Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology最新文献

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Spatial Organization of the Components of the Serotonergic System in the Early Mouse Development 小鼠早期发育过程中血清素能系统成分的空间组织
IF 1.1
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2024-01-17 DOI: 10.1134/S1990747823060041
V. S. Frolova, A. D. Ivanova, M. S. Konorova, Yu. B. Shmukler, D. A. Nikishin
{"title":"Spatial Organization of the Components of the Serotonergic System in the Early Mouse Development","authors":"V. S. Frolova,&nbsp;A. D. Ivanova,&nbsp;M. S. Konorova,&nbsp;Yu. B. Shmukler,&nbsp;D. A. Nikishin","doi":"10.1134/S1990747823060041","DOIUrl":"10.1134/S1990747823060041","url":null,"abstract":"<p>Serotonin is a regulator of early embryonic development and has a complete functional system in preimplantation mammalian embryos. In the present work, the spatial distribution of serotonin, the vesicular monoamine transporter VMAT2, and the 5-HT<sub>1D</sub> and 5-HT<sub>2A</sub> receptors at different stages of early embryonic development was described. Serotonin, the VMAT2 transporter, and the 5-HT<sub>1D</sub> receptor are visualized in the cortical compartment of cells, whereas the 5-HT<sub>2A</sub> receptor has a more even distribution throughout the cytoplasm. The comparison showed that there were no statistically significant differences between the immunoreactive particle sizes of serotonin and the VMAT2 transporter, suggesting the presence of vesicles in which serotonin accumulates with the involvement of VMAT2 for further intercellular signal transduction. Moreover, the patterns of immunoreactivity of the two serotonin receptors, 5-HT<sub>1D</sub> and 5-HT<sub>2A</sub>, differ markedly, which may indicate that they simultaneously serve different functions in early embryogenesis.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"17 1 supplement","pages":"S59 - S64"},"PeriodicalIF":1.1,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139499223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
α1-Adrenergic Receptors Control the Activity of Sinoatrial Node by Modulating Transmembrane Transport of Chloride Anions α1-肾上腺素能受体通过调节氯离子的跨膜转运控制心房结的活动
IF 1.1
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2024-01-17 DOI: 10.1134/S1990747823070061
Y. A. Voronina, A. V. Fedorov, M. A. Chelombitko, U. E. Piunova, V. S. Kuzmin
{"title":"α1-Adrenergic Receptors Control the Activity of Sinoatrial Node by Modulating Transmembrane Transport of Chloride Anions","authors":"Y. A. Voronina,&nbsp;A. V. Fedorov,&nbsp;M. A. Chelombitko,&nbsp;U. E. Piunova,&nbsp;V. S. Kuzmin","doi":"10.1134/S1990747823070061","DOIUrl":"10.1134/S1990747823070061","url":null,"abstract":"<p>Norepinephrine (NE), which is released by sympathetic nerve endings, causes an increase in the frequency of spontaneous action potentials in the pacemaker cardiomyocytes of the sinoatrial node (SAN) of the heart. This results in an increase in heart rate (HR). Two types of postsynaptic adrenoreceptors (ARs), α1-AR and β-AR, mediate the effects of NE. The role of α1-AR in the sympathetic control of heart rate and SAN automaticity, as well as the membrane mechanisms involved in α1-AR-mediated pacemaker control, have not yet been elucidated. In this study, we utilized immunofluorescence confocal microscopy to examine the distribution of α1A-AR in the SAN of rats. Additionally, we assessed the expression of α1A-AR mRNA in the SAN tissue using RT-PCR. Furthermore, we investigated the impact of α1-AR stimulation on key functional parameters of the pacemaker, including the corrected sinus node recovery time (SNRT/cSNRT) and the SAN accommodation, using the Langendorff perfused heart technique. We also used optical mapping of the electrical activity of perfused, isolated tissue preparations to study the effect of α1-AR stimulation on the spatiotemporal characteristics of SAN excitation. We tested the effects of chloride transmembrane conductance blockade on alteration of functional parameters and pattern of SAN excitation caused by α1-AR. Fluorescent signals corresponding to α1A-AR have been identified in SAN cardiomyocytes, indicating the presence of α1A-AR at protein level. The expression of α1A-AR in SAN has been also confirmed at the mRNA level. The stimulation of α1-AR affects SAN functioning. Phenylephrine (PHE) utilized as α1A-AR agonist caused a decrease in SNRT/cSNRT, as well as an acceleration of SAN accommodation. These effects were rate dependent and were observed in a high frequency range of pacemaker tissue stimulation. PHE induces changes in the excitation pattern of the SAN. The effects of PHE on functional parameters and SAN excitation pattern are attenuated by Ca<sup>2+</sup>-dependent chloride channel blocker NPPB but remains unaffected by the protein kinase C inhibitor BIM. Our results suggest that cardiac α1-ARs are important for maintaining function of SAN pacemaker at high heart rates and that α1-AR signalling cascades in the SAN by targeting Ca<sup>2+</sup>-dependent chloride channels are involved in the α1-adrenergic modulation of the electrophysiological properties of the heart pacemaker.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"17 1 supplement","pages":"S39 - S50"},"PeriodicalIF":1.1,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139499178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ATP Causes Contraction of Denervated Skeletal Muscles ATP 能使失去神经支配的骨骼肌收缩
IF 1.1
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2024-01-17 DOI: 10.1134/S1990747823060065
A. E. Khairullin, A. Y. Teplov, S. N. Grishin, A. U. Ziganshin
{"title":"ATP Causes Contraction of Denervated Skeletal Muscles","authors":"A. E. Khairullin,&nbsp;A. Y. Teplov,&nbsp;S. N. Grishin,&nbsp;A. U. Ziganshin","doi":"10.1134/S1990747823060065","DOIUrl":"10.1134/S1990747823060065","url":null,"abstract":"<p>The ability of humoral agonists (and their persistent analogues) to induce contractions of denervated <i>m. soleus</i> and <i>m. extensor</i> <i>digitorum longus</i> of mice was investigated. Earlier, we found a change in the effectiveness of the ATP modulating effect under some non-physiological factors in the neuromuscular synapses of rodents. The aim of this study was to evaluate the effect of ATP on the contractility of isolated skeletal muscles of a mouse after traumatic denervation. It has been shown that 28-day denervation led to an increase in the strength of contractions of <i>m. soleus</i> and <i>m. extensor digitorum longus</i> caused by an acetylcholine analog. ATP application induced a contraction of denervated muscles, but not of intact ones. In the presence of a non-selective P2 receptor antagonist suramin, the effect of ATP ceased. We suggest that activation of postsynaptic P2X receptors of denervated muscles could cause their contraction. Apparently, this effect was caused by an increase in the expression of postsynaptic receptors in response to a violation of neurotrophic control and the conductive ability of the nerve fiber.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"17 1 supplement","pages":"S73 - S77"},"PeriodicalIF":1.1,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139499218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Modulation of Adhesion and Migration of NIH/3T3 Cells in Collagen Materials by Taxifolin Derivatives 紫杉叶素衍生物对胶原蛋白材料中 NIH/3T3 细胞粘附和迁移的调节作用
IF 1.1
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2024-01-17 DOI: 10.1134/S1990747823070048
Yu. V. Shatalin, M. I. Kobyakova, V. S. Shubina
{"title":"Modulation of Adhesion and Migration of NIH/3T3 Cells in Collagen Materials by Taxifolin Derivatives","authors":"Yu. V. Shatalin,&nbsp;M. I. Kobyakova,&nbsp;V. S. Shubina","doi":"10.1134/S1990747823070048","DOIUrl":"10.1134/S1990747823070048","url":null,"abstract":"<p>One of the urgent tasks of tissue engineering is the development of stable non-toxic materials that support cell migration during tissue regeneration. This study was aimed at obtaining new gel materials based on collagen and derivatives of taxifolin, taxifolin pentaglutarate and a conjugate of taxifolin with glyoxylic acid and investigating their properties. It was shown that an increase in the proportion of polyphenols in the gel led to a decrease in the rate of degradation of the material. The obtained materials did not negatively affect the viability of NIH/3T3 mouse fibroblasts. The cells were attached to the surface of the materials and spread out on the surface of the material containing taxifolin pentaglutarate. It was also found that fibroblasts migrated through the obtained materials. An increase in the proportion of the conjugate of taxifolin with glyoxylic acid in the material led to inhibition of migration through the material, whereas an increase in the proportion of taxifolin pentaglutarate in the material, on the contrary, led to a significant increase in cell migration through the material. The results obtained indicated the possibility of modulating cell adhesion and migration in biomaterials by including various taxifolin derivatives in their composition. Thus, materials obtained on the basis of collagen and taxifolin derivatives may be of interest for regenerative medicine.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"17 1 supplement","pages":"S85 - S93"},"PeriodicalIF":1.1,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140888253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Activation of Complement Factor C3/C3b Deposition on the of Endothelial Cell Surface by Histamine As one of the Causes of Endothelium Damage in COVID-19 组胺激活内皮细胞表面的补体因子 C3/C3b 沉积是 COVID-19 内皮损伤的原因之一
IF 1.1
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2024-01-17 DOI: 10.1134/S1990747823070012
P. P. Avdonin, Yu. V. Markitantova, E. Yu. Rybakova, N. V. Goncharov, P. V. Avdonin
{"title":"Activation of Complement Factor C3/C3b Deposition on the of Endothelial Cell Surface by Histamine As one of the Causes of Endothelium Damage in COVID-19","authors":"P. P. Avdonin,&nbsp;Yu. V. Markitantova,&nbsp;E. Yu. Rybakova,&nbsp;N. V. Goncharov,&nbsp;P. V. Avdonin","doi":"10.1134/S1990747823070012","DOIUrl":"10.1134/S1990747823070012","url":null,"abstract":"<p>Endothelial damage as a result of complement system activation is one of the causes of thrombotic complications in COVID-19. Factor C3 plays a key role in this process. The attachment of its proteolysis product C3b to the membrane initiates the beginning of the formation of membrane attack complex C5b-9, which forms a pore in the plasma membrane and cell death. In the present study, we investigated how histamine, secreted in the body at sites of inflammation by leukocytes and mast cells, might affect the binding of C3b to endothelial cells (ECs). FITS-conjugated antibodies against the C3c fragment were used to visualize it. These antibodies bind to intact C3 and to C3b but not to C3a. We have shown that incubation of human blood plasma with cultured ECs from human umbilical vein results in accumulation of C3/C3b as rounded local and diffuse foci on the surface of the cell monolayer. Pre-activation of ECs by histamine increases the number of C3/C3b attachment sites. These data suggest that histamine can enhance endothelial layer damage during hyperactivation of the complement system in COVID-19 and endotheliopathies caused by other diseases.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"17 1 supplement","pages":"S51 - S58"},"PeriodicalIF":1.1,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139499066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular Model of Norfloxacin Translocation through Yersinia pseudotuberculosis Porin OmpF Channel: Electrophysiological and Molecular Modeling Study 诺氟沙星通过耶尔森氏菌茯苓 OmpF 通道转运的分子模型:电生理学和分子建模研究
IF 1.1
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2024-01-17 DOI: 10.1134/S1990747823070024
D. K. Chistyulin, E. A. Zelepuga, V. L. Novikov, N. N. Balaneva, V. P. Glazunov, E. A. Chingizova, V. A. Khomenko, O. D. Novikova
{"title":"Molecular Model of Norfloxacin Translocation through Yersinia pseudotuberculosis Porin OmpF Channel: Electrophysiological and Molecular Modeling Study","authors":"D. K. Chistyulin,&nbsp;E. A. Zelepuga,&nbsp;V. L. Novikov,&nbsp;N. N. Balaneva,&nbsp;V. P. Glazunov,&nbsp;E. A. Chingizova,&nbsp;V. A. Khomenko,&nbsp;O. D. Novikova","doi":"10.1134/S1990747823070024","DOIUrl":"10.1134/S1990747823070024","url":null,"abstract":"<p>The interaction of the <i>Yersinia pseudotuberculosis</i> porin OmpF (YpOmpF) with the fluoroquinolone antibiotic norfloxacin (Nf) and its derivatives (mono- and dihydrochloride) was studied using the bilayer lipid membrane (BLM) method, molecular modeling, and antibacterial activity testing. An asymmetric behavior of the Nf charged molecules was found: NfH<sup>+1</sup> and Nf2H<sup>+2</sup> moved through the YpOmpF channel, depending on the membrane voltage and on the side where the antibiotic was added. The electrophysiological data were confirmed by computational modeling. For charged forms of the antibiotic, the presence of two peripheral high-affinity binding sites (NBS1 and NBS2), as well as an asymmetric current blocking site (NBS3) near the channel constriction zone were detected. The NBS1 site located near the channel mouth has almost the same affinity for both charged forms of Nf, while the localization of the more energetically favorable NBS2 site for the two salt forms of the antibiotic differs significantly. Nf has only one binding site near the constriction zone, which is a cluster of sites with a lower overall affinity compared to the peripheral binding sites mentioned above. Slight differences were found in the antibacterial activity of the three forms of Nf, which is likely due to their different charge states and, accordingly, different permeability and/or ability to bind within the YpOmpF channel.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"17 1 supplement","pages":"S20 - S38"},"PeriodicalIF":1.1,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139499260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sensors of Intracellular Nucleic Acids Activating STING-Dependent Production of Interferons in Immunocompetent Cells 细胞内核酸传感器激活 STING 依赖性免疫细胞产生干扰素
IF 1.1
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2024-01-17 DOI: 10.1134/S199074782307005X
L. V. Smolyaninova, O. N. Solopova
{"title":"Sensors of Intracellular Nucleic Acids Activating STING-Dependent Production of Interferons in Immunocompetent Cells","authors":"L. V. Smolyaninova,&nbsp;O. N. Solopova","doi":"10.1134/S199074782307005X","DOIUrl":"10.1134/S199074782307005X","url":null,"abstract":"<p>Currently, foreign DNA or RNA sensor proteins, which play an important role in innate immunity, are of great interest as a new avenue for cancer immunotherapy. This review considers the functioning of cytoplasmic nucleic acid sensors such as cGAS, STING, IFI16, AIM2, DAI, DDX41, DNA-PK, MRE-11, and TREX1, involved in activating the production of various cytokines.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"17 1 supplement","pages":"S1 - S19"},"PeriodicalIF":1.1,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139499313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Role of the HL-7 Peptide in the Induction of the Intrinsic Signalling Pathway of Apoptosis in HeLa Cancer Cells HL-7 肽在诱导 HeLa 癌细胞凋亡的内在信号途径中的作用
IF 1.1
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2024-01-17 DOI: 10.1134/S1990747823070036
Zahra Setayesh-Mehr, Mohammad Hajitabar, Asghar Parsaei
{"title":"The Role of the HL-7 Peptide in the Induction of the Intrinsic Signalling Pathway of Apoptosis in HeLa Cancer Cells","authors":"Zahra Setayesh-Mehr,&nbsp;Mohammad Hajitabar,&nbsp;Asghar Parsaei","doi":"10.1134/S1990747823070036","DOIUrl":"10.1134/S1990747823070036","url":null,"abstract":"<p>Anticancer peptides are of interest for cancer treatment. Nowadays, the process of apoptosis is considered a molecular target for cancer therapy. In the present study, the toxic effect of the HL-7 peptide on cervical cancer cells HeLa was investigated using the MTT assay. Also, the expression levels of <i>Bax</i>, <i>Bcl-2</i>, <i>p53</i>, <i>caspase-3</i>, <i>PTEN</i>, and <i>Akt</i> genes in HeLa cells treated with HL-7 were assessed by real-time PCR. Besides, the percentage of cells in early and late stages of apoptosis was determined using flow cytometry. The obtained results indicated that the peptide HL-7 inhibited growth of HeLa cells with IC<sub>50</sub> of 31 μM. The expression levels of <i>Bax</i>, <i>p53</i>, <i>caspase-3</i>, and <i>PTEN</i> genes were increased in HeLa cells treated with the HL-7 peptide as compared to untreated HeLa cells, while the expression levels of <i>Bcl-2</i> and <i>Akt</i> genes was decreased (<i>p</i> &lt; 0.05). The results of flow cytometry analysis indicated a high percentage of cells in the late apoptosis stage (<i>p</i> &lt; 0.05). Our findings suggest that peptide HL-7 can be involved in inducing the mitochondria-dependent apoptosis pathway. However, additional studies are needed to elucidate the exact mechanism of action of the peptide on HeLa cancer cells and the prospects for its therapeutic use in the clinic.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"17 1 supplement","pages":"S78 - S84"},"PeriodicalIF":1.1,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139499156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Involvement of the Mitochondrial Ca2+-Independent Phospholipase iPLA2 in the Induction of Mitochondrial Permeability Transition Pore by Long-Chain Acylcarnitines 线粒体 Ca2+ 依赖性磷脂酶 iPLA2 参与了长链酰基肉碱对线粒体通透性转换孔的诱导作用
IF 1.1
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2023-12-10 DOI: 10.1134/S1990747823050045
N. I. Fedotcheva, E. V. Grishina, V. V. Dynnik
{"title":"Involvement of the Mitochondrial Ca2+-Independent Phospholipase iPLA2 in the Induction of Mitochondrial Permeability Transition Pore by Long-Chain Acylcarnitines","authors":"N. I. Fedotcheva,&nbsp;E. V. Grishina,&nbsp;V. V. Dynnik","doi":"10.1134/S1990747823050045","DOIUrl":"10.1134/S1990747823050045","url":null,"abstract":"<p>It is known that activated derivatives of long-chain fatty acids acylcarnitines (LCAC) are considered the most toxic, which, along with calcium, can participate in the induction of the mitochondrial pore, involving various types of phospholipases. In this study, the effect of inhibitors of Ca<sup>2+</sup>-independent and Ca<sup>2+</sup>-dependent phospholipases, as well as an inhibitor of carnitine palmitoyltransferase on the induction of pores with <i>D</i>,<i>L</i>-palmitoylcarnitine (PC, C16:0) was investigated. In experiments on isolated rat liver mitochondria, the effect of PC on mitochondrial respiration rate, membrane potential (ΔΨm) and mitochondrial swelling during oxidation of glutamate and pyruvate or succinate was studied. It was shown that inhibitors of carnitine palmitoyltransferase-1 etomoxir 2, Ca<sup>2+</sup>-dependent phospholipase cPLA2 aristolochic acid or Ca<sup>2+</sup>-independent phospholipase iPLA2γ bromoenol lactone and PACOCF3 caused an increase in critical concentrations of <i>D</i>,<i>L</i>-palmitoylcarnitine (PC*), which were required to decrease the membrane potential and induce mitochondrial swelling. In the ADP activated state 3 (ADP + Mg<sup>2+</sup> + hexokinase), Ethomoxir 2 and aristolochic acid promoted the inhibition of respiration and dissipation of membrane potential caused by excess of PC, while phospholipase inhibitors iPLA2γ PACOCF3 and bromoenol lactone provided a pronounced protective effect. Inhibition of iPLA2γ prevented the decrease of ΔΨm and inhibition of respiration caused by PC. Thus, the results obtained indicated the involvement of mitochondrial phospholipase iPLA2γ in the induction of the mitochondrial pore by long-chain acylcarnitines.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"17 4","pages":"325 - 331"},"PeriodicalIF":1.1,"publicationDate":"2023-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138566439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ethylmethylhydroxypyridine Succinate Limits Stress-Induced Neuroinflammation in the Cerebral Cortex of Old Rats 甲基羟基吡啶琥珀酸乙酯可限制应激诱发的老年大鼠大脑皮层神经炎症
IF 1.1
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2023-12-10 DOI: 10.1134/S1990747823050124
O. L. Terekhina, Y. I. Kirova
{"title":"Ethylmethylhydroxypyridine Succinate Limits Stress-Induced Neuroinflammation in the Cerebral Cortex of Old Rats","authors":"O. L. Terekhina,&nbsp;Y. I. Kirova","doi":"10.1134/S1990747823050124","DOIUrl":"10.1134/S1990747823050124","url":null,"abstract":"<p>In the aging and the development of age-associated diseases, the trigger mechanism is the hyperactivation of the hypothalamic-pituitary-adrenal neuroendocrine axis, hypersecretion of glucocorticoids, which, under excessive and long-term stimulation, have inflammatory and degenerative effects. Chronic stress exacerbates glucocorticoid-dependent atrophic changes in the aging brain, increases neuroinflammation and neurological dysfunction, and is a key risk factor for Alzheimer’s disease. In the correction of aseptic neuroinflammation in elderly and senile patients, the use of anti-inflammatory agents that exhibit anti-glucocorticoid (pro-anabolic) and anti-glutamate (anti-excitotoxic) effects is pathogenetically justified. Succinate/SUCNR1 signalling is involved in the development of immunomodulatory, trophic, and anti-hypoxic effects; however, its role in the mechanisms of stress response remains unexplored. The aim of this study was to assay the impact of succinate/SUCNR1 signalling on the development of stress-induced neuroinflammation in the cerebral cortex of old rats. The work was performed on outbred albino male rats aged 18 months. Chronic restraint stress was modelled by immobilizing animals in individual plastic cases for 6 h daily for 5 days. Mexidol (2-ethyl-6-methyl-3-hydroxypyridine (EMHP) succinate) was used as a form of succinate that crosses the blood-brain barrier. Mexidol was administered intraperitoneally to old rats at a dose of 100 mg/kg daily for 5 days 15 min before the onset of stress. The levels of proinflammatory cytokines (IL-1β, TNF-α), anti-inflammatory cytokines (TGF-β1, IL-10), glucocorticoid receptors (GRα), transcriptional coactivator PGC-1α, succinate receptor SUCNR1/GPR91, and vascular endothelial growth factor (VEGF) were determined by immunoblotting in cerebral cortex (CC) samples. It was shown that chronic immobilization stress caused an increase in the level of IL-1β and TNF-α during stress, which was accompanied by a decrease in the content of anti-inflammatory cytokines, SUCNR1, GRα, PGC-1α. The course administration of EMHP succinate limited the development of stress-induced neuroinflammation in the CC of old rats and prevented a decrease in the levels of SUCNR1, IL-10, TGF-β1, PGC-1α, and GRα. The study reveals for the first time the stress-protective potential of succinate/SUCNR1 signalling in the brain of old rats associated with the activation of PGC-1α-dependent anti-inflammatory mechanisms under conditions of chronic stress.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"17 4","pages":"311 - 318"},"PeriodicalIF":1.1,"publicationDate":"2023-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138565807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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