scholarly journals The Role of Serine-Threonine Protein Phosphatase PP2A in Plant Oxidative Stress Signaling—Facts and Hypotheses

2019 ◽  
Vol 20 (12) ◽  
pp. 3028 ◽  
Author(s):  
Csaba Máthé ◽  
Tamás Garda ◽  
Csongor Freytag ◽  
Márta M-Hamvas
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Protein Phosphatase ◽  
Protein Phosphatases ◽  
Crop Improvement ◽  
Regulatory Function ◽  
Future Research ◽  
Stress Signaling ◽  
Ros Signaling ◽  
External Signals

Abiotic and biotic factors induce oxidative stress involving the production and scavenging of reactive oxygen species (ROS). This review is a survey of well-known and possible roles of serine-threonine protein phosphatases in plant oxidative stress signaling, with special emphasis on PP2A. ROS mediated signaling involves three interrelated pathways: (i) perception of extracellular ROS triggers signal transduction pathways, leading to DNA damage and/or the production of antioxidants; (ii) external signals induce intracellular ROS generation that triggers the relevant signaling pathways and (iii) external signals mediate protein phosphorylation dependent signaling pathway(s), leading to the expression of ROS producing enzymes like NADPH oxidases. All pathways involve inactivation of serine-threonine protein phosphatases. The metal dependent phosphatase PP2C has a negative regulatory function during ABA mediated ROS signaling. PP2A is the most abundant protein phosphatase in eukaryotic cells. Inhibitors of PP2A exert a ROS inducing activity as well and we suggest that there is a direct relationship between these two effects of drugs. We present current findings and hypotheses regarding PP2A-ROS signaling connections related to all three ROS signaling pathways and anticipate future research directions for this field. These mechanisms have implications in the understanding of stress tolerance of vascular plants, having applications regarding crop improvement.

Effects of Serine/Threonine Protein Phosphatases on Ion Channels in Excitable Membranes

2000 ◽  
Vol 80 (1) ◽  
pp. 173-210 ◽  
Author(s):  
Stefan Herzig ◽  
Joachim Neumann
Keyword(s):  
Ion Channels ◽  
Protein Phosphatase ◽  
Protein Phosphatases ◽  
Direct Interaction ◽  
Specific Protein ◽  
Biochemical Properties ◽  
Future Research ◽  
Regulatory Subunits ◽  
Phosphatase Inhibitors ◽  
Protein Phosphatase Inhibitors

This review deals with the influence of serine/threonine-specific protein phosphatases on the function of ion channels in the plasma membrane of excitable tissues. Particular focus is given to developments of the past decade. Most of the electrophysiological experiments have been performed with protein phosphatase inhibitors. Therefore, a synopsis is required incorporating issues from biochemistry, pharmacology, and electrophysiology. First, we summarize the structural and biochemical properties of protein phosphatase (types 1, 2A, 2B, 2C, and 3–7) catalytic subunits and their regulatory subunits. Then the available pharmacological tools (protein inhibitors, nonprotein inhibitors, and activators) are introduced. The use of these inhibitors is discussed based on their biochemical selectivity and a number of methodological caveats. The next section reviews the effects of these tools on various classes of ion channels (i.e., voltage-gated Ca2+ and Na+ channels, various K+ channels, ligand-gated channels, and anion channels). We delineate in which cases a direct interaction between a protein phosphatase and a given channel has been proven and where a more complex regulation is likely involved. Finally, we present ideas for future research and possible pathophysiological implications.

scholarly journals Diquat Determines a Deregulation of lncRNA and mRNA Expression in the Liver of Postweaned Piglets

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Jin Wang ◽  
Zhi-xin Li ◽  
Dan-dan Yang ◽  
Pei-qi Liu ◽  
Zhi-qiang Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Performance ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Reduction Process ◽  
Future Research ◽  
Control Group ◽  
Oxidoreductase Activity ◽  
Go Terms ◽  
Porcine Hepatocytes

Oxidative stress is detrimental to animals and can depress the growth performance and regulate the gene expression of animals. However, it remains unclear how oxidative stress regulates the expression of long noncoding RNAs (lncRNAs) and mRNAs. Therefore, the purpose of this article was to explore the profiles of lncRNAs and mRNAs in the liver of piglets under oxidative stress. Here, we constructed a piglet oxidative stress model induced by diquat and evaluated the effects of oxidative stress on the growth performance and antioxidant enzyme activity of piglets. We also used RNA-Seq to examine the global expression of lncRNAs and mRNAs in piglets under oxidative stress. The targets of lncRNAs and mRNAs were enriched in gene ontology (GO) terms and signaling pathways. The results show that the growth performance and activities of antioxidant enzymes were decreased in piglets under oxidative stress. Moreover, eight lncRNAs (6 upregulated and 2 downregulated) and 30 mRNAs (8 upregulated and 22 downregulated) were differentially expressed in the oxidative stress group of piglets compared to the negative control group. According to biological processes in enriched GO terms, the oxoacid metabolic process, intramolecular oxidoreductase activity, and oxidation-reduction process play important roles in oxidative stress. Pathway analysis showed that the signaling pathways involved in insulin and glucose metabolism had a close relationship with oxidative stress. Furtherin vitroexperiments showed that the expression of the upregulated geneGNMTwas significantly increased in primary porcine hepatocytes after diquat stimulation. In contrast, the level of the downregulated geneGCKwas significantly decreased at 12 h in primary porcine hepatocytes after diquat stimulation. Our results expand our knowledge of the lncRNAs and mRNAs transcribed in the livers of piglets under oxidative stress and provide a basis for future research on the molecular mechanisms mediating oxidative stress and tissue damage.

The B56α PP2A B Regulatory Subunit Promotes Mitochondrial PP2A Activity and Supports Etoposide-Induced Cell Death in Human ALL Derived REH Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3358-3358
Author(s):  
Peter P. Ruvolo ◽  
Vivian R. Ruvolo ◽  
Svitlana M. Kurinna
Keyword(s):  
Signaling Pathways ◽  
Okadaic Acid ◽  
Protein Phosphatase ◽  
T Antigen ◽  
Regulatory Subunit ◽  
Stress Signaling ◽  
Over Expression ◽  
Pp2a Activity ◽  
B Subunit ◽  
Reh Cells

Abstract Protein Phosphatase 2A (PP2A) has broad regulatory effects on diverse signaling pathways so it is not surprising that PP2A is emerging as a possible tumor suppressor. The PP2A inhibitor okadaic acid has been found to promote tumors. Cellular transformation caused by viruses has been shown to involve dysregulation of PP2A pathways (e.g. the SV40 small T antigen). Mutations in PP2A subunit genes have been reported in lung cancer and breast cancer. PP2A does have a role in chronic myeloid leukemia (CML) tumorigenesis. While a role for PP2A in CML is emerging, the significance of PP2A signaling pathways in acute lymphoblastic leukemia (ALL) is currently not clear. PP2A has been shown to negatively regulate BCL2 function in human ALL derived REH cells. Considering that BCL2 is a potent anti-apoptotic molecule, a possibility arises that PP2A may regulate chemoresistance in ALL cells via a mechanism involving BCL2. Supporting such a notion, low dose okadaic acid treatment of REH cells results in robust BCL2 phosphorylation and promotes resistance to chemotherapeutic drugs such as etoposide. A difficulty in studying PP2A-mediated signaling is that the enzyme has a multimeric structure. PP2A is a heterotrimer comprising a catalytic subunit (C), a scaffold subunit (A), and a regulatory subunit (B). There are 2 highly homologous isoforms of the A subunit, 2 highly homologous isoforms of the C subunit, and there are 3 major B subunit families (i.e. B55, B56, and PR72) that at present include 21 proteins. Recent studies indicate that PP2A substrate specificity and sub-cellular localization are mediated by the B subunit. Thus PP2A is not a single enzyme but rather a family of protein phosphatase isoforms defined by which B regulatory subunit controls its function. Little is known about the mechanisms regulating B subunit function. It has been found that a ceramide activated mitochondrial PP2A isoform containing the B56 family member B56α acts as the BCL2 phosphatase in REH cells. In the present study, it was found that over-expression of exogenous B56α in REH cells promoted sensitivity to the chemotherapeutic drug etoposide. B56α was found to promote mitochondrial but not nuclear PP2A activity. B56α was found to promote dephosphorylation of PKCα but not PKCε. This finding suggests that regulation of PKC signaling by PP2A is dependent on different B subunits. As PKCα is a physiologic BCL2 kinase, the ability for B56α to control the PP2A isoform that targets both BCL2 and at least one BCL2 kinase suggests PP2A regulation of BCL2 function is multi-tiered. Finally, over-expression of B56α promoted changes in the composition of proteins present in the mitochondrial membranes as determined by 2D gel electrophoresis. A broad range of proteins were shown to be affected by B56α over-expression (mitochondrial proteins varied in size from < 18kd to > 100kd), PP2A stress signaling mediated by B56α may involve a number of targets. These findings suggest that B56α regulation of PP2A stress signaling is complex but an understanding of this process may result in new strategies for the treatment of ALL.

Vitamin E synthetic derivate—TPGS—selectively induces apoptosis in jurkat t cells via oxidative stress signaling pathways: implications for acute lymphoblastic leukemia

APOPTOSIS ◽  
2016 ◽  
Vol 21 (9) ◽  
pp. 1019-1032 ◽  
Author(s):  
Cristian Ruiz-Moreno ◽  
Marlene Jimenez-Del-Rio ◽  
Ligia Sierra-Garcia ◽  
Betty Lopez-Osorio ◽  
Carlos Velez-Pardo
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
Vitamin E ◽  
Acute Lymphoblastic Leukemia ◽  
Signaling Pathways ◽  
Lymphoblastic Leukemia ◽  
Stress Signaling ◽  
Jurkat T Cells

scholarly journals Polyphenols Targeting MAPK Mediated Oxidative Stress and Inflammation in Rheumatoid Arthritis

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6570
Author(s):  
Tapan Behl ◽  
Tanuj Upadhyay ◽  
Sukhbir Singh ◽  
Sridevi Chigurupati ◽  
Amal M. Alsubayiel ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Bone Erosion ◽  
Mapk Signaling ◽  
Future Research ◽  
Pathophysiological Mechanism ◽  
Critical Function ◽  
Research Perspectives

Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disorder, predominantly symmetric, which causes joint inflammation, cartilage degeneration and bone erosion, resulting in deformity and the loss of physical function. Although the management of RA has steadily improved, the pathophysiological mechanism is incompletely elucidated, and therapeutic options are still limited. Due to shortcomings in the efficacy or safety profiles of conventional RA therapies, therapeutic alternatives have been considered. Therefore, natural extracts containing polyphenolic compounds can become promising adjuvant agents for RA global management, due to their antioxidant, anti-inflammatory and apoptotic properties. Polyphenols can regulate intracellular signaling pathways in RA and can generate different immune responses through some key factors (i.e., MAPK, interleukins (ILs 1 and 6), tumor necrosis factor (TNF), nuclear factor light k chain promoter of activated receptor (NF-κB), and c-Jun N-terminal kinases (JNK)). The critical function of the Toll like-receptor (TLR)-dependent mitogen-activating protein kinase (MAPK) signaling pathway in mediating the pathogenic characteristics of RA has been briefly discussed. Oxidative stress can trigger a change in transcription factors, which leads to the different expression of some genes involved in the inflammatory process. This review aims to provide a comprehensive perspective on the efficacy of polyphenols in mitigating RA by inhibiting signaling pathways, suggesting future research perspectives in order to validate their use.

Acute lysine overload provokes marked striatum injury involving oxidative stress signaling pathways in glutaryl-CoA dehydrogenase deficient mice

2019 ◽  
Vol 129 ◽  
pp. 104467 ◽  
Author(s):  
Alexandre Umpierrez Amaral ◽  
Bianca Seminotti ◽  
Janaína Camacho da Silva ◽  
Francine Hehn de Oliveira ◽  
Rafael Teixeira Ribeiro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Stress Signaling ◽  
Deficient Mice
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