Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gallic acid-mitochondria targeting sequence-H₃R₉ induces mitochondria-targeted cytoprotection.

ABSTRACT: The development of selective targeting of drug molecules towards the mitochondria is an important issue related to therapy efficacy. In this study, we report that gallic acid (GA)-mitochondria targeting sequence (MTS)-H₃R₉ exhibits a dual role as a mitochondria-targeting vehicle with antioxidant activity for disease therapy. In viability assays, GA-MTS-H₃R₉ showed a better rescue action compared to that of MTS-H₃R₉. GA-MTS-H₃R₉ dramatically exhibited cell penetration and intercellular uptake compared to MTS and fit escape from lysosome release to the cytosol. We demonstrated the useful targeting of GA-MTS-H₃R₉ towards mitochondria in AC16 cells. Also, we observed that the antioxidant properties of mitochondrial-accrued GA-MTSH₃R₉ alleviated cell damage by reactive oxygen species production and disrupted mitochondrial membrane potential. GA-MTS-H₃R₉ showed a very increased cytoprotective effect against anticancer activity compared to that of MTS-H₃R₉. We showed that GA-MTS-H₃R₉ can act as a vehicle for mitochondria-targeting and as a reagent for therapeutic applications intended for cardiovascular disease treatment.

SUBMITTER: Bae Y

PROVIDER: S-EPMC8723982 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Gallic Acid.

Project description:Anhydrous 3,4,5-trihy-droxy-benzoic acid, C(7)H(6)O(5), is essentially planar, with its non-H atoms exhibiting mean and maximum deviations from coplanarity of 0.014 and 0.0377?(5)?Å, respectively. The C-C-C-OH torsion angle about the bond linking the carboxyl group to the benzene ring is -0.33?(10)°. In the crystal, the -COOH groups form centrosymmetric hydrogen-bonded cyclic dimers [graph set R(2) (2)(8)] and the phenolic -OH groups participate in both intra- and inter-molecular hydrogen bonds, forming a three-dimensional network structure.

| S-EPMC3051435 | biostudies-literature

Gallic acid induces necroptosis via TNF-? signaling pathway in activated hepatic stellate cells.

Project description:Gallic acid (3, 4, 5-trihydroxybenzoic acid, GA), a natural phenolic acid widely found in gallnuts, tea leaves and various fruits, possesses several bioactivities against inflammation, oxidation, and carcinogenicity. The beneficial effect of GA on the reduction of animal hepatofibrosis has been indicated due to its antioxidative property. However, the cytotoxicity of GA autoxidation causing cell death has also been reported. Herein, we postulated that GA might target activated hepatic stellate cells (aHSCs), the cell type responsible for hepatofibrosis, to mitigate the process of fibrosis. The molecular cytotoxic mechanisms that GA exerted on aHSCs were then analyzed. The results indicated that GA elicited aHSC programmed cell death through TNF-?-mediated necroptosis. GA induced significant oxidative stress through the suppression of catalase activity and the depletion of glutathione (GSH). Elevated oxidative stress triggered the production of TNF-? facilitating the undergoing of necroptosis through the up-regulation of key necroptotic regulatory proteins TRADD and receptor-interacting protein 3 (RIP3), and the inactivation of caspase-8. Calmodulin and calpain-1 activation were engaged, which promoted subsequent lysosomal membrane permeabilization (LMP). The TNF-? antagonist (SPD-304) and the RIP1 inhibitor (necrostatin-1, Nec-1) confirmed GA-induced TNFR1-mediated necroptosis. The inhibition of RIP1 by Nec-1 diverted the cell death from necroptosis to apoptosis, as the activation of caspase 3 and the increase of cytochrome c. Collectively, this is the first report indicating that GA induces TNF signaling-triggered necroptosis in aHSCs, which may offer an alternative strategy for the amelioration of liver fibrosis.

| S-EPMC4376672 | biostudies-literature

Hydrothermal synthesis of Bi<sub>2</sub>Se<sub>3</sub> nanosheets by using gallic acid as a reductant.

Project description:In this work, a simple and reproducible hydrothermal synthesis was employed to synthesize two-dimensional Bi2Se3 nanosheets by using gallic acid as a reductant. Meanwhile, the effects of the amounts of gallic acid and sodium hydroxide and the surfactant Triton X-100 on phase composition and morphology of the obtained Bi2Se3 were also studied. The results reveal that gallic acid could effectively reduce Se4+ to Se2- and gave rise to the formation of Bi2Se3. Additionally, keeping the reaction conditions of molar ratio of gallic acid to the precursor elements (Bi + Se) at 1 to 1 (or higher) and using strong alkaline solutions were the key factors to synthesize high purity crystalline Bi2Se3 nanosheets. Furthermore, flower-like Bi2Se3 composed of nanosheets with a dozen nanometer thickness could be easily fabricated by adding appropriate amounts of Triton X-100. This work provides a novel approach for synthesis of ultra-thin Bi2Se3 nanosheets in a controllable manner.

| S-EPMC9116176 | biostudies-literature

Gallic acid pyridine monosolvate.

Project description:IN THE TITLE COMPOUND (SYSTENATIC NAME: 3,4,5-trihy-droxy-benzoic acid pyridine monosolvate), C(5)H(5)N·C(7)H(6)O(5), the gallic acid mol-ecule is essentially planar (r.m.s deviation = 0.0766 Å for non-H atoms) and is linked to the pyridine mol-ecule by an O-H⋯N hydrogen bond. An intra-molecular O-H⋯O hydrogen bond occurs in the gallic acid mol-ecule. The gallic acid and pyridine mean planes make a dihedral angle 12.6 (3)°. Inter-molecular O-H⋯O and O-H⋯N hydrogen bonding involving the hy-droxy and carboxyl groups and the pyridine mol-ecule, and π-π inter-actions between inversion-related pyridines [centroid-centroid distance = 3.459 (6) Å] and between pyridine and benzene rings [centroid-centroid distance = 3.548 (6) Å], lead to a three-dimensional network in the crystal.

| S-EPMC3247482 | biostudies-literature

De Novo Development of Mitochondria-Targeted Molecular Probes Targeting Pink1.

Project description:Mitochondria play central roles in maintaining cellular metabolic homeostasis, cell survival and cell death, and generate most of the cell's energy. Mitochondria maintain their homeostasis by dynamic (fission and fusion) and quality control mechanisms, including mitophagy, the removal of damaged mitochondria that is mediated mainly by the Pink1/Parkin pathway. Pink1 is a serine/threonine kinase which regulates mitochondrial function, hitherto many molecular mechanisms underlying Pink1 activity in mitochondrial homeostasis and cell fate remain unknown. Peptides are vital biological mediators that demonstrate remarkable potency, selectivity, and low toxicity, yet they have two major limitations, low oral bioavailability and poor stability. Herein, we rationally designed a linear peptide that targets Pink1 and, using straightforward chemistry, we developed molecular probes with drug-like properties to further characterize Pink1. Initially, we conjugated a cell-penetrating peptide and a cross-linker to map Pink1's 3D structure and its interaction sites. Next, we conjugated a fluorescent dye for cell-imaging. Finally, we developed cyclic peptides with improved stability and binding affinity. Overall, we present a facile approach to converting a non-permeable linear peptide into a research tool possessing important properties for therapeutics. This is a general approach using straightforward chemistry that can be tailored for various applications by numerous laboratories.

| S-EPMC9181014 | biostudies-literature

Mitochondria-targeted hydroxyurea inhibits OXPHOS and induces antiproliferative and immunomodulatory effects.

Project description:Hydroxyurea (HU), an FDA-approved drug for treating sickle cell disease, is used as an antitumor drug alone and together with conventional chemotherapeutics or radiation therapy. HU is used primarily to treat myeloproliferative diseases because it inhibits the enzyme ribonucleotide reductase involved in DNA synthesis. The hydroxyl group in HU is considered critical for its antiproliferative and chemotherapeutic effects. Here, we substituted the hydroxyl group in HU with a triphenylphosphonium cation attached to an alkyl group with different chain lengths, forming a new class of mitochondria-targeted HU (Mito-HU). Elongating the alkyl side chain length increased the hydrophobicity of Mito-HUs, inhibition of oxidative phosphorylation, and antiproliferative effects in tumor cells. Both mitochondrial complex I- and complex III-induced oxygen consumption decreased with the increasing hydrophobicity of Mito-HUs. The more hydrophobic Mito-HUs also potently inhibited the monocytic myeloid-derived suppressor cells and suppressive neutrophils, and stimulated T cell response, implicating their potential antitumor immunomodulatory mechanism.

| S-EPMC8215227 | biostudies-literature

The gallic acid-phospholipid complex improved the antioxidant potential of gallic acid by enhancing its bioavailability.

Project description:Gallic acid (GA) is well known for its antioxidant and hepatoprotective activity, though its effectiveness is restricted due to rapid metabolism and elimination. To overcome these problems, gallic acid-phospholipid complex was prepared and the effect of phospholipid complexation was investigated on carbon tetrachloride (CCl4)-induced oxidative damage in rat liver. The complex significantly reduced the hepatic marker enzymes in rat serum and restored the antioxidant enzyme levels with respect to CCl4-induced group (P < 0.05 and P < 0.01). Also, the complex improved the pharmacokinetics of GA by increasing the relative bioavailability and elimination half-life. The study therefore suggests that phospholipid complexation has enhanced the therapeutic efficacy of GA which may be due to its improved absorption and increased bioavailability in rat serum.

| S-EPMC3755146 | biostudies-other

Mitochondria-targeted betulinic and ursolic acid derivatives: synthesis and anticancer activity.

Project description:A series of new betulinic and ursolic acid conjugates with a lipophilic triphenylphosphonium cation, meant to enhance the bioavailability and mitochondriotropic action of natural triterpenes, have been synthesized. The in vitro experiments on three human cancer cell lines (MCF-7, HCT-116 and TET21N) revealed that all the obtained triphenylphosphonium triterpene acid derivatives not only showed higher cytotoxicity as compared to betulinic acid but were also markedly superior in triggering mitochondria-dependent apoptosis, as assessed using a range of apoptosis markers such as cytochrome c release, stimulation of caspase-3 activity, and cleavage of poly(ADP-ribose) polymerase, which is one of the targets of caspase 3. The IC50 was much lower for all triphenylphosphonium derivatives when compared to betulinic acid. Out of the tested group of conjugates, the most potent toxicity was exhibited by the betulinic acid conjugate 9 (for 9, the IC50 values against MCF-7 and TET21N cells were 0.70 ?M and 0.74 ?M; for betulinic acid (BA), IC50 > 25 ?M against MCF-7 cells).

| S-EPMC6072465 | biostudies-literature

Penetrating cation/fatty acid anion pair as a mitochondria-targeted protonophore.

Project description:A unique phenomenon of mitochondria-targeted protonophores is described. It consists in a transmembrane H(+)-conducting fatty acid cycling mediated by penetrating cations such as 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) or dodecyltriphenylphosphonium (C(12)TPP). The phenomenon has been modeled by molecular dynamics and directly proved by experiments on bilayer planar phospholipid membrane, liposomes, isolated mitochondria, and yeast cells. In bilayer planar phospholipid membrane, the concerted action of penetrating cations and fatty acids is found to result in conversion of a pH gradient (DeltapH) to a membrane potential (Deltapsi) of the Nernstian value (about 60 mV Deltapsi at DeltapH = 1). A hydrophobic cation with localized charge (cetyltrimethylammonium) failed to substitute for hydrophobic cations with delocalized charge. In isolated mitochondria, SkQ1 and C(12)TPP, but not cetyltrimethylammonium, potentiated fatty acid-induced (i) uncoupling of respiration and phosphorylation, and (ii) inhibition of H(2)O(2) formation. In intact yeast cells, C(12)TPP stimulated respiration regardless of the extracellular pH value, whereas a nontargeted protonophorous uncoupler (trifluoromethoxycarbonylcyanide phenylhydrazone) stimulated respiration at pH 5 but not at pH 3. Hydrophobic penetrating cations might be promising to treat obesity, senescence, and some kinds of cancer that require mitochondrial hyperpolarization.

| S-EPMC2818959 | biostudies-literature

Targeting Methylglyoxal in Diabetic Kidney Disease Using the Mitochondria-Targeted Compound MitoGamide.

Project description:Diabetic kidney disease (DKD) remains the number one cause of end-stage renal disease in the western world. In experimental diabetes, mitochondrial dysfunction in the kidney precedes the development of DKD. Reactive 1,2-dicarbonyl compounds, such as methylglyoxal, are generated from sugars both endogenously during diabetes and exogenously during food processing. Methylglyoxal is thought to impair the mitochondrial function and may contribute to the pathogenesis of DKD. Here, we sought to target methylglyoxal within the mitochondria using MitoGamide, a mitochondria-targeted dicarbonyl scavenger, in an experimental model of diabetes. Male 6-week-old heterozygous Akita mice (C57BL/6-Ins2-Akita/J) or wildtype littermates were randomized to receive MitoGamide (10 mg/kg/day) or a vehicle by oral gavage for 16 weeks. MitoGamide did not alter the blood glucose control or body composition. Akita mice exhibited hallmarks of DKD including albuminuria, hyperfiltration, glomerulosclerosis, and renal fibrosis, however, after 16 weeks of treatment, MitoGamide did not substantially improve the renal phenotype. Complex-I-linked mitochondrial respiration was increased in the kidney of Akita mice which was unaffected by MitoGamide. Exploratory studies using transcriptomics identified that MitoGamide induced changes to olfactory signaling, immune system, respiratory electron transport, and post-translational protein modification pathways. These findings indicate that targeting methylglyoxal within the mitochondria using MitoGamide is not a valid therapeutic approach for DKD and that other mitochondrial targets or processes upstream should be the focus of therapy.

| S-EPMC8145135 | biostudies-literature