17 unfertilized cows after the first insemination. Subsequently, blood was taken from animals considering the course of childbirth and the postpartum period. Blood counts were studied according to generally accepted methods using certified equipment. The study found that at an early stage of pregnancy, cows have a significant difference in lipid metabolism and in their peroxidation, in the state of antioxidant systems compared to unstable animals. In the process of pregnancy development in cows, there is a decrease in the level of total lipids and their class, and the accumulation of products of transoxidation of lipids is reduced. In animals with retention of the placenta, a low lipid metabolism and a higher level of peroxidation were established already in the dry period. After calving, this difference increases. The obtained data can be used to develop an algorithm for the prevention of postpartum complications in cows by using substances with antioxidant properties.

Regulation of the tubulin polymerization-promoting protein by Ca2+/S100 proteins

Cell Calcium ◽  
2021 ◽  
Vol 96 ◽  
pp. 102404
Author(s):  
Seita Doi ◽  
Naoki Fujioka ◽  
Satomi Ohtsuka ◽  
Rina Kondo ◽  
Maho Yamamoto ◽  
...  
Keyword(s):  
S100 Proteins ◽  
Tubulin Polymerization ◽  
Tubulin Polymerization Promoting Protein

scholarly journals Exploring Diverse-Ring Analogues on Combretastatin A4 (CA-4) Olefin as Microtubule-Targeting Agents

2020 ◽  
Vol 21 (5) ◽  
pp. 1817 ◽  
Author(s):  
Ming-Yu Song ◽  
Qiu-Rui He ◽  
Yi-Lin Wang ◽  
Hao-Ran Wang ◽  
Tian-Cheng Jiang ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Annexin V ◽  
Docking Studies ◽  
Cytotoxic Agents ◽  
Tubulin Polymerization ◽  
Microtubule Network ◽  
Microtubule Targeting Agents ◽  
Ic50 Values ◽  
Tubulin Polymerization Inhibitor

Combretastatin-4 (CA-4) as a tubulin polymerization inhibitor draws extensive attentions. However, due to its weak stability of cis-olefin and poor metabolic stability, structure modifications on cis-configuration are being performed. In this work, we constructed a series of novel CA-4 analogues with linkers on olefin containing diphenylethanone, cis-locked dihydrofuran, α-substituted diphenylethanone, cyclobutane and cyclohexane on its cis-olefin. Cytotoxic activity of all analogues was measured by an SRB assay. Among them, compound 6b, a by-product in the preparation of diphenylethanone analogues, was found to be the most potent cytotoxic agents against HepG2 cells with IC50 values of less than 0.5 μM. The two isomers of 6b induced cellular apoptosis tested by Annexin V-FITC and propidium iodide (PI) double staining, arrested cells in the G2/M phase by PI staining analysis, and disrupted microtubule network by immunohistochemistry study in HepG2 cells. Moreover, 6b-(E) displayed a dose-dependent inhibition effect for tubulin assembly in in vitro tubulin polymerization assay. In addition, molecular docking studies showed that two isomers of 6b could bind efficiently at colchicine binding site of tubulin similar to CA-4.

scholarly journals Mitochondrial Dysfunction: The Road to Alpha-Synuclein Oligomerization in PD

2011 ◽  
Vol 2011 ◽  
pp. 1-20 ◽  
Author(s):  
A. R. Esteves ◽  
D. M. Arduíno ◽  
D. F. F. Silva ◽  
C. R. Oliveira ◽  
S. M. Cardoso
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Neuronal Cell ◽  
Alpha Synuclein ◽  
Vital Role ◽  
Microtubule Network ◽  
The Road ◽  
Species Production ◽  
Alpha Synuclein Aggregation

While the etiology of Parkinson's disease remains largely elusive, there is accumulating evidence suggesting that mitochondrial dysfunction occurs prior to the onset of symptoms in Parkinson's disease. Mitochondria are remarkably primed to play a vital role in neuronal cell survival since they are key regulators of energy metabolism (as ATP producers), of intracellular calcium homeostasis, of NAD+/NADH ratio, and of endogenous reactive oxygen species production and programmed cell death. In this paper, we focus on mitochondrial dysfunction-mediated alpha-synuclein aggregation. We highlight some of the findings that provide proof of evidence for a mitochondrial metabolism control in Parkinson's disease, namely, mitochondrial regulation of microtubule-dependent cellular traffic and autophagic lysosomal pathway. The knowledge that microtubule alterations may lead to autophagic deficiency and may compromise the cellular degradation mechanisms that culminate in the progressive accumulation of aberrant protein aggregates shields new insights to the way we address Parkinson's disease. In line with this knowledge, an innovative window for new therapeutic strategies aimed to restore microtubule network may be unlocked.

scholarly journals Phosphorylation Blocks the Activity of Tubulin Polymerization-promoting Protein (TPPP)

2007 ◽  
Vol 282 (40) ◽  
pp. 29531-29539 ◽  
Author(s):  
Emma Hlavanda ◽  
Eva Klement ◽  
Endre Kókai ◽  
János Kovács ◽  
Orsolya Vincze ◽  
...  
Keyword(s):  
Tubulin Polymerization ◽  
Tubulin Polymerization Promoting Protein
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