Abstract:The Cu,Zn superoxide dismutase (SOD1) is an ubiquitary cytosolic dimeric carbohydrate free molecule, belonging to a family of isoenzymes involved in the scavenger of superoxide anions. This effect certainly represents the main and well known function ascribed to this enzyme. Here we highlight new aspects of SOD1 physiology that point out some inedited effects of this enzyme in addition to the canonic role of oxygen radical enzymatic dismutation. In the last two decades our research group produced many data obt… Show more
“…This coincides with molecular results that report a high phosphorylating efficacy on SNAP-25, indicating a good operation of vesicle release to support the high quantal content in presymptomatic stage. However, high Ca 2+ concentrations have been related with apoptosis due to ion imbalance [136,137] and sustained calcium-dependent PKC activation [138]. Indeed, increased levels of adducin, another PKC target that participates in NMJ stabilization, have been found in ALS patients [139], which is another piece of evidence that elevations of Ca 2+ lead to NMJ destabilization.…”
Section: Bdnf/trkb Downstream Protein Kinases and Targets Are Impairementioning
Brain-derived neurotrophic factor (BDNF) promotes neuron survival in adulthood in the central nervous system. In the peripheral nervous system, BDNF is a contraction-inducible protein that, through its binding to tropomyosin-related kinase B receptor (TrkB), contributes to the retrograde neuroprotective control done by muscles, which is necessary for motor neuron function. BDNF/TrkB triggers downstream presynaptic pathways, involving protein kinase C, essential for synaptic function and maintenance. Undeniably, this reciprocally regulated system exemplifies the tight communication between nerve terminals and myocytes to promote synaptic function and reveals a new view about the complementary and essential role of pre and postsynaptic interplay in keeping the synapse healthy and strong. This signaling at the neuromuscular junction (NMJ) could establish new intervention targets across neuromuscular diseases characterized by deficits in presynaptic activity and muscle contractility and by the interruption of the connection between nervous and muscular tissues, such as amyotrophic lateral sclerosis (ALS). Indeed, exercise and other therapies that modulate kinases are effective at delaying ALS progression, preserving NMJs and maintaining motor function to increase the life quality of patients. Altogether, we review synaptic activity modulation of the BDNF/TrkB/PKC signaling to sustain NMJ function, its and other kinases’ disturbances in ALS and physical and molecular mechanisms to delay disease progression.
“…This coincides with molecular results that report a high phosphorylating efficacy on SNAP-25, indicating a good operation of vesicle release to support the high quantal content in presymptomatic stage. However, high Ca 2+ concentrations have been related with apoptosis due to ion imbalance [136,137] and sustained calcium-dependent PKC activation [138]. Indeed, increased levels of adducin, another PKC target that participates in NMJ stabilization, have been found in ALS patients [139], which is another piece of evidence that elevations of Ca 2+ lead to NMJ destabilization.…”
Section: Bdnf/trkb Downstream Protein Kinases and Targets Are Impairementioning
Brain-derived neurotrophic factor (BDNF) promotes neuron survival in adulthood in the central nervous system. In the peripheral nervous system, BDNF is a contraction-inducible protein that, through its binding to tropomyosin-related kinase B receptor (TrkB), contributes to the retrograde neuroprotective control done by muscles, which is necessary for motor neuron function. BDNF/TrkB triggers downstream presynaptic pathways, involving protein kinase C, essential for synaptic function and maintenance. Undeniably, this reciprocally regulated system exemplifies the tight communication between nerve terminals and myocytes to promote synaptic function and reveals a new view about the complementary and essential role of pre and postsynaptic interplay in keeping the synapse healthy and strong. This signaling at the neuromuscular junction (NMJ) could establish new intervention targets across neuromuscular diseases characterized by deficits in presynaptic activity and muscle contractility and by the interruption of the connection between nervous and muscular tissues, such as amyotrophic lateral sclerosis (ALS). Indeed, exercise and other therapies that modulate kinases are effective at delaying ALS progression, preserving NMJs and maintaining motor function to increase the life quality of patients. Altogether, we review synaptic activity modulation of the BDNF/TrkB/PKC signaling to sustain NMJ function, its and other kinases’ disturbances in ALS and physical and molecular mechanisms to delay disease progression.
“…Redox independent actions are also possible. For example, secreted CuZnSOD initiates muscarinic signalling in cholinergic neurons independently of its dismutase activity [43], [44]. Because the actions of redox enzymes, redox-active therapeutics and reactive species are context-dependent, simple partitioning of the redox environment is misleading and is strongly discouraged.Fig.…”
Exercise redox biochemistry is of considerable interest owing to its translational value in health and disease. However, unaddressed conceptual, methodological and technical issues complicate attempts to unravel how exercise alters redox homeostasis in health and disease. Conceptual issues relate to misunderstandings that arise when the chemical heterogeneity of redox biology is disregarded: which often complicates attempts to use redox-active compounds and assess redox signalling. Further, that oxidised macromolecule adduct levels reflect formation and repair is seldom considered. Methodological and technical issues relate to the use of out-dated assays and/or inappropriate sample preparation techniques that confound biochemical redox analysis. After considering each of the aforementioned issues, we outline how each issue can be resolved and provide a unifying set of recommendations. We specifically recommend that investigators: consider chemical heterogeneity, use redox-active compounds judiciously, abandon flawed assays, carefully prepare samples and assay buffers, consider repair/metabolism, use multiple biomarkers to assess oxidative damage and redox signalling.
“…Samples of IL rather showed a more pronounced intracellular localization along with extracellular expression whereas for Eurasian lynx the extracellular staining was predominant. Nevertheless, despite the description of SOD1 being a cytoplasmic enzyme, there are studies, summarized in the review of Mondola et al 41 which described its extracellular secretion. Extracellular SOD1 can activate through its interaction with a receptor cellular pathways 41 .…”
Section: Discussionmentioning
confidence: 99%
“…Nevertheless, despite the description of SOD1 being a cytoplasmic enzyme, there are studies, summarized in the review of Mondola et al 41 which described its extracellular secretion. Extracellular SOD1 can activate through its interaction with a receptor cellular pathways 41 . Potentially, our staining pattern reveals a similar mechanism for feline CL, but this has to be confirmed by future examinations.…”
Corpora lutea (cL) are transient endocrine glands supporting pregnancy by progesterone production. they develop at the site of ovulation from the remaining follicle, are highly metabolically active and undergo distinct, transformative processes during their lifetime. in contrast to other species, cL of lynxes do not regress at the end of cycle, but remain functionally active (persist) for years. Reactive oxygen species (RoS) and anti-oxidative enzymes are described to be important for the functionality of cL. We examined ten anti-oxidative enzymes in fresh and persistent cL of lynxes as well as in domestic cat CL of different luteal stages. The gene expression profiles, especially those of SOD1 and SOD2, showed some remarkable differences between CL stages during non-pregnant and pregnant cycles of domestic cats and between fresh and persistent CL of lynxes. Lynx gene expression profiles of SODs were confirmed by western blot analysis, immunohistochemistry and activity assays. SOD2 was characterized by a conspicuous high expression and enzyme activity exclusively in persistent cL. We suggest that SOD2 is required to detoxify potential elevated superoxide anion levels by producing H 2 o 2 in the physiologically persistent cL. this product might also act as a signaling molecule, securing the cL from apoptosis and insuring long-term luteal cell survival.Corpora lutea (CL) are transient ovarian endocrine glands that are formed at the site of ovulation through transition of cells from the remaining disrupted follicle. By producing progesterone they support pregnancies 1 . These glands are highly metabolically active and undergo distinct, transformative processes 2 during their lifetime of days (e.g. in rats), weeks (e.g. in dogs) 3 or months (elephants) 4 . They pass different stages over formation, development/maintenance and regression; ending in the corpus albicans stage 2 , also described for domestic cat 5 . The latter stage usually confirms the end of a luteal phase. A very particular exception are lynxes, where persistent CL can be found 6-9 that are not pathological as observed for other species like cows 10 . These persistent CL remain functionally active with continuous production of progesterone [11][12][13] . Possibly, this is part of a mechanism controlling the monooestrus in three of four lynx species 6 and/or may be supporting early pregnancies of following cycles by their additional hormone production 14 . The persistence of these CL is confirmed to be several years 6 .Reactive oxygen species (ROS) are a byproduct of steroid hormone production 15 and anti-oxidative enzymes seem to protect the CL against luteolysis and apoptosis during the maintenance stage 16,17 . Furthermore it is described that ROS are elevated during luteal regression and that anti-oxidative enzymes can rescue CL from regression during pregnancy, see for review 16 . In cells, ROS like superoxide radical or hydrogen peroxide are a result of diverse activities. ROS are part in physiologically positive processes like signaling 18 but t...
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