scholarly journals Modification of Glyceraldehyde-3-Phosphate Dehydrogenase with Nitric Oxide: Role in Signal Transduction and Development of Apoptosis

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1656
Author(s):  
Vladimir I. Muronetz ◽  
Maria V. Medvedeva ◽  
Irina A. Sevostyanova ◽  
Elena V. Schmalhausen
Keyword(s):  
Nitric Oxide ◽  
Signal Transduction ◽  
Cysteine Residue ◽  
Nuclear Proteins ◽  
Passive Transport ◽  
Carrier Proteins ◽  
Catalytic Cysteine ◽  
Induction Of Apoptosis ◽  
Direct Confirmation

This review focuses on the consequences of GAPDH S-nitrosylation at the catalytic cysteine residue. The widespread hypothesis according to which S-nitrosylation causes a change in GAPDH structure and its subsequent binding to the Siah1 protein is considered in detail. It is assumed that the GAPDH complex with Siah1 is transported to the nucleus by carrier proteins, interacts with nuclear proteins, and induces apoptosis. However, there are several conflicting and unproven elements in this hypothesis. In particular, there is no direct confirmation of the interaction between the tetrameric GAPDH and Siah1 caused by S-nitrosylation of GAPDH. The question remains as to whether the translocation of GAPDH into the nucleus is caused by S-nitrosylation or by some other modification of the catalytic cysteine residue. The hypothesis of the induction of apoptosis by oxidation of GAPDH is considered. This oxidation leads to a release of the coenzyme NAD+ from the active center of GAPDH, followed by the dissociation of the tetramer into subunits, which move to the nucleus due to passive transport and induce apoptosis. In conclusion, the main tasks are summarized, the solutions to which will make it possible to more definitively establish the role of nitric oxide in the induction of apoptosis.

Role of Nitric Oxide-Mediated Signal Transduction in Hypothermia Induced by Intravenous Anesthetics

1997 ◽  
Vol 813 (1 Thermoregulat) ◽  
pp. 818-826 ◽  
Author(s):  
MYLARRAO BANSINATH ◽  
RAJU N. NIVARTHI ◽  
HERMAN TURNDORF
Keyword(s):  
Nitric Oxide ◽  
Signal Transduction ◽  
Intravenous Anesthetics

scholarly journals Crystal structure of peroxiredoxin 3 from Vibrio vulnificus and its implications for scavenging peroxides and nitric oxide

IUCrJ ◽  
2018 ◽  
Vol 5 (1) ◽  
pp. 82-92 ◽  
Author(s):  
Jinsook Ahn ◽  
Kyung Ku Jang ◽  
Inseong Jo ◽  
Hasan Nurhasni ◽  
Jong Gyu Lim ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Nitric Oxide ◽  
Disulfide Bond ◽  
Vibrio Vulnificus ◽  
Cysteine Residue ◽  
Dimeric Interface ◽  
Catalytic Cysteine ◽  
New Type ◽  
Peroxidase Enzymes ◽  
Peroxiredoxin 3

Peroxiredoxins (Prxs) are ubiquitous cysteine-based peroxidase enzymes. Recently, a new type of Prx, VvPrx3, was identified in the pathogenic bacterium Vibrio vulnificus as being important for survival in macrophages. It employs only one catalytic cysteine residue to decompose peroxides. Here, crystal structures of VvPrx3 representing its reduced and oxidized states have been determined, together with an H2O2-bound structure, at high resolution. The crystal structure representing the reduced Prx3 showed a typical dimeric interface, called the A-type interface. However, VvPrx3 forms an oligomeric interface mediated by a disulfide bond between two catalytic cysteine residues from two adjacent dimers, which differs from the doughnut-like oligomers that appear in most Prxs. Subsequent biochemical studies showed that this disulfide bond was induced by treatment with nitric oxide (NO) as well as with peroxides. Consistently, NO treatment induced expression of the prx3 gene in V. vulnificus, and VvPrx3 was crucial for the survival of bacteria in the presence of NO. Taken together, the function and mechanism of VvPrx3 in scavenging peroxides and NO stress via oligomerization are proposed. These findings contribute to the understanding of the diverse functions of Prxs during pathogenic processes at the molecular level.

scholarly journals Examining the Underappreciated Role of S-Acylated Proteins as Critical Regulators of Phagocytosis and Phagosome Maturation in Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Charneal L. Dixon ◽  
Katrina Mekhail ◽  
Gregory D. Fairn
Keyword(s):  
Signal Transduction ◽  
Fatty Acids ◽  
Sulfur Atom ◽  
Cysteine Residue ◽  
Apoptotic Cells ◽  
Membrane Remodeling ◽  
Phagosome Maturation ◽  
Thioester Bond ◽  
Acylated Proteins

Phagocytosis is a receptor-mediated process used by cells to engulf a wide variety of particulates, including microorganisms and apoptotic cells. Many of the proteins involved in this highly orchestrated process are post-translationally modified with lipids as a means of regulating signal transduction, membrane remodeling, phagosome maturation and other immunomodulatory functions of phagocytes. S-acylation, generally referred to as S-palmitoylation, is the post-translational attachment of fatty acids to a cysteine residue exposed topologically to the cytosol. This modification is reversible due to the intrinsically labile thioester bond between the lipid and sulfur atom of cysteine, and thus lends itself to a variety of regulatory scenarios. Here we present an overview of a growing number of S-acylated proteins known to regulate phagocytosis and phagosome biology in macrophages.

GABAAand GABACreceptor antagonists increase retinal cyclic GMP levels through nitric oxide synthase

2003 ◽  
Vol 20 (6) ◽  
pp. 627-637 ◽  
Author(s):  
DOU YU ◽  
WILLIAM D. ELDRED
Keyword(s):  
Nitric Oxide ◽  
Signal Transduction ◽  
Receptor Antagonist ◽  
Cyclic Gmp ◽  
Gaba Receptor ◽  
Signal Transduction Pathway ◽  
Receptor Antagonists ◽  
Cgmp Signal ◽  
Oxide Synthase

The nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signal transduction pathway plays a role in every retinal cell type. Previous studies have shown that excitatory glutamatergic synaptic pathways can increase cGMP-like immunoreactivity (cGMP-LI) in retina through stimulation of NO production, but little is known about the role of synaptic inhibition in the modulation of cGMP-LI. Gamma-amino-n-butyric acid (GABA) plays critical roles in modulating excitatory synaptic pathways in the retina. Therefore, we used GABA receptor antagonists to explore the role of GABAergic inhibitory synaptic pathways on the modulation of the NO/cGMP signal-transduction system. Cyclic GMP immunocytochemistry was used to investigate the effects of the GABA receptor antagonists bicuculline, picrotoxin, and (1,2,5,6-tetrahyropyridin-4-yl) methylphosphinic acid (TPMPA) on levels of cGMP-LI. Cyclic GMP-LI was strongly increased in response to the GABAAreceptor antagonist bicuculline, while the GABACreceptor antagonist TPMPA had little effect on cGMP-LI. The GABAA/GABACreceptor antagonist, picrotoxin, caused a moderate increase in cGMP-LI, which was mimicked by the combination of bicuculline and TPMPA. The nitric oxide synthase inhibitor, S-methyl-L-thiocitrulline (SMTC), blocked the increased cGMP-LI in response to stimulation with either bicuculline or picrotoxin. Treatments with either of the glutamate receptor antagonists (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) partially blocked the increases in cGMP-LI seen in response to bicuculline, but a combination of MK-801 and CNQX completely eliminated these increases. These results suggest that inhibitory synaptic pathways involving both types of GABA receptors work through excitatory glutamatergic receptors to regulate the NO/cGMP signal-transduction pathway in retina.

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