Browsing by Subject "MAPK"

Now showing 1 - 12 of 12
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    7,8-Dihydroxiflavone protects adult rat axotomized retinal ganglion cells through MAPK/ERK and PI3K/AKT activation
    (MDPI, 2021-10-08) Galindo Romero, Caridad; Vidal-Villegas, Beatriz; Asís-Martínez, Javier; Lucas Ruiz, Fernando; Gallego Ortega, Alejandro; Vidal Sanz, Manuel; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultad de Óptica y Optometría
    We analyze the 7,8-dihydroxyflavone (DHF)/TrkB signaling activation of two main intracellular pathways, mitogen-activated protein kinase (MAPK)/ERK and phosphatidylinositol 3 kinase (PI3K)/AKT, in the neuroprotection of axotomized retinal ganglion cells (RGCs). Methods: Adult albino Sprague-Dawley rats received left intraorbital optic nerve transection (IONT) and were divided in two groups. One group received daily intraperitoneal DHF (5 mg/kg) and another vehicle (1%DMSO in 0.9%NaCl) from one day before IONT until processing. Additional intact rats were employed as control (n = 4). At 1, 3 or 7 days (d) after IONT, phosphorylated (p)AKT, p-MAPK, and non-phosphorylated AKT and MAPK expression levels were analyzed in the retina by Western blotting (n = 4/group). Radial sections were also immunodetected for the above-mentioned proteins, and for Brn3a and vimentin to identify RGCs and Müller cells (MCs), respectively (n = 3/group). Results: IONT induced increased levels of p-MAPK and MAPK at 3d in DHF- or vehicle-treated retinas and at 7d in DHF-treated retinas. IONT induced a fast decrease in AKT in retinas treated with DHF or vehicle, with higher levels of phosphorylation in DHF-treated retinas at 7d. In intact retinas and vehicle-treated groups, no p-MAPK or MAPK expression in RGCs was observed. In DHF- treated retinas p-MAPK and MAPK were expressed in the ganglion cell layer and in the RGC nuclei 3 and 7d after IONT. AKT was observed in intact and axotomized RGCs, but the signal intensity of p-AKT was stronger in DHF-treated retinas. Finally, MCs expressed higher quantities of both MAPK and AKT at 3d in both DHF- and vehicle-treated retinas, and at 7d the phosphorylation of p-MAPK was higher in DHF-treated groups. Conclusions: Phosphorylation and increased levels of AKT and MAPK through MCs and RGCs in retinas after DHF-treatment may be responsible for the increased and long-lasting RGC protection afforded by DHF after IONT.
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    Aromadendrin alleviates LPS-induced kidney apoptosis and inflammation by inhibiting phosphorylation of MAPK and NF-κB signaling pathways
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Ma, Xiaohong; Liu, Wenhua; Wang, Bin; Shi, Feizhuang
    Background. Excessive inflammation and apoptosis in kidneys are critical players in the pathogenesis of acute kidney injury (AKI). Aromadendrin is a natural flavonoid characterized by anti-inflammatory, anti-apoptotic, and antioxidant actions. Thus, we investigated the roles and mechanisms of aromadendrin in the development of AKI. Methods. Lipopolysaccharide (LPS) was used to induce AKI mice, and one hour after LPS challenge, the mice received oral administration of aromadendrin or vehicle. Renal functions were assessed by measuring blood urea nitrogen and creatinine in serum. Histological changes were determined by hematoxylin and eosin staining. Apoptotic cells of renal tissues were detected by TUNEL staining. Gene expression was measured by western blotting and RT-qPCR. Results. Aromadendrin alleviated LPS-induced renal dysfunctions and histological defects in mice. Additionally, aromadendrin suppressed excessive inflammation and tissue apoptosis in the kidneys of LPS-induced AKI mice. Mechanistically, aromadendrin blocked the activation of NF-κB and MAPK pathways in LPS-induced AKI mice. Conclusion. Aromadendrin alleviates LPS-stimulated inflammation and tissue cell apoptosis in kidneys by inactivating the NF-κB and MAPK pathways
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    Crosstalk between G protein-coupled receptors (GPCRs) and tyrosine kinase receptor (TXR) in the heart after morphine withdrawal
    (2013-12-27) Almela Rojo, Pilar; García-Carmona, Juan-Antonio; Martínez Laorden, Elena; Laorden Carrasco, María Luisa; Milanés Maquilón, María Victoria; Farmacología
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    Differential functional regulation of protein kinase C (PKC) orthologs in fission yeast.
    (AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2017-07) Madrid, M.; Vázquez-Marín, B.; Soto, T.; Franco, A.; Gómez-Gil, E.; Vicente-Soler, J.; Gacto, M.; Pérez, P.; Cansado Vizoso, José; Genética y Microbiología
    The two PKC orthologs Pck1 and Pck2 in the fission yeast Schizosaccharomyces pombe operate in a redundant fashion to control essential functions, including morphogenesis and cell wall biosynthesis, as well as the activity of the cell integrity pathway (CIP) and its core element the MAPK Pmk1. We show here that despite the strong structural similarity and functional redundancy of these two enzymes, the mechanisms regulating their maturation, activation, and stabilization have a remarkably distinct biological impact on both kinases. We found that in contrast to Pck2, putative in vivo phosphorylation of Pck1 within the conserved activation loop, turn and hydrophobic motifs is essential for Pck1 stability and biological functions. Constitutive Pck activation promoted dephosphorylation and destabilization of Pck2, while it enhanced Pck1 levels to interfere with proper downstream signaling to the CIP via Pck2. Importantly, whereas catalytic activity was essential for Pck1 function, Pck2 remained partially functional independently of its catalytic activity. Our findings suggest that early divergence from a common ancestor in fission yeast involved important changes in the mechanisms regulating catalytic activation and stability of PKC family members to allow for flexible and dynamic control of downstream functions, including MAPK signaling.
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    Electroacupuncture preconditioning attenuates acute lung injury in mice through transient receptor potential vanilloid 4-mediated anti-inflammation via inhibiting the p38 MAPK signaling pathway
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2026) Jiangtian Yan; Nina Yin; Wan Liu; Zhigang Wang; Lin Zeng; Biología Celular e Histología
    The objective of this study was to investigate the protective effect of electroacupuncture (EA) preconditioning on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. The changes in inflammatory factors and total protein content in bronchoalveolar lavage fluid (BALF) were quantified using enzyme-linked immunosorbent assay (ELISA) and bicinchoninic acid assay (BCA). Hematoxylin and eosin (H&E) staining was employed to assess the extent of lung injury, while Ly-6G immunohistochemistry was used to examine the infiltration of inflammatory cells. Western blot analysis was employed to detect the expression of TRPV4 and proteins associated with the mitogen-activated protein kinase (MAPK) signaling pathway. In comparison with the sham-operated group, the model group demonstrated an elevated production of inflammatory factors in the BALF, augmented total protein content, elevated lung injury score, increased number of Ly-6G-positive cells, upregulation of TRPV4 expression in the lung, and enhanced p38 phosphorylation. The aforementioned pathological changes were significantly improved by EA preconditioning. Furthermore, the protective effect of EA preconditioning on ALI mice was verified by the use of GSK1016790A, an agonist of TRPV4, which demonstrated that this effect is exerted through the TRPV4-mediated p38 MAPK signaling pathway.
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    ERK1/2, JNK and STAT3 activation and correlation with tumor differentiation in oral SCC
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Gkouveris, I.; Nikitakis, N.; Avgoustidis, D.; Karanikou, M.; Rassidakis, G.; Sklavounou, A.
    Signal transducer and activator of transcription 3 (STAT3) and mitogen activated protein kinases (MAPKs), including ERK and JNK, have been implicated in oral squamous cell carcinoma (OSCC) development and progression. Our purpose was to evaluate the levels of activated STAT3, ERK1/2 and JNK by immunohistochemistry in OSCC and to investigate possible correlations of these molecules with each other as well as with the degree of tumor differentiation. Immunohistochemical assessment of the phosphorylated levels of STAT3(tyrosine/ serine), ERK1/2 and JNK was performed in 60 OSCC, including well, moderately and poorly differentiated tumors. Semiquantitative scoring system was used, by calculating intensity of immunostaining, percentage of positive cells and combined scores. Statistics included Fisher’s test, Student’s T-Test and Kruskal-Wallis analysis, Spearman’s correlation coefficient and multivariate logistic regression analyses. Immunohistochemical levels of both pSTAT3(tyr) and pERK1/2 showed statistically significant differences between well and poorly differentiated tumors with the latter receiving higher mean percentage, intensity and total scores. On the other hand, pJNK showed statistically significantly higher intensity levels in moderately compared to poorly differentiated tumors. pSTAT3(ser) immunoexpression did not appear to correlate with tumor differentiation. Between different molecules, more pronounced, pERK1/2 levels exhibited statistically significant positive correlation with pSTAT3(ser), pSTAT3(tyr) and pJNK expression. ERK1/2 and STAT3 activation (as assessed by tyrosine but not serine phosphorylation) could contribute to a less differentiated phenotype in OSCC, while JNK activation may have an opposite, although possibly less pronounced, effect. Positive correlations between MAPK and STAT3 levels may indicate a direct crosstalk and/or regulation by common upstream pathways.
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    MAPK‑dependent control of mitotic progression in S. pombe
    (BioMed Central, 2024-03-25) Iglesias Romero, Ana Belén; Soto Pino, Teresa; Flor Parra, Ignacio; Salas Pino, Silvia; Ruiz Romero, Gabriel; Gould, Kathleen L.; Cansado Vizoso, José; Daga, Rafael R.; Genética y Microbiología; Facultades de la UMU::Facultad de Biología
    Background: Mitogen-activated protein kinases (MAPKs) preserve cell homeostasis by transducing physicochemical fluctuations of the environment into multiple adaptive responses. These responses involve transcriptional rewiring and the regulation of cell cycle transitions, among others. However, how stress conditions impinge mitotic progression is largely unknown. The mitotic checkpoint is a surveillance mechanism that inhibits mitotic exit in situations of defective chromosome capture, thus preventing the generation of aneuploidies. In this study, we investigate the role of MAPK Pmk1 in the regulation of mitotic exit upon stress. Results: We show that Schizosaccharomyces pombe cells lacking Pmk1, the MAP kinase effector of the cell integrity pathway (CIP), are hypersensitive to microtubule damage and defective in maintaining a metaphase arrest. Epistasis analysis suggests that Pmk1 is involved in maintaining spindle assembly checkpoint (SAC) signaling, and its deletion is additive to the lack of core SAC components such as Mad2 and Mad3. Strikingly, pmk1Δ cells show up to twofold increased levels of the anaphase-promoting complex (APC/C) activator Cdc20Slp1 during unperturbed growth. We demonstrate that Pmk1 physically interacts with Cdc20Slp1 N-terminus through a canonical MAPK docking site. Most important, the Cdc20Slp1 pool is rapidly degraded in stressed cells undergoing mitosis through a mechanism that requires MAPK activity, Mad3, and the proteasome, thus resulting in a delayed mitotic exit. Conclusions: Our data reveal a novel function of MAPK in preventing mitotic exit and activation of cytokinesis in response to stress. The regulation of Cdc20Slp1 turnover by MAPK Pmk1 provides a key mechanism by which the timing of mitotic exit can be adjusted relative to environmental conditions.
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    Metabolic control of cytokinesis by glucose cAMP–PKA signaling in fission yeast
    (Elsevier, 2025-09-19) Marín Castillo, Antonio; León Zaragoza, Sergio; Franco Sánchez, Alejandro; Vicente Soler, Jerónima; Núñez Hernández, Andrés; Soto Pino, Teresa; Madrid Mateo, María Isabel; Cansado Vizoso, José; Genética y Microbiología; Facultades de la UMU::Facultad de Biología
    Cytokinesis, the final step of cell division, must be precisely coordinated with the cellular metabolic status, yet the underlying regulatory mechanisms remain poorly understood. Here we show that in Schizosaccharomyces pombe, glucose signaling promotes cytokinesis via the evolutionarily conserved cAMP–PKA signaling pathway. Loss of the Pka1 catalytic subunit delays assembly and constriction of the contractile actomyosin ring (CAR), whereas constitutive PKA activation enhances CAR integrity and accelerates cytokinesis. Mechanistically, Pka1 downregulates the basal activity of the stress-activated MAPK Sty1 under glucose-rich conditions, thereby stabilizing the formin For3 and its nucleated actin cables, which collaborate to regulate CAR dynamics. Remarkably, cAMP–PKA signaling also facilitates cytokinesis through a parallel, actin cable–independent mechanism. Additionally, mitochondrial respiration contributes to cytokinesis in the presence of glucose through a PKA-independent pathway. These findings reveal a multilayered network that links carbon source metabolism to cytoskeletal organization and underscore the importance of tight PKA activity control for robust cell division.
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    Pilocytic astrocytoma: a review of genetic and molecular factors, diagnostic and prognostic markers
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Bikowska-Opalach, Barbara; Szlufik, Stanisław; Grajkowska, Wiesława; Jozwiak, Jaroslaw
    In spite of numerous studies concerning the pathogenesis of pilocytic astrocytoma (PA), the exact mechanism of the process still remains undetermined. It is difficult to obtain concordance between particular studies, which makes review of existing data especially troublesome. Nevertheless, the most important causative factors seem to be NF1 gene inactivation, in cases related to neurofibromatosis type 1, and BRAF gene overexpression in sporadic PAs, both resulting in MAPK/Erk pathway upregulation. Other molecular alterations, like mTOR or PI3K pathway deregulation, or Matrilin 2 overexpression, may influence the course of the disease, leading to the development of more aggressive and recurrent tumors. In the current paper we review genetic alterations in PA and describe currently studied molecular markers that may contribute to the development of the tumor and can be used in pathological staging of the malformation.
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    Potential role of P2X7 receptor in neurodegenerative processes in a murine model of glaucoma
    (Elsevier, 2019) Pérez de Lara, María J.; Avilés Trigueros, Marcelino; Guzmán-Aránguez, Ana; Valiente Soriano, Francisco Javier; de la Villa, Pedro; Vidal-Sanz, Manuel; Pintor, Jesús; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
    Glaucoma is a common cause of visual impairment and blindness, characterized by retinal ganglion cell (RGC) death. The mechanisms that trigger the development of glaucoma remain unknown and have gained significant relevance in the study of this neurodegenerative disease. P2X7 purinergic receptors (P2X7R) could be involved in the regulation of the synaptic transmission and neuronal death in the retina through different pathways. The aim of this study was to characterize the molecular signals underlying glaucomatous retinal injury. The time-course of functional, morphological, and molecular changes in the glaucomatous retina of the DBA/2J mice were investigated. The expression and localization of P2X7R was analysed in relation with retinal markers. Caspase-3, JNK, and p38 were evaluated in control and glaucomatous mice by immunohistochemical and western-blot analysis. Furthermore, electroretinogram recordings (ERG) were performed to assess inner retina dysfunction. Glaucomatous mice exhibited changes in P2X7R expression as long as the pathology progressed. There was P2X7R overexpression in RGCs, the primary injured neurons, which correlated with the loss of function through ERG measurements. All analyzed MAPK and caspase-3 proteins were upregulated in the DBA/2J retinas suggesting a pro-apoptotic cell death. The increase in P2X7Rs presence may contribute, together with other factors, to the changes in retinal functionality and the concomitant death of RGCs. These findings provide evidence of possible intracellular pathways responsible for apoptosis regulation during glaucomatous degeneration.
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    Research progress on SIRT1 and sepsis.
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2019) Li, Lincheng; Liu, Mingchuan; Cao, Mengyuan; Bai, Xiaozhi
    SIRT1, a member of the sirtuin family, belongs to the NAD + -dependent class III histone deacetylase. SIRT1 can regulate gene expression by catalyzing non-histone and histone lysine residues deacetylation. SIRT1 also plays important roles in glucose and lipid metabolism, cell aging, tumorigenesis and inflammation. Recent studies indicate that SIRT1 can inhibit the inflammatory responses via regulating several inflammatory signaling pathways. It is closely related to the occurrence and development of sepsis and other inflammatory diseases. Research has been done on relevant signaling pathways of SIRT1 as well as its target genes during inflammation. SIRT1 is a hot spot in uncontrolled inflammatory response research. This article focuses on the role of SIRT1 in inflammation, especially its targets and involved signaling pathways in sepsis, and tries to provide more convincing evidence for the clinical treatment of sepsis and other inflammatory diseases.
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    Specific functional features of the cell integrity MAP Kinase pathway in the dimorphic fission yeast Schizosaccharomyces japonicus
    (MDPI, 2021-06-14) Gómez Gil, Elisa; Franco Sánchez, Alejandro; Vázquez Marín, Beatriz; Prieto Ruiz, Francisco; Pérez Díaz, Armando Jesús; Vicente Soler, Jerónima; Madrid Mateo, María Isabel; Soto Pino, Teresa; Cansado Vizoso, José; Genética y Microbiología; Facultades de la UMU::Facultad de Biología
    Mitogen activated protein kinase (MAPK) signaling pathways execute essential functions in eu-karyotic organisms by transducing extracellular stimuli into adaptive cellular responses. In the fis-sion yeast model Schizosaccharomyces pombe the cell integrity pathway (CIP) and its core effector, MAPK Pmk1, play a key role during regulation of cell integrity, cytokinesis, and ionic homeostasis. Schizosaccharomyces japonicus, another fission yeast species, shows remarkable differences with re-spect to S. pombe, including a robust yeast to hyphae dimorphism in response to environmental changes. We show that the CIP MAPK module architecture and its upstream regulators, PKC orthologs Pck1 and Pck2, are conserved in both fission yeast species. However, some of S. pombe’s CIP-related functions, such as cytokinetic control and response to glucose availability, are regulated differently in S. japonicus. Moreover, Pck1 and Pck2 antagonistically regulate S. japonicus hyphal differentiation through fine-tuning of Pmk1 activity. Chimeric MAPK-swapping experiments re-vealed that S. japonicus Pmk1 is fully functional in S. pombe, whereas S. pombe Pmk1 shows a limited ability to execute CIP functions and promote S. japonicus mycelial development. Our findings also suggest that a modified N-lobe domain secondary structure within S. japonicus Pmk1 has a major influence on the CIP signaling features of this evolutionarily diverged fission yeast.2021