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The SnRK2.10 kinase mitigates the adverse effects of salinity by protecting photosynthetic machinery
Get PDFSNF1-Related protein kinases Type 2 (SnRK2) are plant-specific enzymes widely distributed across the plant kingdom. They are key players controlling abscisic acid (ABA)-dependent and ABA-independent signaling pathways in the plant response to osmotic stress. Here we established that SnRK2.4 and SnRK2.10, ABA-nonactivated kinases, are activated in Arabidopsis thaliana rosettes during the early response to salt stress and contribute to leaf growth retardation under prolonged salinity but act by maintaining different salt-triggered mechanisms. Under salinity, snrk2.10 insertion mutants were impaired in the reconstruction and rearrangement of damaged core and antenna protein complexes in photosystem II (PSII), which led to stronger non-photochemical quenching, lower maximal quantum yield of PSII, and lower adaptation of the photosynthetic apparatus to high light intensity. The observed effects were likely caused by disturbed accumulation and phosphorylation status of the main PSII core and antenna proteins. Finally, we found a higher accumulation of reactive oxygen species (ROS) in the snrk2.10 mutant leaves under a few-day-long exposure to salinity which also could contribute to the stronger damage of the photosynthetic apparatus and cause other deleterious effects affecting plant growth. We found that the snrk2.4 mutant plants did not display substantial changes in photosynthesis. Overall, our results indicate that SnRK2.10 is activated in leaves shortly after plant exposure to salinity and contributes to salt stress tolerance by maintaining efficient photosynthesis and preventing oxidative damage.
Radosław Mazur, Justyna Maszkowska, Anna Anielska-Mazur, Maciej Garstka, Lidia Polkowska-Kowalczyk, Anna Czajkowska, Agnieszka Zmienko, Grazyna Dobrowolska, Anna Kuli
Impact of isoflavone genistein on psoriasis in in vivo and in vitro investigations
Get PDFGenistein is applied worldwide as an alternative medicament for psoriasis (Ps) because of its anti‐ inflammatory activity and perceived beneficial impact on the skin. Hereby, we report our in vivo and
in vitro investigations to supplement scientific research in this area. The reduction of clinical and biochemical scores in mild to moderate Ps patients taking genistein, its safety, good tolerability with no serious adverse events or discontinuations of treatment, no dose‐limiting toxicities, negligible changes in pharmacodynamic parameters and remarkable serum interleukin level alterations
were documented in this study. A certain regression of the Ps phenotype was visible, based on photo‐documented Ps lesion evaluation. Through in vitro experiments, we found that genistein reduced IL‐17A and TNF‐α induced MAPK, NF‐κB, and PI3K activation in normal human epidermal keratinocytes. Moreover, at the mRNA level of genes associated with the early inflammatory response characteristic for Ps (CAMP, CCL20, DEFB4A, PIK3CA, S100A7, and S100A9) and key cellular signalling (MTORC1 and TFEB), we showed that this isoflavone attenuated the increased response of IL‐17A‐
and TNF‐α‐related pathways. This allows us to conclude that genistein is a good candidate for Ps treatment, being attractive for co‐pharmacotherapy with other drugs
Synthesis of Novel Halogenated Heterocycles Based on o-Phenylenediamine and Their Interactions with the Catalytic Subunit of Protein Kinase CK2
Get PDF: Protein kinase CK2 is a highly pleiotropic protein kinase capable of phosphorylating
hundreds of protein substrates. It is involved in numerous cellular functions, including cell viability,
apoptosis, cell proliferation and survival, angiogenesis, or ER-stress response. As CK2 activity is
found perturbed in many pathological states, including cancers, it becomes an attractive target for
the pharma. A large number of low-mass ATP-competitive inhibitors have already been developed,
the majority of them halogenated. We tested the binding of six series of halogenated heterocyclic
ligands derived from the commercially available 4,5-dihalo-benzene-1,2-diamines. These ligand
series were selected to enable the separation of the scaffold effect from the hydrophobic interactions
attributed directly to the presence of halogen atoms. In silico molecular docking was initially applied
to test the capability of each ligand for binding at the ATP-binding site of CK2. HPLC-derived ligand
hydrophobicity data are compared with the binding affinity assessed by low-volume differential
scanning fluorimetry (nanoDSF). We identified three promising ligand scaffolds, two of which have
not yet been described as CK2 inhibitors but may lead to potent CK2 kinase inhibitors. The inhibitory
activity against CK2α and toxicity against four reference cell lines have been determined for eight
compounds identified as the most promising in nanoDSF assay
Dehydro-tocotrienol-β counteracts oxidative-stress-induced diabetes complications in db/db mice.
Get PDFHyperglycemia, hyperlipidemia, and adiposity are the main factors that cause inflammation in type 2 diabetes due to excessive ROS production, leading to late complications. To counteract the effects of increased free radical production, we searched for a compound with effective antioxidant properties that can induce coenzyme Q biosynthesis without affecting normal cellular functions.Tocotrienols are members of the vitamin E family, well-known as efficient antioxidants that are more effective than tocopherols. Deh-T3beta� is a modified form of the naturally occurring tocotrienol-beta�. The synthesis of this compound involves the sequential modification of geranylgeraniol. In this study, we investigated the effects of this compound in different experimental models of diabetes complications.
Deh-T3beta� was found to possess multifaceted capacities. In addition to enhanced wound healing, deh-T3beta� improved kidney and liver functions, reduced liver steatosis, and improved heart recovery after ischemia and insulin sensitivity in adipose tissue in a mice model of type 2 diabetes. Deh-T3�beta exerts these positive effects in several organs of the diabetic mice without reducing the non-fasting blood glucose levels, suggesting that both its antioxidant properties and improvement in mitochondrial
function are involved, which are central to reducing diabetes complications
Simvastatin does not alleviate muscle pathology in a mouse model of Duchenne muscular dystrophy
Get PDFBackground: Duchenne muscular dystrophy (DMD) is an incurable disease, caused by the mutations in the DMD gene, encoding dystrophin, an actin-binding cytoskeletal protein. Lack of functional dystrophin results in muscle weakness, degeneration, and as an outcome cardiac and respiratory failure. As there is still no cure for affected individuals, the pharmacological compounds with the potential to treat or at least attenuate the symptoms of the disease are under constant evaluation. The pleiotropic agents, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known as statins, have been suggested to exert beneficial effects in the mouse model of DMD. On the other hand, they were also reported to induce skeletal-muscle myopathy. Therefore, we decided to verify the hypothesis that simvastatin may be considered a potential therapeutic agent in DMD.
Methods: Several methods including functional assessment of muscle function via grip strength measurement, treadmill test, and single-muscle force estimation, enzymatic assays, histological analysis of muscle damage, gene expression evaluation, and immunofluorescence staining were conducted to study simvastatin-related alterations in the mdx mouse model of DMD.
Results: In our study, simvastatin treatment of mdx mice did not result in improved running performance, grip strength, or specific force of the single muscle. Creatine kinase and lactate dehydrogenase activity, markers of muscle injury, were also unaffected by simvastatin delivery in mdx mice. Furthermore, no significant changes in inflammation, fibrosis, and angiogenesis were noted. Despite the decreased percentage of centrally nucleated myofibers in gastrocnemius muscle after simvastatin delivery, no changes were noticed in other regeneration-related parameters. Of note, even an increased rate of necrosis was found in simvastatin-treated mdx mice.
Conclusion: In conclusion, our study revealed that simvastatin does not ameliorate DMD pathology
Response to a DNA vaccine against the H5N1 virus depending on the chicken line and number of doses
Get PDFBackground
Avian influenza virus infections cause significant economic losses on poultry farms and pose the threat of a possible pandemic outbreak. Routine vaccination of poultry against avian influenza is not recommended in Europe, however it has been ordered in some other countries, and more countries are considering use of the avian influenza vaccine as a component of their control strategy. Although a variety of such vaccines have been tested, most research has concentrated on specific antibodies and challenge experiments.
Methods
We monitored the transcriptomic response to a DNA vaccine encoding hemagglutinin from the highly pathogenic H5N1 avian influenza virus in the spleens of broiler and layer chickens. Moreover, in layer chickens the response to one and two doses of the vaccine was compared.
Results
All groups of birds immunized with two doses of the vaccine responded at the humoral level by producing specific anti-hemagglutinin antibodies. A response to the vaccine was also detected in the spleen transcriptomes. Differential expression of many genes encoding noncoding RNA and proteins functionally connected to the neuroendocrine-immune system was observed in different immunized groups
Regulation of the abundance of Y‑family polymerases in the cell cycle of budding yeast in response to DNA damage
Get PDFY-family DNA polymerases mediate DNA damage tolerance via translesion synthesis (TLS). Because of the intrinsically
error-prone nature of these enzymes, their activities are regulated at several levels. Here, we demonstrate the common regulation of the cellular abundance of Y-family polymerases, polymerase eta (Pol eta), and Rev1, in response to DNA damage at various stages of the cell cycle. UV radiation influenced polymerase abundance more when cells were exposed in S-phase than in G1- or G2-phases. We noticed two opposing effects of UV radiation in S-phase. On one hand, exposure to increasing
doses of UV radiation at the beginning of this phase increasingly delayed S-phase progression. As a result, the accumulation of Pol eta and Rev1, which in nonirradiated yeast is initiated at the S/G2-phase boundary, was gradually shifted into the prolonged S-phase. On the other hand, the extent of polymerase accumulation was inversely proportional to the dose of
irradiation, such that the accumulation was significantly lower after exposure to 80 J/m2 in S-phase than after exposure to 50 J/m2 or 10 J/m2. The limitation of polymerase accumulation in S-phase-arrested cells in response to high UV dose was suppressed upon RAD9 (but not MRC1) deletion. Additionally, hydroxyurea, which activates mainly the Mrc1-dependent checkpoint, did not limit Pol eta or Rev1 accumulation in S-phase-arrested cells. The results show that the accumulation of Y-family TLS polymerases is limited in S-phase-arrested cells due to high levels of DNA damage and suggest a role of the
Rad9 checkpoint protein in this process
Obituary: in memory of Professor Tadeusz Chojnacki (1932–2020)
Get PDFProfessor Tadeusz Chojnacki passed away on June 13, 2020
The role of genetic factors and monocyte-to-osteoclast differentiation in the pathogenesis of Charcot neuroarthropathy
Get PDFAbsorption of Polyunsaturated Fatty Acid (PUFA) Is Related to IgG Blood Levels of Neonatal Pigs during the First 48 Hours Postpartum
Get PDFThe current study is aimed at highlighting the impact of enterally or parenterally applied immunoglobulins (Igs) on
polyunsaturated fatty acid (PUFA) absorption in newborn pigs. Piglets were chosen as the appropriate model since they are
born agammaglobulinemic and any effects of Ig addition can thus be easily monitored. Twenty-one, new born piglets were used
in the study. Plasma levels of PUFAs, ARA, DHA, and EPA dropped (similarly to that seen in human infants) by between 40
and 50% in newborn, unsuckled piglets fed an infant formula for 48 h. However, piglets fed the same infant formula but
supplied with immunoglobulins (Igs) either orally, by feeding piglets with swine or bovine colostrum, or intravenously, by i.u.a.
(intraumbilical artery) infusion of swine or human Ig preparations or swine serum, demonstrated improved growth and PUFA
levels similar to those observed at birth. The significant positive correlation was found between the body weight gain, as well as
levels of ARA and EPA, and plasma immunoglobulins concentration. These results indicate the importance of the presence of Ig
in the blood for appropriate absorption of dietary PUFAs and probably other nutrients in newborn piglets. This may have an
impact on the dietary guidelines for human neonates, especially those born prematurely with low plasma Ig levels, since PUFAs
are important factors for brain development in early life