Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Molecular Interactions between Neuroglobin and Cytochrome c: Possible Mechanisms of Antiapoptotic Defense in Neuronal Cells.

ABSTRACT: Neuroglobin, which is a heme protein from the globin family that is predominantly expressed in nervous tissue, can promote a neuronal survivor. However, the molecular mechanisms underlying the neuroprotective function of Ngb remain poorly understood to this day. The interactions between neuroglobin and mitochondrial cytochrome c may serve as at least one of the mechanisms of neuroglobin-mediated neuroprotection. Interestingly, neuroglobin and cytochrome c possibly can interact with or without electron transfer both in the cytoplasm and within the mitochondria. This review provides a general picture of molecular interactions between neuroglobin and cytochrome c based on the recent experimental and computational work on neuroglobin and cytochrome c interactions.

SUBMITTER: Semenova MA

PROVIDER: S-EPMC10452090 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Molecular Interactions between Neuroglobin and Cytochrome c: Possible Mechanisms of Antiapoptotic Defense in Neuronal Cells.

Semenova Marina A MA Chertkova Rita V RV Kirpichnikov Mikhail P MP Dolgikh Dmitry A DA

Biomolecules 20230810 8

Neuroglobin, which is a heme protein from the globin family that is predominantly expressed in nervous tissue, can promote a neuronal survivor. However, the molecular mechanisms underlying the neuroprotective function of Ngb remain poorly understood to this day. The interactions between neuroglobin and mitochondrial cytochrome c may serve as at least one of the mechanisms of neuroglobin-mediated neuroprotection. Interestingly, neuroglobin and cytochrome c possibly can interact with ...[more]

PMID: 37627298

Similar Datasets

Investigating molecular interactions between oxidized neuroglobin and cytochrome c.

Project description:The formation of a complex between neuroglobin (Ngb) and cytochrome c (Cyt c) has an important biological role in preventing apoptosis. Binding of Ngb to Cyt c alone is sufficient to block the caspase 9 activation by ferric Cyt c that is released during ischemic insults. Therefore, a detailed information on the Ngb-Cyt c interactions is important for understanding apoptosis. However, the exact nature of the interactions between oxidized human neuroglobin (hNgb) and Cyt c is not well understood. In this work, we used a combination of computational modeling and surface plasmon resonance experiments to obtain and characterize the complex formation between oxidized hNgb and Cyt c. We identified important residues involved in the complex formation, including K72 in Cyt c, which is otherwise known to interact with the apoptotic protease-activation factor-1. Our computational results, together with an optimized structure of the hNgb-Cyt c complex, provide unique insights into how the hNgb-Cyt c complex can abate the apoptotic cascade without an hNgb-Cyt c redox reaction.

| S-EPMC6043506 | biostudies-literature

Cytochrome P450-mediated drug interactions in COVID-19 patients: Current findings and possible mechanisms.

Project description:At the end of 2019, the entire world has witnessed the birth of a new member of coronavirus family in Wuhan, China. Ever since, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has swiftly invaded every corner on the planet. By the end of April 2020, almost 3.5 million cases have been reported worldwide, with a death toll of about 250,000 deaths. It is currently well-recognized that patient's immune response plays a pivotal role in the pathogenesis of Coronavirus Disease 2019 (COVID-19). This inflammatory element was evidenced by its elevated mediators that, in severe cases, reach their peak in a cytokine storm. Together with the reported markers of liver injury, such hyperinflammatory state may trigger significant derangements in hepatic cytochrome P450 metabolic machinery, and subsequent modulation of drug clearance that may result in unexpected therapeutic/toxic response. We hypothesize that COVID-19 patients are potentially vulnerable to a significant disease-drug interaction, and therefore, suitable dosing guidelines with therapeutic drug monitoring should be implemented to assure optimal clinical outcomes.

| S-EPMC7318945 | biostudies-literature

Interactions between neuronal fusion proteins explored by molecular dynamics.

Project description:In this report, we present features of the neuronal SNARE complex determined by atomistic molecular dynamics simulations. The results are robust for three models, varying force fields (AMBER and GROMOS) and solvent environment (explicit and implicit). An excellent agreement with experimental findings is observed. The SNARE core complex behaves like a stiff rod, with limited conformational dynamics. An accurate picture of the interactions within the complex emerges with a characteristic pattern of atomic contacts, hydrogen bonds, and salt bridges reinforcing the underlying layer structure. This supports the metaphor of a molecular Velcro strip that has been used by others to describe the neuronal fusion complex. No evidence for directionality in the formation of these interactions was found. Electrostatics largely dominates all interactions, with an acidic surface patch structuring the hydration layers surrounding the complex. The interactions within the four-helix bundle are asymmetric, with the synaptobrevin R-SNARE notably exhibiting an increased rigidity with respect to the three Q-SNARE helices. The interaction patterns we observe provide a new tool for interpreting the impact of mutations on the complex.

| S-EPMC2292394 | biostudies-literature

Naturally Occurring I81N Mutation in Human Cytochrome c Regulates Both Inherent Peroxidase Activity and Interactions with Neuroglobin.

Project description:Human cytochrome c (hCyt c) is a crucial heme protein and plays an indispensable role in energy conversion and intrinsic apoptosis pathways. The sequence and structure of Cyt c were evolutionarily conserved and only a few naturally occurring mutants were detected in humans. Among those variable sites, position 81 was proposed to act as a peroxidase switch in the initiation stages of apoptosis. In this study, we show that Ile81 not only suppresses the intrinsic peroxidase activity but also is essential for Cyt c to interact with neuroglobin (Ngb), a potential protein partner. The kinetic assays showed that the peroxidase activity of the naturally occurring variant I81N was enhanced up to threefold under pH 5. The local stability of the Ω-loop D (residues 70-85) in the I81N variant was decreased. Moreover, the Alphafold2 program predicted that Ile81 forms stable contact with human Ngb. Meanwhile, the Ile81 to Asn81 missense mutation abolishes the interaction interface, resulting in a ∼40-fold decrease in binding affinity. These observations provide an insight into the structure-function relationship of the conserved Ile81 in vertebrate Cyt c.

| S-EPMC8992277 | biostudies-literature

Novel interactions of CLN5 support molecular networking between Neuronal Ceroid Lipofuscinosis proteins.

Project description:BackgroundNeuronal ceroid lipofuscinoses (NCLs) comprise at least eight genetically characterized neurodegenerative disorders of childhood. Despite of genetic heterogeneity, the high similarity of clinical symptoms and pathology of different NCL disorders suggest cooperation between different NCL proteins and common mechanisms of pathogenesis. Here, we have studied molecular interactions between NCL proteins, concentrating specifically on the interactions of CLN5, the protein underlying the Finnish variant late infantile form of NCL (vLINCLFin).ResultsWe found that CLN5 interacts with several other NCL proteins namely, CLN1/PPT1, CLN2/TPP1, CLN3, CLN6 and CLN8. Furthermore, analysis of the intracellular targeting of CLN5 together with the interacting NCL proteins revealed that over-expression of PPT1 can facilitate the lysosomal transport of mutated CLN5FinMajor, normally residing in the ER and in the Golgi complex. The significance of the novel interaction between CLN5 and PPT1 was further supported by the finding that CLN5 was also able to bind the F1-ATPase, earlier shown to interact with PPT1.ConclusionWe have described novel interactions between CLN5 and several NCL proteins, suggesting a modifying role for these proteins in the pathogenesis of individual NCL disorders. Among these novel interactions, binding of CLN5 to CLN1/PPT1 is suggested to be the most significant one, since over-expression of PPT1 was shown to influence on the intracellular trafficking of mutated CLN5, and they were shown to share a binding partner outside the NCL protein spectrum.

| S-EPMC2790443 | biostudies-literature

Neuronal cytochrome P450 activity and opioid analgesia: relevant sites and mechanisms.

Project description:Recent studies suggest a functional role for neuronal cytochrome P450 monooxygenase (P450) activity in opioid analgesia. To characterize the relevant receptors, brain areas, and circuits, detailed in vitro and in vivo studies were performed with the highly selective μ opioid receptor agonist DAMGO in neuronal P450-deficient mutant (Null) and control mice. Homogenates of brain regions and spinal cord showed no differences in DAMGO-induced activation of [(35)S]- GTPγS binding between Null and control mice, indicating no genotype differences in µ opioid receptor signaling, receptor affinities or receptor densities. Intracerebroventricular (icv) DAMGO produced robust, near-maximal, analgesic responses in control mice which were attenuated by 50% in Null mice, confirming a role for µ opioid receptors in activating P450-associated responses. Intra-periaqueductal gray (PAG) and intra-rostral ventromedial medulla (RVM) injections of DAMGO revealed deficits in Null (vs. control) analgesic responses, yet no such genotype differences were observed after intrathecal DAMGO administration. Taken with earlier published findings, the present results suggest that activation of µ opioid receptors in both the PAG and in the RVM relieves pain by mechanisms which include nerve-terminal P450 enzymes within inhibitory PAG-RVM projections. Spinal opioid analgesia, however, does not seem to require such P450 enzyme activity.

| S-EPMC4464959 | biostudies-literature

Neuroglobin: A New Possible Marker of Estrogen-Responsive Breast Cancer.

Project description:The expression of the α-subtype of Estrogen Receptor (ERα) characterizes most breast cancers (more than 75%), for which endocrine therapy is the mainstay for their treatment. However, a high percentage of ERα+ breast cancers are de novo or acquired resistance to endocrine therapy, and the definition of new targets for improving therapeutic interventions and the prediction of treatment response is demanding. Our previous data identified the ERα/AKT/neuroglobin (NGB) pathway as a common pro-survival process activated in different ERα breast cancer cell lines. However, no in vivo association between the globin and the malignity of breast cancer has yet been done. Here, we evaluated the levels and localization of NGB in ERα+ breast ductal carcinoma tissue of different grades derived from pre-and post-menopausal patients. The results indicate a strong association between NGB accumulation, ERα, AKT activation, and the G3 grade, while no association with the menopausal state has been evidenced. Analyses of the data set (e.g., GOBO) strengthen the idea that NGB accumulation could be linked to tumor cell aggressiveness (high grade) and resistance to treatment. These data support the view that NGB accumulation, mainly related to ER expression and tumor grade, represents a compensatory process, which allows cancer cells to survive in an unfavorable environment.

| S-EPMC8393432 | biostudies-literature

A possible mechanism for redox control of human neuroglobin activity.

Project description:Neuroglobin (Ngb) promotes neuron survival under hypoxic/ischemic conditions. In vivo and in vitro assays provide evidence for redox-regulated functioning of Ngb. On the basis of X-ray crystal structures and our MD simulations, a mechanism for redox control of human Ngb (hNgb) activity via the influence of the CD loop on the active site is proposed. We provide evidence that the CD loop undergoes a strand-to-helix transition when the external environment becomes sufficiently oxidizing, and that this CD loop conformational transition causes critical restructuring of the active site. We postulate that the strand-to-helix mechanics of the CD loop allows hNgb to utilize the lability of Cys46/Cys55 disulfide bonding and of the Tyr44/His64/heme propionate interaction network for redox-controlled functioning of hNgb.

| S-EPMC4114473 | biostudies-literature

Integration Between Cerebral Hemispheres Contributes to Defense Mechanisms.

Project description:Defense mechanisms are mental functions which facilitate coping when real or imagined events challenge personal wishes, needs, and feelings. Whether defense mechanisms have a specific neural basis is unknown. The present research tested the hypothesis that interhemispheric integration plays a critical role in defense mechanism development, by studying a unique sample of patients born without the corpus callosum (agenesis of the corpus callosum; AgCC). Adults with AgCC (N = 27) and matched healthy volunteers (N = 30) were compared on defense mechanism use across increasing levels of developmental maturity (denial, least; projection, intermediate; identification, most). Narratives generated in response to Thematic Apperception Test images were scored according to the Defense Mechanism Manual. Greater use of denial and less identification was found in persons with AgCC, compared to healthy comparisons. This difference emerged after age 18 when full maturation of defenses among healthy individuals was expected. The findings provide clinically important characterization of social and emotional processing in persons with AgCC. More broadly, the results support the hypothesis that functional integration across the hemispheres is important for the development of defense mechanisms.

| S-EPMC7359856 | biostudies-literature

Structural and (Pseudo-)Enzymatic Properties of Neuroglobin: Its Possible Role in Neuroprotection.

Project description:Neuroglobin (Ngb), the third member of the globin family, was discovered in human and murine brains in 2000. This monomeric globin is structurally similar to myoglobin (Mb) and hemoglobin (Hb) α and β subunits, but it hosts a bis-histidyl six-coordinated heme-Fe atom. Therefore, the heme-based reactivity of Ngb is modulated by the dissociation of the distal HisE7-heme-Fe bond, which reflects in turn the redox state of the cell. The high Ngb levels (~100-200 μM) present in the retinal ganglion cell layer and in the optic nerve facilitate the O2 buffer and delivery. In contrast, the very low levels of Ngb (~1 μM) in most tissues and organs support (pseudo-)enzymatic properties including NO/O2 metabolism, peroxynitrite and free radical scavenging, nitrite, hydroxylamine, hydrogen sulfide reduction, and the nitration of aromatic compounds. Here, structural and (pseudo-)enzymatic properties of Ngb, which are at the root of tissue and organ protection, are reviewed, envisaging a possible role in the protection from neuronal degeneration of the retina and the optic nerve.

| S-EPMC8699588 | biostudies-literature