DigitalUM :: Browsing by Subject "ROS"

Browsing by Subject "ROS"

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Open Access
1,25-Dihydroxyvitamin D3 mitigates high glucose-induced oxidative stress, inflammation, and extracellular matrix accumulation in glomerular mesangial cells via the ROS/TXNIP/NLRP3 pathway
(2026) Bo Chen; Chunjiang Zhang; Lin Jia; Xingyu Yao; Gang Liu; Qingyue Meng; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e Histiologia
ackground. 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is a physiologically active form of vitamin D. Our study investigated the renoprotective functions of 1,25(OH)2D3 in diabetic nephropathy (DN) progression and its underlying mechanism targeting the ROS/TXNIP/NLRP3 inflammasome pathway. Methods. DN was induced in Wistar rats via high-fat diet (4 weeks) and streptozotocin injection (30 mg/kg, i.p.); hyperglycemic rats were randomized into DN and DN + 1,25(OH)2D3 (16 μg/kg, 12 weeks) groups. Rat mesangial HBZY-1 cells were maintained under normal glucose (5.5 mM), high glucose (25 mM), high glucose plus 1,25(OH)2D3 (1-50 nM), or high glucose plus N acetylcysteine (NAC, 10 mM). Cell viability was assessed by the CCK-8 assay. Oxidative stress parameters (ROS via DCFH-DA fluorescence, MDA content, SOD activity) and pyroptosis markers (LDH release, PI/Hoechst 33342 nuclear staining) were quantified. Renal histopathology was performed using PAS and Masson trichrome staining. Biochemical analyses included serum creatinine, urea nitrogen, and 24h urinary protein quantification. Molecular profiling encompassed ELISA (IL-1β, IL-6, TNF-α, IL-18, fibronectin, collagen IV), RT-qPCR (NOX2, NOX4, NLRP3, ASC), western blotting (TXNIP, NLRP3, ASC, caspase-1, IL-1β, IL-18, collagen IV, fibronectin, laminin), and TXNIP immunofluorescence. Results. 1,25(OH)2D3 significantly attenuated high glucose-induced pathological alterations in HBZY-1 cells, including ROS overproduction, TXNIP upregulation, NLRP3 inflammasome activation, oxidative stress, inflammation, extracellular matrix (ECM) deposition, and pyroptotic cell death. Consistently, 1,25(OH)2D3 suppressed ROS/TXNIP/ NLRP3/caspase-1 signaling, ameliorated renal dysfunction, and mitigated histopathological damage in DN rats. Conclusion. 1,25(OH)2D3 confers renoprotection in DN by inhibiting the ROS/TXNIP/NLRP3 inflamma some axis, thereby suppressing oxidative stress, inflammatory cytokine production, ECM accumulation, and pyroptotic cell death in glomerular mesangial cells and renal tissues.
Open Access
Amygdalin improves ovarian function by inhibiting oxidative stress and inflammation in premature ovarian failure mice
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2026) Jintao Han; Jianyuan Li; Jin Yao; Wenwei Jiang; Biología Celular e Histología
Background. Menstrual stoppage, follicular dysplasia, and hypergonadotropic hypoestrogenism in women under forty are among the symptoms of premature ovarian failure (POF). This study aimed to explore the role and mechanism of amygdalin on ovarian function in a POF mouse model. Methods. A POF mouse model was established via injection of D-galactose (D-gal), followed by amygdalin treatment. Histological staining of ovarian tissues was applied to determine follicular development and granulosa cell apoptosis. Levels of malondialdehyde (MDA), glutathione peroxidase (GSH-px), and superoxide dismutase (SOD) were measured in ovarian tissues. Enzyme-linked immunosorbent assay was used to detect levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E2), anti-Müllerian hormone (AMH), and reactive oxygen species (ROS) in serum, and tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 levels in ovaries. Results. D-gal increased levels of FSH, LH, ROS, MDA, TNF-α, IL-1β, IL-6, Bax, atretic follicles, and granulosa cell apoptosis, and decreased P, E2, AMH, SOD, GSH-px, Bcl-2, and primordial, primary, secondary, and total follicles (p<0.01). Amygdalin with different concentrations reversed the effects of D-gal on mice (p<0.05). Conclusion. Amygdalin improved ovarian function in POF mice through inhibiting oxidative stress, inflammation, and granulosa cell apoptosis. These results suggested that amygdalin may be a potential antioxidant for POF treatment.
Open Access
Fisiología redox: equilibrio entre oxidación, antioxidantes y señalización celular
(2026-05-11) Victoria Montesinos, Desirée ; Mateo Orcajada, Adrián; Fisiología
La fisiología redox estudia el equilibrio entre la producción de especies reactivas, como los radicales libres, y los sistemas antioxidantes del organismo. Estas moléculas no siempre son perjudiciales, ya que en cantidades controladas participan en la señalización celular, la respuesta inmunitaria, la adaptación al ejercicio y la regulación metabólica. Sin embargo, cuando se producen en exceso o fallan los mecanismos antioxidantes, aparece el estrés oxidativo, que puede dañar lípidos, proteínas y ADN. En conjunto, la fisiología redox permite comprender cómo el organismo mantiene el equilibrio oxidativo y protege la función celular.
Open Access
GSTM3, but not IZUMO1, is a cryotolerance marker of boar sperm
(BioMed Central, 2019-08-05) Llavanera, Marc; Delgado-Bermúdez, Ariadna; Fernández-Fuertes, Beatriz; Recuero, Sandra; Mateo, Yentel; Bonet, Sergi; Barranco Cascales, Isabel; Yeste, Marc; Medicina y Cirugía Animal; Facultad de Veterinaria
Background: Cryopreservation is currently the most efficient method for long-term preservation of mammalian gametes and is extensively used in swine artificial insemination (AI) centres. However, it is well-known that cryopreservation procedures induce changes in the water phase in both intra and extracellular compartments, which alter the content and localisation of several proteins and ends up curtailing the structural integrity of functional sperm (i.e., cryoinjuries). Alterations and deficiencies of sperm-oocyte binding proteins during gamete recognition are one of the causes of reproductive failure both in vitro and in vivo. In this sense, characterisation of cryopreservation effects upon oocyte-binding proteins of sperm, such as IZUMO1 and GSTM3, is essential when assessing the impact of this technique in swine reproduction. Results: Cryopreservation was found to induce changes in the localisation of IZUMO1 and GSTM3 in boar sperm. However, the relative content of both proteins was not altered after thawing. Furthermore, whereas IZUMO1 content was found not to be related to the cryotolerance of boar sperm, GSTM3 content was observed to be higher in poor (PFE) than in good (GFE) freezability ejaculates in both pre-frozen (1.00 INT·mm2 ± 0.14 INT·mm2 vs. 0.72 INT·mm2 ± 0.15 INT·mm2; P < 0.05) and post-thawed (0.96 INT·mm2 ± 0.20 INT·mm2 vs. 70 INT·mm2 ± 0.19 INT·mm2; P < 0.05) samples. Moreover, GSTM3 levels were found to be higher in those spermatozoa that exhibited low mitochondrial activity, high reactive oxygen species (ROS) production, and high membrane lipid disorder post-thaw (P < 0.05). Conclusions: The difference in GSTM3 content between GFE and PFE, together with this protein having been found to be related to poor sperm quality post-thaw, suggests that it could be used as a cryotolerance marker of boar spermatozoa. Furthermore, both IZUMO1 and GSTM3 relocate during cryopreservation, which could contribute to the reduced fertilising capacity of frozen-thawed boar sperm.
Open Access
Impact of Seminal Plasma Antioxidants on Donkey Sperm Cryotolerance
(MDPI, 2022-02-18) Catalán, Jaime; Yáñez Ortiz, Iván; Tvarijonaviciute, Asta; González Arostegui, Luis Guillermo; Peres Rubio, Camila; Yeste, Marc; Miró, Jordi; Barranco Cascales, Isabel; Medicina y Cirugía Animal
This study investigated whether the activities of the antioxidant components of donkey seminal plasma (SP)-both enzymatic (superoxide dismutase (SOD), catalase-like (CAT), glutathione peroxidase-like (GPX), and paraoxonase type 1 (PON1)) and non-enzymatic (measured in terms of total thiol, copper-reducing antioxidant capacity (CUPRAC), ferric-reducing ability of plasma (FRAP), and Trolox equivalent antioxidant capacity (TEAC))-and oxidative stress index (OSI) are related to sperm cryotolerance. For this purpose, 15 ejaculates from jackasses (one per individual) were collected and split into two aliquots. The first one was used for measuring the activities levels of enzymatic and non-enzymatic antioxidants and OSI in SP, whereas the other aliquot was cryopreserved. Before cryopreservation, sperm quality parameters (concentration, motility, and viability) were evaluated. After thawing, sperm motility, plasma membrane integrity, lipid disorder, mitochondrial membrane potential, reactive oxygen species (ROS), and calcium intracellular levels were also determined. Based on the percentages of total motility (TM) and of sperm with an intact plasma membrane (SYBR14+/PI-) after thawing, samples were classified as good-freezability (GFE) or poor-freezability (PFE) ejaculates through cluster analyses. The SP activity levels of enzymatic (SOD and PON1) and non-enzymatic antioxidants (CUPRAC, FRAP, and TEAC) were higher (p < 0.05) in GFE than in PFE, whereas SP-OSI was higher (p < 0.05) in PFE than in GFE. In addition, the activity levels of SOD, PON1, GPX, CUPRAC, FRAP, and TEAC were positively (p < 0.05) related to post-thaw sperm motility and plasma membrane integrity and negatively to intracellular ROS levels. The SP-OSI was negatively correlated (p < 0.05) to post-thaw sperm quality parameters and positively to intracellular ROS levels. It can thus be concluded that donkey SP antioxidants are related to sperm cryotolerance and that measurements of antioxidants PON1, SOD, CUPRAC, FRAP, and TEAC, as well as SP-OSI, could be used as markers of sperm cryotolerance. Further research addressing the relationship of these antioxidants and SP-OSI with sperm cryotolerance and their potential use as freezing markers is warranted.
Open Access
NRF3 suppresses the metastasis of triple-negative breast cancer cells by inhibiting ERK activation in a ROS-dependent manner
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Zheng, Chenhui; Pan, Yue; Lin, Bangyi; Li, Jin; Chen, Qi; Zheng, Zhibao
Purpose. Our previous study demonstrated that NRF3 (NFE2L3, Nuclear Factor-erythroid 2-related factor 3) could suppress cell metastasis and proliferation in breast cancer. In this study, we investigated the mechanisms underlying its function in breast cancer. Methods. In the present study, NRF3 expression and its clinical characteristics in breast cancer were analyzed using public datasets and clinical specimens. After breast cancer cells were overexpressed NRF3, FACS was used to detect the intracellular ROS levels. The migration and invasion activities of NRF3-ectopic expressed breast cancer cells were determined by transwell assay. To validate the role of ROS/ERK axis in the inhibitory effect of NRF3 in cell metastasis, ROS scavenger NAC was also included. Results. We found that NRF3 mRNA was highly expressed, while NRF3 protein was extremely lowly expressed in breast cancer tissues compared with their normal counterparts, and low level NRF3 was associated with poorer prognosis in patients with triple negative breast cancer (TNBC). More interestingly, over-expression of NRF3 protein significantly increased cellular ROS production and dramatically decreased p-ERK level and cell migration in TNBC cells. Mechanistically, NRF3 protein was found to be mutually regulated by valosin-containing protein (VCP). Strikingly, VCP-knockdown dramatically increased NRF3 protein expression, but NRF3-knockin also decreased VCP expression in return. Moreover, antioxidant NAC treatment effectively increased the level of p-ERK and VCP expression, as well as cell migration and invasion abilities of TNBC cells. Conclusion. NRF3, a tumor suppressor down-regulated by VCP, could attenuate cell metastasis in TNBC cells by increasing cellular ROS accumulation and subsequently inhibiting the ERK phosphorylation.
Open Access
Rho GTPases and Nox dependent ROS production in skin. Is there a connection?
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Stanley, Alanna; Hynes, Ailish; Brakebusch, Cord; Quondamatteo, Fabio
Rho GTPases are a family of small GTP binding proteins most commonly known for the regulation of many cellular processes, including actin cytoskeleton re-organisation, cell proliferation, signal transduction and regulation of apoptosis. Additionally, a link between Rho GTPases and reactive oxygen species (ROS) has been shown. In line with the growing interest in the role of ROS in cell biology, the relevance of this connection is becoming increasingly clearer. ROS production is classically associated with oxidative metabolic pathways (e.g. respiratory chain, arachidonic acid). During these metabolic pathways, ROS are produced as by-products and these can be potentially toxic. However, numerous cell types contain dedicated enzymatic complexes, i.e., NADPH oxidase (Nox) complexes, for regulated production of ROS. This regulated production of ROS seems to be important for a number of fundamental cell biological processes, including cell growth, differentiation, migration, angiogenesis, aimed at maintaining tissue homeostasis. Data suggests that skin cells are capable of a regulated ROS production via Nox complexes. Members of the Rho GTPase family have been found to play a central regulatory role in Nox activity. In the present review we will focus on the involvement of Rho GTPases in regulated production of ROS with special emphasis on the skin. We will also discuss the possibility that some in vivo effects of the deletion of members of the Rho GTPase family in skin cells could potentially be linked to a reduced ability of regulated ROS production.
Open Access
Sphingosine 1-phosphate and its regulatory role in vascular endothelial cells
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Qiu, Yan; Shen, Junyi; Jiang, Wenli; Yang, Yi; Liu, Xiaoheng; Zeng, Ye
Sphingosine 1-phosphate (S1P) is a bioactive metabolite of sphingomyelin. S1P activates a series of signaling cascades by acting on its receptors S1PR1-3 on endothelial cells (ECs), which plays an important role in endothelial barrier maintenance, anti-inflammation, antioxidant and angiogenesis, and thus is considered as a potential therapeutic biomarker for ischemic stroke, sepsis, idiopathic pulmonary fibrosis, cancers, type 2 diabetes and cardiovascular diseases. We presently review the levels of S1P in those vascular and vascularrelated diseases. Plasma S1P levels were reduced in various inflammation-related diseases such as atherosclerosis and sepsis, but were increased in other diseases including type 2 diabetes, neurodegeneration, cerebrovascular damages such as acute ischemic stroke, Alzheimer's disease, vascular dementia, angina, heart failure, idiopathic pulmonary fibrosis, communityacquired pneumonia, and hepatocellular carcinoma. Then, we highlighted the molecular mechanism by which S1P regulated EC biology including vascular development and angiogenesis, inflammation, permeability, and production of reactive oxygen species (ROS), nitric oxide (NO) and hydrogen sulfide (H2S), which might provide new ways for exploring the pathogenesis and implementing individualized therapy strategies for those diseases
Open Access
The antifungal effect induced by itraconazole in Candida parapsilosis largely depends on the oxidative stress generated at the mitochondria
Muñoz Megías, M. L.; Sanchez-fresneda Pinto, R.; Solano Muñoz, F.; Maicas Prieto, S.; Martínez-Esparza Alvargonzález, María Concepción; Bioquímica y Biología Molecular B e Inmunología
Open Access
The Fungicidal Action of Micafungin is Independent on Both Oxidative Stress Generation and HOG Pathway Signaling in Candida albicans
(MDPI, ) Alonso-Monge, R; Guirao_Abad, JP; Sánchez-Fresneda, R; Pla, J; Yagüe, G; Argüelles, JC; Genética y Microbiología
In fungi, the Mitogen-Activated Protein kinase (MAPK) pathways sense a wide variety of environmental stimuli, leading to cell adaptation and survival. The HOG pathway plays an essential role in the pathobiology of Candida albicans, including the colonization of the gastrointestinal tract in a mouse model, virulence, and response to stress. Here, we examined the role of Hog1 in the C. albicans response to the clinically relevant antifungal Micafungin (MF), whose minimum inhibitory concentration (MIC) was identical in the parental strain (RM100) and in the isogenic homozygous mutant hog1 (0.016 mg/L). The cell viability was impaired without significant differences between the parental strain, the isogenic hog1 mutant, and the Hog1+ reintegrant. This phenotype was quite similar in a collection of hog1 mutants constructed in a different C. albicans background. MF-treated cells failed to induce a relevant increase of both reactive oxygen species (ROS) formation and activation of the mitochondrial membrane potential in parental and hog1 cells. MF was also unable to trigger any significant activation of the genes coding for the antioxidant activities catalase (CAT1) and superoxide dismutase (SOD2), as well as on the corresponding enzymatic activities, whereas a clear induction was observed in the presence of Amphotericin B (AMB), introduced as a positive control of Hog1 signaling. Furthermore, Hog1 was not phosphorylated by the addition of MF, but, notably, this echinocandin caused Mkc1 phosphorylation. Our results strongly suggest that the toxic effect of MF on C. albicans cells is not mediated by the Hog1 MAPK and is independent of the generation of an internal oxidative stress in C. albicans.
Open Access
The visualization of oxidant stress in tissues and isolated cells
(Francisco Hernández, Professor of Cell Biology, University of Murcia, Murcia, Spain, 2000) Frank, J.; Biesalsk, H. K.; Dominici, S.; Pompella, A.
Many studies have implicated the role of oxidant stress in a wide range of human diseases and have led to the rapid expansion of research in this area. With many experimental approaches a direct detection of the production of reactive oxygen species (ROS) and free radicals is not possible. Free radicals are very reactive, short-lived and react in a non-specific way, so that ongoing oxidative damage is generally analyzed by measurement of secondary products e.g. H2O2, "oxidized" proteins, peroxidized lipids and their breakdown products, "oxidized" DNA or by fluorographic analysis in combination with fluorescent dyes e.g. dichlorofluorescin (DCFH). The histochemical visualization of selected molecular markers for oxidative phenomena can often provide valuable information concerning the distribution of oxidative processes in vivo. A number of biochemical methods are available for the monitoring of almost all oxidant stress-related processes, although their applicability in vivo is limited. This review summarizes the biochemical methods currently available for histochemical detection and indirect visualization of an excess of free radicals and ROS. The cited methods are discussed and the results obtained from their application are critically evaluated.
Open Access
TNF induces pathogenic programmed macrophage necrosis in Tuberculosis through a mitochondrial- lysosomal-endoplasmic reticulum circuit
(Cell Press, 2019-08-29) Roca Soler, Francisco José; Whitworth, Laura J.; Redmond, Sarah; Jones, Ana A.; Ramakrishnan, Lalita; Bioquímica y Biología Molecular B e Inmunología
Necrosis of infected macrophages constitutes a critical pathogenetic event in tuberculosis by releasing mycobacteria into the growth-permissive extracellular environment. In zebrafish infected with Mycobacterium marinum or Mycobacterium tuberculosis, excess tumor necrosis factor triggers programmed necrosis of infected macrophages through the production of mitochondrial reactive oxygen species (ROS) and the participation of cyclophilin D, a component of the mitochondrial permeability transition pore. Here, we show that this necrosis pathway is not mitochondrion-intrinsic but results from an inter-organellar circuit initiating and culminating in the mitochondrion. Mitochondrial ROS induce production of lysosomal ceramide that ultimately activates the cytosolic protein BAX. BAX promotes calcium flow from the endoplasmic reticulum into the mitochondrion through ryanodine receptors, and the resultant mitochondrial calcium overload triggers cyclophilin-D-mediated necrosis. We identify ryanodine receptors and plasma membrane L-type calcium channels as druggable targets to intercept mitochondrial calcium overload and necrosis of mycobacterium-infected zebrafish and human macrophages.

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