-
PloS One 2023Black individuals and men are predisposed to an earlier onset and higher prevalence of hypertension, compared with White individuals and women, respectively. Therefore,...
Black individuals and men are predisposed to an earlier onset and higher prevalence of hypertension, compared with White individuals and women, respectively. Therefore, the influence of race and sex on reactive oxygen species (ROS) production and superoxide dismutase (SOD) activity following induced inflammation was evaluated in female and male human umbilical vein endothelial cells (HUVECs) from Black and White individuals. It was hypothesized that HUVECs from Black individuals and male HUVECs would exhibit greater ROS production and impaired SOD activity. Inflammation was induced in HUVEC cell lines (n = 4/group) using tumor necrosis factor-alpha (TNF-α, 50ng/ml). There were no between group differences in ROS production or SOD activity in HUVECs from Black and White individuals, and HUVECs from Black individuals exhibited similar SOD activity at 24hr compared with 4hr of TNF-α treatment (p>0.05). However, HUVECs from White individuals exhibited significantly greater SOD Activity (p<0.05) at 24hr as compared to 4hr in the control condition but not with TNF-α treatment (p>0.05). Female HUVECs exhibited significantly lower ROS production than male HUVECs in the control condition and following TNF-α induced inflammation (p<0.05). Only female HUVECs exhibited significant increases in SOD activity with increased exposure time to TNF-α induced inflammation (p<0.05). HUVECs from White individuals alone exhibit blunted SOD activity when comparing control and TNF-α conditions. Further, compared to female HUVECs, male HUVECs exhibit a pro-inflammatory state.
Topics: Female; Humans; Male; Human Umbilical Vein Endothelial Cells; Reactive Oxygen Species; Tumor Necrosis Factor-alpha; Sex Characteristics; Superoxide Dismutase-1; Inflammation
PubMed: 37792791
DOI: 10.1371/journal.pone.0292112 -
Molecules (Basel, Switzerland) Sep 2023Encapsulation of bioactive compounds in the liposome system provides several advantages, such as enhancing the stability and lowering the toxicity of active compounds....
Encapsulation of bioactive compounds in the liposome system provides several advantages, such as enhancing the stability and lowering the toxicity of active compounds. Coffee berry extract (CBE) has previously been established to have in vitro anti-aging properties and to retard the aging of human skin. The purposes of this study were to encapsulate CBE in nanoliposomes and to assess its stability and in vitro anti-aging potential in human dermal fibroblasts (HDF), as well as in healthy human skin. In the HDF model, anti-aging potential was determined by nitric oxide (NO) and collagenase inhibition assays and a superoxide dismutase (SOD) activity assay, whereas in healthy human skin (in vivo), the skin elasticity and brightness were examined. First, liposomal CBE (L-CBE) was created with a particle size of 117.33 ± 2.91 nm, a polydispersity index (PDI) of 0.36 ± 0.03, and a zeta potential of -56.13 ± 1.87 mV. The percentages of encapsulation efficacy (%EE) and loading efficacy (%LE) were 71.26 ± 3.12% and 2.18 ± 0.18%, respectively. After undergoing a 12-week stability test, the L-CBE retained more phenolic content than the free CBE when stored at 4 °C, room temperature, and 45 °C. Compared to free CBE, the L-CBE demonstrated a more consistent, elevated, and prolonged release of phenolics from the lipid system. In human dermal fibroblasts, L-CBE showed lower toxicity, and at its maximum nontoxic concentration (10 mg/mL), it exhibited slightly higher anti-aging effects than CBE, including NO inhibition, enhanced SOD activity, and anti-collagenase activities. In clinical trials (30 volunteer subjects), none of the participants' skin was irritated when the L-CBE, the CBE, or base creams were applied. After 2 weeks of application, the L-CBE and CBE creams both demonstrated an improvement in skin elasticity and a reduction in melanin levels, and after 4 weeks, L-CBE cream showed a significantly greater improvement in skin elasticity and lightening. The results demonstrate that the encapsulation of the CBE in liposomal systems could increase its stability and skin penetration, reduce its toxicity, and maintain its anti-aging effect, which is powerful enough to be exploited in anti-aging and whitening agents for application in cosmetics and cosmeceuticals.
Topics: Humans; Coffea; Skin; Cosmetics; Aging; Superoxide Dismutase; Liposomes
PubMed: 37836673
DOI: 10.3390/molecules28196830 -
Journal of Cellular and Molecular... Apr 2024SBFI26, an inhibitor of FABP5, has been shown to suppress the proliferation and metastasis of tumour cells. However, the underlying mechanism by which SBFI26 induces...
SBFI26, an inhibitor of FABP5, has been shown to suppress the proliferation and metastasis of tumour cells. However, the underlying mechanism by which SBFI26 induces ferroptosis in breast cancer cells remains largely unknown. Three breast cancer cell lines were treated with SBFI26 and CCK-8 assessed cytotoxicity. Transcriptome was performed on the Illumina platform and verified by qPCR. Western blot evaluated protein levels. Malondialdehyde (MDA), total superoxide dismutase (T-SOD), Fe, glutathione (GSH) and oxidized glutathione (GSSG) were measured. SBFI26 induced cell death time- and dose-dependent, with a more significant inhibitory effect on MDA-MB-231 cells. Fer-1, GSH and Vitamin C attenuated the effects but not erastin. RNA-Seq analysis revealed that SBFI26 treatment significantly enriched differentially expressed genes related to ferroptosis. Furthermore, SBFI26 increased intracellular MDA, iron ion, and GSSG levels while decreasing T-SOD, total glutathione (T-GSH), and GSH levels.SBFI26 dose-dependently up-regulates the expression of HMOX1 and ALOX12 at both gene and protein levels, promoting ferroptosis. Similarly, it significantly increases the expression of SAT1, ALOX5, ALOX15, ALOXE3 and CHAC1 that, promoting ferroptosis while downregulating the NFE2L2 gene and protein that inhibit ferroptosis. SBFI26 leads to cellular accumulation of fatty acids, which triggers excess ferrous ions and subsequent lipid peroxidation for inducing ferroptosis.
Topics: Humans; Triple Negative Breast Neoplasms; Glutathione Disulfide; Ferroptosis; Lipid Peroxidation; Glutathione; Iron; Superoxide Dismutase; Reactive Oxygen Species; Fatty Acid-Binding Proteins
PubMed: 38516826
DOI: 10.1111/jcmm.18212 -
Cancer Gene Therapy Nov 2023Acquired platinum resistance poses a significant therapeutic impediment to ovarian cancer patient care, accounting for more than 200,000 deaths annually worldwide. We...
Acquired platinum resistance poses a significant therapeutic impediment to ovarian cancer patient care, accounting for more than 200,000 deaths annually worldwide. We previously identified that overexpression of the antioxidant superoxide dismutase 1 (SOD1) in ovarian cancer is associated with a platinum-resistant phenotype via conferring oxidative stress resistance against platinum compounds. We further demonstrated that enzymatic inhibition using small-molecule inhibitors or silencing of SOD1 via RNA interference (RNAi) increased cisplatin sensitivity and potency in vitro. We launched this study to explore the potential therapeutic applications of SOD1 silencing in vivo in order to reverse cisplatin resistance using a graphene-based siRNA delivery platform. PEGylated graphene oxide (GO) polyethyleneimine (GO-mPEG) nanoparticle was complexed with SOD1 siRNA. GO-mPEG-siSOD1 exhibited high biocompatibility, siRNA loading capacity, and serum stability, and showed potent downregulation of SOD1 mRNA and protein levels. We further observed that cisplatin and PEI elicited mitochondrial dysfunction and transcriptionally activated the mitochondrial unfolded protein response (UPR) used as a reporter for their respective cytotoxicities. SOD1 silencing was found to augment cisplatin-induced cytotoxicity resulting in considerable tumour growth inhibition in cisplatin-sensitive A2780 and cisplatin-resistant A2780 subcutaneous mouse xenografts. Our study highlights the potential therapeutic applicability of RNAi-mediated targeting of SOD1 as a chemosensitizer for platinum-resistant ovarian cancers.
Topics: Humans; Female; Animals; Mice; Cisplatin; Antineoplastic Agents; RNA Interference; Superoxide Dismutase-1; Graphite; Ovarian Neoplasms; Cell Line, Tumor; Drug Resistance, Neoplasm; Polyethylene Glycols; RNA, Small Interfering; Carcinoma, Ovarian Epithelial; Nanoparticles
PubMed: 37582934
DOI: 10.1038/s41417-023-00659-2 -
Scientific Reports Oct 2023Global warming is a critical challenge limiting crop productivity. Heat stress during cucumber growing stages caused deterioration impacts on the flowering, fruit, and...
Global warming is a critical challenge limiting crop productivity. Heat stress during cucumber growing stages caused deterioration impacts on the flowering, fruit, and yield stages. In this study, "inbred line 1 and hybrid P1 × P2" (heat-tolerant) and "Barracuda" (heat-sensitive) were utilized to determine the heat tolerance in summer season. The heat injury index was used to exhibit the heat tolerance performance. The heat injury index for heat tolerant (HT) genotypes, on leaves (HIIL%) and female flowers (HIIF%), was less than 25 and 15 % in HT, compared to heat sensitive (HS) was more than 75 and 85%, respectively. Moreover, the content of leaf chlorophyll, proline, brassinosteroid (BRs), abscisic acid content (ABA), the activity of catalase (CAT, EC 1.11. 1.6), peroxidase (POD, EC 1.11.1.7) and superoxide dismutase (SOD, EC 1.15.1.1) increased with the heat stress responses in HT plants. Expression pattern analyses of eight genes, related to POD (CSGY4G005180 and CSGY6G015230), SOD (CSGY4G010750 and CSGY1G026400), CAT (CsGy4G025230 and CsGy4G025240), and BR (CsGy6G029150 and CsGy6G004930) showed a significant increase in HT higher than in HS plants. This study furnishes valuable markers for heat tolerance genotypes breeding in cucumber and provides a basis for understanding heat-tolerance mechanisms.
Topics: Cucumis sativus; Thermotolerance; Plant Breeding; Superoxide Dismutase; Heat-Shock Response
PubMed: 37907590
DOI: 10.1038/s41598-023-45163-7 -
Biochemistry. Biokhimiia Aug 2023This review analyzes data available in the literature on the rates, characteristics, and mechanisms of oxygen reduction to a superoxide anion radical at the sites of... (Review)
Review
This review analyzes data available in the literature on the rates, characteristics, and mechanisms of oxygen reduction to a superoxide anion radical at the sites of photosynthetic electron transport chain where this reduction has been established. The existing assumptions about the role of the components of these sites in this process are critically examined using thermodynamic approaches and results of the recent studies. The process of O2 reduction at the acceptor side of PSI, which is considered the main site of this process taking place in the photosynthetic chain, is described in detail. Evolution of photosynthetic apparatus in the context of controlling the leakage of electrons to O2 is explored. The reasons limiting application of the results obtained with the isolated segments of the photosynthetic chain to estimate the rates of O2 reduction at the corresponding sites in the intact thylakoid membrane are discussed.
PubMed: 37758306
DOI: 10.1134/S0006297923080011 -
Plants (Basel, Switzerland) Jul 2023It has been well known for a long time that inert gases, such as xenon (Xe), have significant biological effects. As these atoms are extremely unlikely to partake in... (Review)
Review
It has been well known for a long time that inert gases, such as xenon (Xe), have significant biological effects. As these atoms are extremely unlikely to partake in direct chemical reactions with biomolecules such as proteins, lipids, and nucleic acids, there must be some other mode of action to account for the effects reported. It has been shown that the topology of proteins allows for cavities and hydrophobic pockets, and it is via an interaction with such protein structures that inert gases are thought to have their action. Recently, it has been mooted that the relatively inert gas molecular hydrogen (H) may also have its effects via such a mechanism, influencing protein structures and actions. H is thought to also act via interaction with redox active compounds, particularly the hydroxyl radical (OH) and peroxynitrite (ONOO), but not nitric oxide (NO), superoxide anions (O) or hydrogen peroxide (HO). However, instead of having a direct interaction with H, is there any evidence that these redox compounds can also interact with Xe pockets and cavities in proteins, either having an independent effect on proteins or interfering with the action of inert gases? This suggestion will be explored here.
PubMed: 37514209
DOI: 10.3390/plants12142594 -
Frontiers in Bioscience (Landmark... Sep 2023Extractions of () are shown to have immune modulation, anti-inflammatory and antioxidant properties. However, is also cytotoxic, antiproliferative, and pro-apoptotic ....
BACKGROUND
Extractions of () are shown to have immune modulation, anti-inflammatory and antioxidant properties. However, is also cytotoxic, antiproliferative, and pro-apoptotic . Furthermore, extractions may influence steroidogenesis. Nevertheless, the impact on Leydig cell function has not previously been investigated. As tumor necrosis factor-alpha (TNF-α) is known to cause Leydig cell dysfunction under inflammatory conditions, it is further proposed that extracts may protect against the negative impact of TNF-α on Leydig cells. The aim of the study was to investigate the effect of an aqueous extract () on Leydig cells exposed to TNF-α.
METHODS
Human chorionic gonadotrophin-stimulated TM3 Leydig cells were exposed for 24 h to (a) TNF-α (0.1, 1, 10, 100 ng/mL), (b) (0.01, 0.1, 1, 10, 100 ng/mL), and (c) co-exposure to 10 ng/mL TNF-α and (0.01, 0.1, 1, 10, 100 ng/mL). We analyzed cell viability, cytotoxicity, caspase 3/7 activation, testosterone concentration, and intracellular superoxide.
RESULTS
TNF-α exposure decreased cell viability, increased cytotoxicity, and caspase 3/7, with no significant effect on intracellular superoxide in TM3 Leydig cells. When concentrations of 0.01-10 ng/mL were tested, we observed improved vitality and reduced levels of caspase 3/7. At 100 ng/mL, decreased viability and increased cytotoxicity and caspase 3/7. However, did not affect intracellular superoxide. Furthermore, protected against 10 ng/mL TNF-α-induced cytotoxicity and apoptosis, except at the highest concentration. alone and in co-culture with 10 ng/mL TNF-α increased testosterone at high concentrations.
CONCLUSIONS
In our TM3 Leydig cell model, protected against TNF-α-induced cytotoxicity and early apoptosis, except at the highest experimental concentrations, where it was cytotoxic. These effects were not mediated through a change in intracellular superoxide. Although further investigations are warranted, aqueous may protect against TNF-α-induced Leydig cell dysfunction.
Topics: Male; Humans; Leydig Cells; Tumor Necrosis Factor-alpha; Superoxides; Caspase 3; Testosterone
PubMed: 37796713
DOI: 10.31083/j.fbl2809213 -
Brain Communications 2024Neurological disorders include a variety of conditions, including Alzheimer's disease, motor neuron disease and Parkinson's disease, affecting longevity and quality of... (Review)
Review
Neurological disorders include a variety of conditions, including Alzheimer's disease, motor neuron disease and Parkinson's disease, affecting longevity and quality of life, and their pathogenesis is associated with oxidative stress. Several of the chronic neurodegenerative pathologies of the CNS share some common features, such as oxidative stress, inflammation, synapse dysfunctions, protein misfolding and defective autophagia. Neuroinflammation can involve the activation of mast cells, contributing to oxidative stress, in addition to other sources of reactive oxygen species. Antioxidants can powerfully neutralize reactive oxygen species and free radicals, decreasing oxidative damage. Antioxidant genes, like the manganese superoxide dismutase enzyme, can undergo epigenetic changes that reduce their expression, thus increasing oxidative stress in tissue. Alternatively, DNA can be altered by free radical damage. The epigenetic landscape of these genes can change antioxidant function and may result in neurodegenerative disease. This imbalance of free radical production and antioxidant function increases the reactive oxygen species that cause cell damage in neurons and is often observed as an age-related event. Increased antioxidant expression in mice is protective against reactive oxygen species in neurons as is the exogenous supplementation of antioxidants. Manganese superoxide dismutase requires manganese for its enzymic function. Antioxidant therapy is considered for age-related neurodegenerative diseases, and a new mimetic of a manganese superoxide dismutase, avasopasem manganese, is described and suggested as a putative treatment to reduce the oxidative stress that causes neurodegenerative disease. The aim of this narrative review is to explore the evidence that oxidative stress causes neurodegenerative damage and the role of antioxidant genes in inhibiting reactive oxygen species damage. Can the neuronal environment of oxidative stress, causing neuroinflammation and neurodegeneration, be reduced or reversed?
PubMed: 38214013
DOI: 10.1093/braincomms/fcad356 -
Acta Pharmacologica Sinica Sep 2023Parthanatos is a type of programmed cell death initiated by over-activated poly (ADP-ribose) polymerase 1 (PARP1). Nuclear translocation of apoptosis inducing factor...
TAX1BP1 contributes to deoxypodophyllotoxin-induced glioma cell parthanatos via inducing nuclear translocation of AIF by activation of mitochondrial respiratory chain complex I.
Parthanatos is a type of programmed cell death initiated by over-activated poly (ADP-ribose) polymerase 1 (PARP1). Nuclear translocation of apoptosis inducing factor (AIF) is a prominent feature of parthanatos. But it remains unclear how activated nuclear PARP1 induces mitochondrial AIF translocation into nuclei. Evidence has shown that deoxypodophyllotoxin (DPT) induces parthanatos in glioma cells via induction of excessive ROS. In this study we explored the downstream signal of activated PARP1 to induce nuclear translocation of AIF in DPT-triggered glioma cell parthanatos. We showed that treatment with DPT (450 nM) induced PARP1 over-activation and Tax1 binding protein 1 (TAX1BP1) distribution to mitochondria in human U87, U251 and U118 glioma cells. PARP1 activation promoted TAX1BP1 distribution to mitochondria by depleting nicotinamide adenine dinucleotide (NAD). Knockdown of TAX1BP1 with siRNA not only inhibited TAX1BP1 accumulation in mitochondria, but also alleviated nuclear translocation of AIF and glioma cell death. We demonstrated that TAX1BP1 enhanced the activity of respiratory chain complex I not only by upregulating the expression of ND1, ND2, NDUFS2 and NDUFS4, but also promoting their assemblies into complex I. The activated respiratory complex I generated more superoxide to cause mitochondrial depolarization and nuclear translocation of AIF, while the increased mitochondrial superoxide reversely reinforced PARP1 activation by inducing ROS-dependent DNA double strand breaks. In mice bearing human U87 tumor xenograft, administration of DPT (10 mg· kg ·d, i.p., for 8 days) markedly inhibited the tumor growth accompanied by NAD depletion, TAX1BP1 distribution to mitochondria, AIF distribution to nuclei as well as DNA DSBs and PARP1 activation in tumor tissues. Taken together, these data suggest that TAX1BP1 acts as a downstream signal of activated PARP1 to trigger nuclear translocation of AIF by activation of mitochondrial respiratory chain complex I.
Topics: Humans; Mice; Animals; Apoptosis Inducing Factor; Superoxides; Reactive Oxygen Species; Parthanatos; NAD; Electron Transport; Electron Transport Complex I; Glioma; Neoplasm Proteins; Intracellular Signaling Peptides and Proteins
PubMed: 37186123
DOI: 10.1038/s41401-023-01091-w