Journal of Inorganic Biochemistry最新文献

{"title":"Induction of ferroptosis of iridium(III) complexes localizing at the mitochondria and lysosome by photodynamic therapy","authors":"Yajie Niu ,&nbsp;Shuanghui Tang ,&nbsp;Jiongbang Li ,&nbsp;Chunxia Huang ,&nbsp;Yan Yang ,&nbsp;Lin Zhou ,&nbsp;Yunjun Liu ,&nbsp;Xiandong Zeng","doi":"10.1016/j.jinorgbio.2024.112808","DOIUrl":"10.1016/j.jinorgbio.2024.112808","url":null,"abstract":"<div><div>In this study, [Ir(ppy)₂(DMHBT)](PF₆) (ppy = deprotonated 1-phenylpyridine, DMHBT = 10,12-dimethylpteridino[6,7-f][1,10]phenanthroline-11,13-(10,12H)-dione, 8a), [Ir(bzq)₂(DMHBT)](PF₆) (bzq = deprotonated benzo[<em>h</em>]quinoline, 8b) and [Ir(piq)₂(DMHBT)](PF₆) (piq = deprotonated 1-phenylisoquinoline, 8c) were synthesized and characterized by HRMS, ¹³C NMR and ¹H NMR. In vitro cytotoxicity experiments showed that 8a, 8b, 8c show moderate cytotoxicity against B16 cells, while the cytotoxicity of the complexes 8a, 8b and 8c toward B16 cells was greatly improved upon light irradiation, which can be used as photosensitizers to exert anticancer efficacy in photodynamic therapy (PDT). After being taken up by cells, 8a, 8b, 8c were localized in the mitochondria, resulting in a large amount of Ca²⁺ in-flux, a burst release of ROS, a sustained opening of mitochondrial permeability transition pore, and a decrease of the mitochondrial membrane potential, which led to mitochondrial dysfunction and further activation of caspase 3 and Bcl-2 family proteins to induce apoptosis. Overloaded ROS reacted with polyunsaturated fatty acids on the cell membrane, and initiated lipid peroxidation, inhibited the x_c⁻-system-glutathione (GSH)-glutathione peroxidase 4 (GPX4) antioxidant defense system, and upregulated the expression of the damage-associated molecules, HMGB1, CRT, and HSP70. The presence of Fer-1 was effective on increasing the cell survival, which demonstrates that the complexes possess the potential to induce ferroptosis and immunogenic cell death. In addition, 8a, 8b and 8c induced autophagy by inhibiting the AKT/PI3K/mTOR signaling pathway, downregulating p62 and promoting Beclin-1 expression upon light irradiation.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"Article 112808"},"PeriodicalIF":3.8,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidant effect, DNA-binding, and transport of the flavonoid acacetin influenced by the presence of redox-active Cu(II) ion: Spectroscopic and in silico study","authors":"Marek Štekláč ,&nbsp;Michal Malček ,&nbsp;Peter Gajdoš ,&nbsp;Simona Vevericová ,&nbsp;Milan Čertík ,&nbsp;Marián Valko ,&nbsp;Vlasta Brezová ,&nbsp;Miriama Malček Šimunková","doi":"10.1016/j.jinorgbio.2024.112802","DOIUrl":"10.1016/j.jinorgbio.2024.112802","url":null,"abstract":"<div><div>Acacetin (AC) is a natural polyphenol from the group of flavonoids. It is well established that the behavior of flavonoids depends on the presence of redox-active substances; therefore, we aim to investigate their biological activity following the interaction with Cu(II) ion. Our study demonstrates that AC can effectively bind Cu(II) ions, as confirmed by UV–Vis and EPR spectroscopy as well as DFT calculations. AC appears as a potent scavenger against the model ABTS radical cation by itself, but this ability is significantly limited upon Cu(II) coordination. The possible mild synergistic effect of AC in the presence of vitamin C and glutathione was also shown by the ABTS^•+ test. In contrast, an inhibitory effect was observed in the presence of Cu(II) ions. The equimolar addition of AC to the model Fenton-like system containing Cu(II) did not have a noticeable effect on the concentration of hydroxyl radicals produced, but in its excess the formation of ^•OH decreased, as proved by EPR spin trapping. Absorption titrations and gel electrophoresis revealed effective binding to calf thymus (CT)-DNA with a stronger interaction for the Cu(II)-AC complex. The detailed mode of binding to biomolecules was described using molecular docking and molecular dynamics. Obtained results indicate that the double helix of DNA unwinds after interaction with the Cu(II)-AC complex. Fluorescence spectroscopy, employing human serum albumin (HSA), suggested a potential transport capacity for both AC and its Cu(II) complex.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"Article 112802"},"PeriodicalIF":3.8,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the mechanism: How does β-phosphoglucomutase from the haloacid dehalogenase superfamily catalyze the interconversion of β-d-glucose 1-phosphate and β-d-glucose 6-phosphate? A chemical perspective","authors":"Hao Zhang ,&nbsp;Mingming Zhang ,&nbsp;Kangning Zhu ,&nbsp;Yulan Feng ,&nbsp;Ling Yang ,&nbsp;Wanjian Ding","doi":"10.1016/j.jinorgbio.2024.112794","DOIUrl":"10.1016/j.jinorgbio.2024.112794","url":null,"abstract":"<div><div>The catalytic mechanisms of enzymes can be phylogenetically mapped corresponding to their catalytic structures. This mapping effectively elucidates the diversity of enzyme catalytic mechanisms and the emergence of new enzymatic activities within enzyme superfamilies. The haloacid dehalogenase (HAD) superfamily serves as an exemplary model system for comprehending the co-evolution of catalytic structures and mechanisms. This study delves into the mechanism underlying the functional divergence of <em>β</em>-phosphoglucomutase (<em>β</em>-PGM) from the phosphatase branch of the HAD superfamily, employing a chemical perspective. Through the construction and calculation of three models of varying scales using the Density Functional Theory method with B3LYP function, we aim to investigate the chemical mechanism driving this functional divergence of <em>β</em>-PGM from the HAD family. The computational results indicate that residues His20 and Lys76 in the second shell stabilize substrates and enhance the acid-base catalytic ability of Asp10. Additionally, residues Arg49, Ser116 and Asn118 facilitate substrate binding by engaging in close hydrogen bonding interactions with the substrates. Through cooperative action, these residues enable <em>β</em>-PGM to function as an efficient phosphoglucomutase. Through computational modeling and a chemical perspective, we unravel the mechanisms enabling <em>β</em>-PGM to convert <em>β</em>-<span>d</span>-glucose 1-phosphate to <em>β</em>-<span>d</span>-glucose 6-phosphate. Finally, based on the analysis of the evolutionary tree, we discussed and summarized the evolutionary relationships among different forms of metal cores of hydrolases.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"Article 112794"},"PeriodicalIF":3.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insight into uranyl binding by cyclic peptides from molecular dynamics and density functional theory","authors":"James A. Platts ,&nbsp;Iogann Tolbatov","doi":"10.1016/j.jinorgbio.2024.112793","DOIUrl":"10.1016/j.jinorgbio.2024.112793","url":null,"abstract":"<div><div>It is a challenging task to develop uranyl-chelating agents based on peptide chemistry. A recently developed cationic dummy atom model of uranyl in conjunction with the classical molecular dynamics simulation presents a helpful utility to study the chelation of uranyl by peptides with a low computational cost. In the present study, it was used to describe the chelation of uranyl by the cyclic decapeptide with 4 Glu residues cyc-GluArgGluProGlyGluTrpGluProGly and its derivatives containing two phosphorylated serines in place of two Glu, termed pS16, pS18, pS38, and pS68. The obtained structures were further studied by density functional theory (DFT) and subsequent density analysis. We show that a combination of steered molecular dynamics and simulated annealing, using standard forcefields for peptide with the cationic dummy atom model of uranyl, can quickly and reliably obtain binding modes of uranyl-peptide complexes. Classical molecular dynamics simulation in explicit water produces geometry very close to the DFT-optimized structure. The presence of uranyl completely changes the conformation of these cyclic peptides from unstructured to organised. The simulation of a peptide with two uranyl units explained why only the 1:1 ratio of peptide and chelated-uranyl is observed experimentally in most cases, by the insufficiency of the anionic residues for the chelation of two UO₂²⁺ units, but that pS16 can accommodate two such units.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"Article 112793"},"PeriodicalIF":3.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Schiff Base–platinum and ruthenium complexes and anti-Alzheimer properties","authors":"Salih Günnaz ,&nbsp;Esma Yildiz ,&nbsp;Ayça Tunçel Oral ,&nbsp;Fatma Yurt ,&nbsp;Arzum Erdem ,&nbsp;Sevil Irişli","doi":"10.1016/j.jinorgbio.2024.112790","DOIUrl":"10.1016/j.jinorgbio.2024.112790","url":null,"abstract":"<div><div>This study investigates the effects of Pt and Ru complexes containing a Schiff base with a diimine structure on Alzheimer's disease. The Schiff base (N1E,N2E)-N1,N2-bis(isoquinolin-4-ylmethylene)benzene-1,2-diamine (I) and the novel Pt(II) and Ru(II) complexes (Ia and Ib) were synthesized and characterized using FTIR, NMR (¹H, ¹³C), mass spectrometry, and elemental analyses. Their ability to inhibit amyloid beta (Aβ_1–42) aggregation was determined in vitro using the SH-SY5Y cell line. Fluorescence spectroscopy investigated the early aggregation kinetics and dose-dependent characteristics of Aβ₁_–₄₂ with the complexes. Transmission electron microscopy confirmed the results. Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI–TOF MS) and ¹H NMR spectroscopy examined the interaction with Aβ₁_–₁₆. Electrochemical analysis using square wave voltammetry monitored the interaction with Aβ₁_–₄₂. The synthesized complexes were active in inhibiting amyloid aggregation at a low molar ratio.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"Article 112790"},"PeriodicalIF":3.8,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metal (Au, Pt, Pd, Ni) Bis(dithiolene) complexes as dual-action agents combating cancer and trypanosomatid infections","authors":"Hadi Hachem ,&nbsp;Yann Le Gal ,&nbsp;Olivier Jeannin ,&nbsp;Dominique Lorcy ,&nbsp;Gonzalo Scalese ,&nbsp;Leticia Pérez-Díaz ,&nbsp;Dinorah Gambino ,&nbsp;António P. Matos ,&nbsp;Fernanda Marques","doi":"10.1016/j.jinorgbio.2024.112788","DOIUrl":"10.1016/j.jinorgbio.2024.112788","url":null,"abstract":"<div><div>Cancer and infection diseases pose severe threats to public health worldwide stressing the need for more effective and efficient treatments. Thus, the search for broad-spectrum activity drugs seems justifiable and urgent. Herein, we investigate the anticancer and antitrypanosomatid (anti-<em>Trypanosoma cruzi</em>) activities of eight monoanionic metal bis(dithiolene) complexes, [Ph₄P][M(R-thiazdt)₂] with Mⁿ⁺ = Au³⁺, Pt²⁺, Pd²⁺, Ni²⁺, containing <em>N</em>-alkyl-1,3-thiazoline-2-thione dithiolene ligands (R-thiazdt) with different alkyl groups (R = Et, <em>t</em>Bu). Compared to auranofin (AF) and cisplatin (CP), two reference drugs in clinical use, all complexes showed high anticancer activities against A2780 ovarian cancer cells (IC₅₀ values of 0.6–3.8 μM) some also being able to overcome CP resistance in A2780cisR cells. The selectivity index (SI), the IC₅₀ values on normal cells (HDF) <em>vs.</em> A2780 cells, indicated good anticancer specificity (SI &gt; 3) for most of the complexes but with clinical relevance for [Ph₄P][Pd(<em>t</em>Bu-thiazdt)₂] (SI = 10). All complexes showed relevant antitrypanosomatid activities (IC₅₀ values of 2.6–5.8 μM) some even exhibiting lower IC₅₀ values than the reference drug nifurtimox (NFX). The mechanism of cell death seemed to be mediated mainly by the formation of reactive oxygen species (ROS), although to lesser extent for the gold complexes but superior to AF. Although ROS play a role in the main apoptotic pathways, cell death by apoptosis was not evident as shown by the caspase-3/7 assay and the morphological cell features studies by electron microscopy (SEM). Results obtained evidenced that [Ph₄P][Pt(<em>t</em>Bu-thiazdt)₂] and [Ph₄P][Pd(<em>t</em>Bu-thiazdt)₂] complexes might have potential as novel anticancer and antitrypanosomatid agents as alternatives to current therapeutics.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"Article 112788"},"PeriodicalIF":3.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction of VVO2−hydrazonates with lysozyme","authors":"Maddalena Paolillo ,&nbsp;Giarita Ferraro ,&nbsp;Gurunath Sahu ,&nbsp;Pratikshya Das Pattanayak ,&nbsp;Eugenio Garribba ,&nbsp;Sourangshu Halder ,&nbsp;Riya Ghosh ,&nbsp;Bipul Mondal ,&nbsp;Pabitra B. Chatterjee ,&nbsp;Rupam Dinda ,&nbsp;Antonello Merlino","doi":"10.1016/j.jinorgbio.2024.112787","DOIUrl":"10.1016/j.jinorgbio.2024.112787","url":null,"abstract":"<div><div>Vanadium compounds (VCs) exhibit a broad range of pharmacological properties, with their most significant medical applications being in the treatment of cancer and diabetes. The therapeutic effects and mode of action of VCs may be associated with their ability to bind proteins and, consequently, understanding the VC–protein interaction is of paramount importance. Among the promising VCs, the V^VO₂ complex with the aroylhydrazone furan-2-carboxylic acid ((3-ethoxy-2-hydroxybenzylidene)hydrazide, hereafter denoted as VC1), deserves attention, since it exhibits cytotoxicity against various cancer cell lines, including HeLa. The interaction between VC1 and its analogue, denoted as VC2 (the dioxidovanadium(V) complex with (<em>E</em>)-<em>N</em>′-(1-(2-hydroxy-5-methoxyphenyl)ethylidene)furan-2-carbohydrazide), and hen egg white lysozyme (HEWL) was examined by UV–vis spectroscopy, fluorescence, circular dichroism, and X-ray crystallography. The interaction of VC1 and VC2 with HEWL does not alter the protein secondary and tertiary structure. Crystallographic studies indicate that the two metal complexes or V-containing fragments originating from VC1 and VC2 bind the protein via non-covalent interactions. Furthermore, when bound to HEWL, two VC1 molecules and two VC2 molecules form a supramolecular association stabilized by stacking interactions. This type of interaction could favour the binding of similar compounds to proteins and affect their biological activity.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"Article 112787"},"PeriodicalIF":3.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co(II), Cu(II), and Zn(II) thio-bis(benzimidazole) complexes induce apoptosis via mitochondrial pathway","authors":"Peter Antal ,&nbsp;Juraj Kuchár ,&nbsp;Luca Rigamonti ,&nbsp;Marie Kvasnicová ,&nbsp;Gabriel Gonzalez ,&nbsp;Lucie Rárová ,&nbsp;Miroslav Strnad ,&nbsp;Pavel Kopel","doi":"10.1016/j.jinorgbio.2024.112786","DOIUrl":"10.1016/j.jinorgbio.2024.112786","url":null,"abstract":"<div><div>The copper(II), cobalt(II), and zinc(II) complexes with 2-(1<em>H</em>-benzimidazol-2-ylmethylsulfanylmethyl)-1<em>H</em>-benzimidazole (<strong>tbb</strong>) and 2-[2-[2-(1<em>H</em>-benzimidazol-2-yl)ethylsulfanyl]ethyl]-1<em>H</em>-benzimidazole (<strong>tebb</strong>), [Cu(<em>tbb</em>)Cl₂] (<strong>1</strong>), [Co(<em>tbb</em>)Cl₂] (<strong>2</strong>), [Zn(<em>tbb</em>)Cl₂] (<strong>3</strong>), [Cu(tebb)Cl(H₂O)]Cl (<strong>4</strong>), [Co(tebb)Cl₂]_n·nCH₃OH (<strong>5</strong>) and [Zn(tebb)Cl(H₂O)]Cl (<strong>6</strong>), have been prepared and evaluated for antiproliferative activity. The structure of (<strong>4</strong>) was proved by X-ray diffraction crystallography.</div><div>The coordination compounds were tested for their cytotoxic activities in cancer cell lines in vitro. The lower IC₅₀ values were obtained for Co(II), Cu(II), and Zn(II) complexes with <strong>tebb</strong> in comparison with <strong>tbb</strong> complexes. Complex <strong>2</strong> showed strong antiproliferative selectivity for leukemia CEM cells and nontoxicity towards other tested cell lines and normal human cells (BJ and RPE-1). Proapoptotic activity of <strong>2</strong> and <strong>5</strong> were weaker than positive control cisplatin, but the big advantage of these complexes was their zero-cytotoxicity for normal healthy cells in contrast to the high cytotoxicity of cisplatin. The activation of apoptotic initiation phase was detected in neuroblastoma cancer cell line SH-SY5Y where <strong>5</strong> was cytotoxic without fragmentation of cells. Interestingly, complexes <strong>5</strong>, <strong>6</strong>, and tebb, together with cisplatin, dramatically impaired the mitochondrial membrane potential of SH-SY5Y after 72 h. Taken together, we demonstrated that our compounds trigger apoptosis via the mitochondrial pathway.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"Article 112786"},"PeriodicalIF":3.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitroxidative stress in human neural progenitor cells: In situ measurement of nitric oxide/peroxynitrite imbalance using metalloporphyrin nanosensors","authors":"Nouf Alsiraey ,&nbsp;Howard D. Dewald","doi":"10.1016/j.jinorgbio.2024.112785","DOIUrl":"10.1016/j.jinorgbio.2024.112785","url":null,"abstract":"<div><div>Nitric oxide (NO) is an essential inorganic signaling molecule produced by constitutive NO synthase (cNOS) in the neurological system. Under pathological conditions, NO rapidly reacts with superoxide (O₂^•−) to generate peroxynitrite (ONOO^¯). Elevated ONOO^¯ concentrations induce nitroxidative stress, potentially contributing to numerous pathological processes as observed in neurodegenerative diseases including Alzheimer's disease (AD). Metalloporphyrin nanosensors, (200<span><math><mo>–</mo></math></span>300 nm diameter), were applied to quantify the NO/ONOO^¯ balance produced by a single human neural progenitor cell (hNPC), <em>in situ</em>. These nanosensors, positioned in proximity of 4<span><math><mo>–</mo></math></span>5 ± 1 μm from the hNPCs membrane, enabled real-time measurement of NO and ONOO^¯ concentrations following calcium ionophore (CaI) stimulation. The ratio of NO to ONOO^¯ concentration ([NO]/[ONOO^¯]) was established for the purpose of quantifying nitroxidative stress levels. Normal hNPCs produced a maximum of 107 ± 1 nmol/L of NO and 451 ± 7 nmol/L of ONOO^¯, yielding a [NO]/[ONOO^¯] ratio of 0.25 ± 0.005. In contrast, the model of the dysfunctional hNPCs, for long-term (48 h) amyloid-beta 42 (Aβ₄₂) exposure significantly altered NO/ONOO^¯ production. The NO level decreased to 14 ± 0.1 nmol/L, while ONOO^¯ increased to 843 ± 0.8 nmol/L, resulting in a 94 % reduction of the [NO]/[ONOO^¯] ratio to 0.016 ± 0.0001. The [NO]/[ONOO^¯] ratio is determined by this work as a possible biomarker of nNOS efficiency and hNPC dysfunction, with implications for neurodegenerative disorders such as AD. Promising applications in the early medical diagnosis of neurological illnesses, electrochemical metalloporphyrin nanosensors demonstrate efficacy in real-time nitroxidative stress monitoring.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"263 ","pages":"Article 112785"},"PeriodicalIF":3.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper(II) complex with 1-allylimidazole induces G2/M cell cycle arrest and suppresses A549 cancer cell growth by attenuating Wnt, JAK-STAT, and TGF-β signaling pathways","authors":"Katarzyna Gałczyńska ,&nbsp;Aneta Węgierek-Ciuk ,&nbsp;Katarzyna Durlik-Popińska ,&nbsp;Paulina Żarnowiec ,&nbsp;Krystyna Kurdziel ,&nbsp;Michał Arabski","doi":"10.1016/j.jinorgbio.2024.112791","DOIUrl":"10.1016/j.jinorgbio.2024.112791","url":null,"abstract":"<div><div>The main aim of the study was to investigate the molecular mechanism of action of the potentially anti-cancer agent copper(II) complex with 1-allylimidazole [Cu(1-allim)₄(NO₃)₂] using the A549 lung cancer line, toward which it is selectively cytotoxic. Gene expression analysis showed that the complex caused apoptosis through WNT, JAK-STAT, and TGF-β pathways. The complex induced DNA damage, ROS production, and depolarization of the mitochondrial membrane, suggesting that its toxicity is likely due to induction of the intrinsic apoptosis pathway. It also arrested the cell cycle at G2/M phase. Particularly noteworthy is that it inhibited the WNT pathway, a target for lung cancer therapies. Its complex mechanism of action may hinder the acquisition of immunity by cancer cells.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"Article 112791"},"PeriodicalIF":3.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}