共查询到20条相似文献，搜索用时 343 毫秒
1.
Jia Hao Yeo Chanukya K. Colonne Nuren Tasneem Matthew P. Cosgriff Stuart T. Fraser 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(2):466-471
Background
A healthy human can produce over 1?×?1015 blood cells throughout their life. This remarkable amount of biomass requires a concomitantly vast amount of iron to generate functional haemoglobin and functional erythrocytes.Scope of the review
Erythroblasts form multicellular clusters with macrophages in the foetal liver, bone marrow and spleen termed erythroblastic islands. How the central erythroblastic island macrophage co-ordinates the supply of iron to the developing erythroblasts will be a central focus of this review.Major conclusion
Despite being studied for over 60?years, the mechanisms by which the erythroblastic island niche serves to control erythroid cell iron metabolism are poorly resolved.General significance
Over 2 billion people suffer from some form of anaemia. Iron deficiency anaemia is the most prevalent form of anaemia. Therefore, understanding the processes by which iron is trafficked to, and metabolised in developing erythrocytes, is crucially important. 相似文献2.
Meenakshi Sharma Dinesh Kumar Krishna Mohan Poluri 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(4):924-935
Background
Characterization of partially collapsed protein conformations at atomic level is a daunting task due to their inherent flexibility and conformational heterogeneity. T7 bacteriophage endolysin (T7L) is a single-domain amidase that facilitates the lysis of Gram-negative bacteria. T7L exhibits a pH-dependent structural transition from native state to partially folded (PF) conformation. In the pH range 5–3, T7L PF states display differential ANS binding characteristics.Methods
CD, fluorescence, NMR spectroscopy and lysis assays were used to investigate the structure-stability- dynamics relationships of T7L PF conformations.Results
Structural studies indicated a partial loss of secondary/tertiary structures compared to its native state. The loss in the tertiary structure and the hydrophobic core opening increases upon decrease of pH from 5 to 3. Thermal denaturation experiments delineated that the pH?5 conformation is thermally irreversible in contrast to pH?3, depicting that hydrophobic core opening is essential for thermal reversibility. Further, urea dependent unfolding features of PF state at pH?5 and 4 evidenced for a collapsed conformation at intermediate urea concentrations. Residue level studies revealed that α1-helix and β3-β4 segment of T7L are the major contributors for such a structural collapse and inherent dynamics.Conclusions
The results suggested that the low pH PF states of T7L are heterogeneous and exhibits differential structural, unfolding, thermal reversibility, and dynamic features.General significance
Unraveling the structure-stability characteristics of different endolysin conformations is essential for designing novel chimeric and engineered phage endolysins as broadband antimicrobial agents over a varied pH range. 相似文献3.
Seong-Cheol Park Il Ryong Kim Jin-Young Kim Yongjae Lee Eun-Ji Kim Ji Hyun Jung Young Jun Jung Mi-Kyeong Jang Jung Ro Lee 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(12):2545-2554
Background
It remains an open question whether plant phloem sap proteins are functionally involved in plant defense mechanisms.Methods
The antifungal effects of two profilin proteins from Arabidopsis thaliana, AtPFN1 and AtPFN2, were tested against 11 molds and 4 yeast fungal strains. Fluorescence profiling, biophysical, and biochemical analyses were employed to investigate their antifungal mechanism.Results
Recombinant AtPFN1 and AtPFN2 proteins, expressed in Escherichia coli, inhibited the cell growth of various pathogenic fungal strains at concentrations ranging from 10 to 160?μg/mL. The proteins showed significant intracellular accumulation and cell-binding affinity for fungal cells. Interestingly, the AtPFN proteins could penetrate the fungal cell wall and membrane and act as inhibitors of fungal growth via generation of cellular reactive oxygen species and mitochondrial superoxide. This triggered the AtPFN variant-induced cell apoptosis, resulting in morphological changes in the cells.Conclusion
PFNs may play a critical role as antifungal proteins in the Arabidopsis defense system against fungal pathogen attacks.General significance
The present study indicates that two profilin proteins, AtPFN1 and AtPFN2, can act as natural antimicrobial agents in the plant defense system. 相似文献4.
L. Nadeau D.A. Patten A. Caron L. Garneau E. Pinault-Masson M. Foretz P. Haddad B.G. Anderson L.S. Quinn K. Jardine M.W. McBurney E.E. Pistilli M.E. Harper C. Aguer 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(2):395-407
Background
IL-15 is believed to play a role in the beneficial impact of exercise on muscle energy metabolism. However, previous studies have generally used supraphysiological levels of IL-15 that do not represent contraction-induced IL-15 secretion.Methods
L6 myotubes were treated acutely (3?h) and chronically (48?h) with concentrations of IL-15 mimicking circulating (1–10?pg/ml) and muscle interstitial (100?pg/ml ?20?ng/ml) IL-15 levels with the aim to better understand its autocrine/paracrine role on muscle glucose uptake and mitochondrial function.Results
Acute exposure to IL-15 levels representing muscle interstitial IL-15 increased basal glucose uptake without affecting insulin sensitivity. This was accompanied by increased mitochondrial oxidative functions in association with increased AMPK pathway and formation of complex III-containing supercomplexes. Conversely, chronic IL-15 exposure resulted in a biphasic effect on mitochondrial oxidative functions and ETC supercomplex formation was increased with low IL-15 levels but decreased with higher IL-15 concentrations. The AMPK pathway was activated only by high levels of chronic IL-15 treatment. Similar results were obtained in skeletal muscle from muscle-specific IL-15 overexpressing mice that show very high circulating IL-15 levels.Conclusions
Acute IL-15 treatment that mimics local IL-15 concentrations enhances muscle glucose uptake and mitochondrial oxidative functions. That mitochondria respond differently to different levels of IL-15 during chronic treatments indicates that IL-15 might activate two different pathways in muscle depending on IL-15 concentrations.General significance
Our results suggest that IL-15 may act in an autocrine/paracrine fashion and be, at least in part, involved in the positive effect of exercise on muscle energy metabolism. 相似文献5.
Elisabetta Galbiati Svetlana Avvakumova Alessandra La Rocca Maria Pozzi Silvia Messali Paola Magnaghi Miriam Colombo Davide Prosperi Paolo Tortora 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(10):2254-2260
Background
Vaults are eukaryotic ribonucleoprotein particles composed of up 78 copies of the 97?kDa major vault protein that assembles into a barrel-like, “nanocapsule” enclosing poly(ADP-ribose) polymerase, telomerase-associated protein-1 and small untranslated RNAs. Overall, the molecular mass of vault particles amounts to about 13?MDa. Although it has been implicated in several cellular functions, its physiological roles remain poorly understood. Also, the possibility to exploit it as a nanovector for drug delivery is currently being explored in several laboratories.Methods
Using the baculovirus expression system, vaults were expressed and purified by a dialysis step using a 1?MDa molecular weight cutoff membrane and a subsequent size exclusion chromatography. Purity was assessed by SDS-PAGE, transmission electron microscopy and dynamic light scattering. Particle's endocytic uptake was monitored by flow cytometry and confocal microscopy.Results
The purification protocol here reported is far simpler and faster than those currently available and lead to the production of authentic vault. We then demonstrated its clathrin-mediated endocytic uptake by normal fibroblast and glioblastoma, but not carcinoma cell lines. In contrast, no significant caveolin-mediated endocytosis was detected.Conclusions
These results provide the first evidence for an intrinsic propensity of the vault complex to undergo endocytic uptake cultured eukaryotic cells.General significance
The newly developed purification procedure will greatly facilitate any investigation based on the use of the vault particle as a natural nanocarrier. Its clathrin-mediated endocytic uptake observed in normal and in some tumor cell lines sheds light on its physiological role. 相似文献6.
7.
Francesco Giangreco Siegfried Höfinger Evangelos Bakalis Francesco Zerbetto 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(9):1956-1963
Background
High levels of blood cholesterol are conventionally linked to an increased risk of developing cardiovascular disease (Grundy, 1986). Here we examine the molecular mode of action of natural products with known cholesterol-lowering activity, such as for example the green tea ingredient epigallocatechin gallate and a short pentapeptide, Ile-Ile-Ala-Glu-Lys.Methods
Molecular Dynamics simulations are used to gain insight into the formation process of mixed micelles and, correspondingly, how active agents epigallocatechin gallate and Ile-Ile-Ala-Glu-Lys could possibly interfere with it.Results
Self-assembly of physiological micelles occurs on the order of 35–50?ns; most of the structural properties of mixed micelles are unaffected by epigallocatechin gallate or Ile-Ile-Ala-Glu-Lys which integrate into the micellar surface; the diffusive motion of constituting lipids palmitoyl-oleoyl-phosphatidylcholine and cholesterol is significantly down-regulated by both epigallocatechin gallate and Ile-Ile-Ala-Glu-Lys;Conclusions
The molecular mode of action of natural compounds epigallocatechin gallate and Ile-Ile-Ala-Glu-Lys is a significant down-regulation of the diffusive motion of micellar lipids.General significance
Natural compounds like the green tea ingredient epigallocatechin gallate and a short pentapeptide, Ile-Ile-Ala-Glu-Lys, lead to a significant down-regulation of the diffusive motion of micellar lipids thereby modulating cholesterol absorption into physiological micelles. 相似文献8.
Sumangala Shetty Paul R. Copeland 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(11):2506-2510
Background
Selenoprotein synthesis requires the reinterpretation of a UGA stop codon as one that encodes selenocysteine (Sec), a process that requires a set of dedicated translation factors. Among the mammalian selenoproteins, Selenoprotein P (SELENOP) is unique as it contains a selenocysteine-rich domain that requires multiple Sec incorporation events.Scope of review
In this review we elaborate on new data and current models that provide insight into how SELENOP is made.Major conclusions
SELENOP synthesis requires a specific set of factors and conditions.General significance
As the key protein required for proper selenium distribution, SELENOP stands out as a lynchpin selenoprotein that is essential for male fertility, proper neurologic function and selenium metabolism. 相似文献9.
Yuta Murakami Koichi Takahashi Kyoka Hoshi Hiromi Ito Mayumi Kanno Kiyoshi Saito Kenneth Nollet Yoshiki Yamaguchi Masakazu Miyajima Hajime Arai Yasuhiro Hashimoto Tatsuo Mima 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(8):1835-1842
Background
Spontaneous intracranial hypotension (SIH) is caused by cerebrospinal fluid (CSF) leakage. Definitive diagnosis can be difficult by clinical examinations and imaging studies.Methods
SIH was diagnosed with the following criteria: (i) evidence of CSF leakage by cranial magnetic resonance imaging (MRI) findings of intracranial hypotension and/or low CSF opening pressure; (ii) no recent history of dural puncture. We quantified CSF proteins by ELISA or Western blotting.Results
Comparing with non-SIH patients, SIH patients showed significant increase of brain-derived CSF glycoproteins such as lipocalin-type prostaglandin D synthase (L-PGDS), soluble protein fragments generated from amyloid precursor protein (sAPP) and “brain-type” transferrin (Tf). Serum-derived proteins such as albumin, immunoglobulin G, and serum Tf were also increased. A combination of L-PGDS and brain-type Tf differentiated SIH from non-SIH with sensitivity 94.7% and specificity 72.6%.Conclusion
L-PGDS and brain-type Tf can be biomarkers for diagnosing SIH.General significance
L-PGDS and brain-type Tf biosynthesized in the brain appears to be markers for abnormal metabolism of CSF. 相似文献10.
Yoshito Abe Naoki Odawara Nantanat Aeimhirunkailas Hinako Shibata Naoki Fujisaki Hirofumi Tachibana Tadashi Ueda 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(12):2570-2578
Background
Light chains are abnormally overexpressed from disordered monoclonal B-cells and form amyloid fibrils, which are then deposited on the affected organ, leading to a form of systemic amyloidosis known as AL (Amyloid Light chain) amyloidosis. A green tea catechin, epigallocatechin-3-O-gallate (EGCG), which is thought to inhibit various amyloidoses, is a potent inhibitor of amyloid fibril formation in AL amyloidosis.Methods
An amyloidogenic variable domain in λ6 light chain mutant, Wil was incubated in the presence of EGCG. The incubation products were analyzed by SDS-PAGE and reverse-phase HPLC. The interaction between Wil and EGCG was observed by using NMR and tryptophan fluorescence.Results
EGCG inhibited the amyloid fibril formation of Wil at pH?7.5 and 42?°C. Under these conditions, most Wil populations were in the unfolded state and several chemical reactions, i.e., oxidation and/or covalent bond oligomerization could be induced by auto-oxidated EGCG. Moreover, we found that EGCG bound to the unfolded state of Wil with higher affinity (Kd?=?7?μM).Conclusions
Inhibition of amyloid fibril formation of Wil was caused by 1) EGCG binding to unfolded state rather than folded state and 2) chemical modifications of Wil by auto oxidation of EGCG.General significance
In the competitive formation of amyloid fibrils and off-pathway oligomers, EGCG produces the latter immediately after it preferentially binds to the unfolded state. It may be general mechanism of EGCG inhibition for amyloidosis. 相似文献11.
Petr Herman Aleš Holoubek Barbora Brodska 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(1):266-277
Background
EGFP is a fluorescent tag extensively used in biological and biomedical research. Over the years many researches have gathered collections of cell lines bearing specific EGFP-tagged proteins. Despite its popularity some photochemical properties of EGFP remain undocumented and unused. We report on so far unexplored lifetime photoconversion of EGFP usable in FLIM.Methods
Fluorescence lifetime imaging and spectral FLIM has been used for characterization of the EGFP photoconversion and protein tracking.Result
Our data suggest that EGFP can be permanently photoconverted to a short-fluorescence-lifetime form (PC-EGFP) by intense blue irradiation. PC-EGFP cannot be reverted back by 405?nm light and exhibits the same spectral emission properties with blue-shifted absorption compared to the unconverted EGFP. Fluorescence of PC-EGFP is pH-independent and the photoconversion efficiency decreases with the solvent viscosity. Utilization of the EGFP photoconversion was demonstrated by tracking of a nucleophosmin mutant in live HEK-293?T cells during its cytoplasm-nuclear relocalization induced by Leptomycin B.Conclusions
Besides potential FLIM artifacts caused by an unintended EGFP photoconversion, the controlled photoconversion turns EGFP to an excellent tool for kinetic FLIM applications. Since the photoconversion occurs in the lifetime domain, PC-EGFP can be easily distinguished from the unconverted tag by time-resolved detection while all other spectral channels stay free for multicolor labeling.General significance
The reported lifetime photoconversion lines up EGFP with other photoconvertible fluorescent proteins with special advantage for fluorescence lifetime imaging where lifetime-photoconvertible labels are scarce. 相似文献12.
Greta Jarockyte Dominyka Dapkute Vitalijus Karabanovas Justinas V. Daugmaudis Feliksas Ivanauskas Ricardas Rotomskis 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(4):914-923
Background
Monolayer cell cultures have been considered the most suitable technique for in vivo cellular experiments. However, a lot of cellular functions and responses that are present in natural tissues are lost in two-dimensional cell cultures. In this context, nanoparticle accumulation data presented in literature are often not accurate enough to predict behavior of nanoparticles in vivo. Cellular spheroids show a higher degree of morphological and functional similarity to the tissues.Methods
Accumulation and distribution of carboxylated CdSe/ZnS quantum dots (QDs), chosen as model nanoparticles, was investigated in cellular spheroids composed of different phenotype mammalian cells. The findings were compared with the results obtained in in vivo experiments with human tumor xenografts in immunodeficient mice. The diffusive transport model was used for theoretical nanoparticles distribution estimation.Results
QDs were accumulated only in cells, which were localized in the periphery of cellular spheroids. CdSe/ZnS QDs were shown to be stable and inert; they did not have any side-effects for cellular spheroids formation. Penetration of QDs in both cellular spheroids and in vivo tumor model was limited. The mathematical model confirmed the experimental results: nanoparticles penetrated only 25 μm into cellular spheroids after 24 h of incubation.Conclusions
Penetration of negatively charged nanoparticles is limited not only in tumor tissue, but also in cellular spheroids.General Significance
The results presented in this paper show the superior applicability of cellular spheroids to cell monolayers in the studies of the antitumor effect and penetration of nanomedicines. 相似文献13.
M. Guitart-Mampel A. Gonzalez-Tendero S. Niñerola C. Morén M. Catalán-Garcia I. González-Casacuberta D.L. Juárez-Flores O. Ugarteburu L. Matalonga M.V. Cascajo F. Tort A. Cortés E. Tobias J.C. Milisenda J.M. Grau F. Crispi E. Gratacós G. Garrabou F. Cardellach 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(5):1157-1167
14.
Shuiliang Shi Brian J. Kelly Congrong Wang Ken Klingler Albert Chan George J. Eckert Stephen B. Trippel 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(3):567-575
Background
Insulin-like growth factor I (IGF-I) is a key regulator of chondrogenesis, but its therapeutic application to articular cartilage damage is limited by rapid elimination from the repair site. The human IGF-I gene gives rise to three IGF-I propeptides (proIGF-IA, proIGF-IB and proIGF-IC) that are cleaved to create mature IGF-I. In this study, we elucidate the processing of IGF-I precursors by articular chondrocytes, and test the hypotheses that proIGF-I isoforms bind to heparin and regulate articular chondrocyte biosynthesis.Methods
Human IGF-I propeptides and mutants were overexpressed in bovine articular chondrocytes. IGF-I products were characterized by ELISA, western blot and FPLC using a heparin column. The biosynthetic activity of IGF-I products on articular chondrocytes was assayed for DNA and glycosaminoglycan that the cells produced.Results
Secreted IGF-I propeptides stimulated articular chondrocyte biosynthetic activity to the same degree as mature IGF-I. Of the three IGF-I propeptides, only one, proIGF-IA, strongly bound to heparin. Interestingly, heparin binding of proIGF-IA depended on N-glycosylation at Asn92 in the EA peptide. To our knowledge, this is the first demonstration that N-glycosylation determines the binding of a heparin-binding protein to heparin.Conclusion
The biosynthetic and heparin binding abilities of proIGF-IA, coupled with its generation of IGF-I, suggest that proIGF-IA may have therapeutic value for articular cartilage repair.General significance
These data identify human pro-insulin-like growth factor IA as a bifunctional protein. Its combined ability to bind heparin and augment chondrocyte biosynthesis makes it a promising therapeutic agent for cartilage damage due to trauma and osteoarthritis. 相似文献15.
Sophie Winkler Rupert Derler Bernd Gesslbauer Elmar Krieger Andreas J. Kungl 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(3):528-533
Background
Binding of chemokines to glycosaminoglycans (GAGs) is a crucial step in leukocyte recruitment to inflamed tissues.Methods
A disaccharide compositional analysis of the HS dp6 fraction in combination with MS analysis of the CCL2-depleted dp6 fraction was the basis for target GAG ligand structure suggestions. Four experimentally-derived heparan sulfate hexasaccharides, two potentially chemokine-specific and two unspecific, have been docked to CCL2. Subsequent 300?ns molecular dynamics simulations were used to improve the docked complexes.Results
Hexasaccharides with four sulfations and no acetylations are suggested for selective and high affinity chemokine binding. Using the Antithromin-III/heparin complex as positive control for docking, we were able to recover the correct complex structure only if the previously liganded ATIII structure was used as input. Since the liganded structure is not known for a CCL2-GAG complex, we investigated if molecular dynamics simulations could improve initial docking results. We found that all four GAG oligosaccharides ended up in close contact with the known binding residues after about 100?ns simulation time.Conclusions
A discrimination of specific vs. unspecific CCL2 GAG ligands is not possible by this approach. Long-time molecular dynamics simulations are, however, well suited to capture the delicate enthalpy/entropy balance of GAG binding and improve results obtained from docking.General significance
With the comparison of two methods, MS-based ligand identification and molecular modelling, we have shown the current limitations of our molecular understanding of complex ligand binding which is could be due to the numerical inaccessibility of ligand-induced protein conformational changes. 相似文献16.
Christopher E. Ramsden Marie Hennebelle Susanne Schuster Gregory S. Keyes Casey D. Johnson Irina A. Kirpich Jeff E. Dahlen Mark S. Horowitz Daisy Zamora Ariel E. Feldstein Craig J. McClain Beverly S. Muhlhausler Maria Makrides Robert A. Gibson Ameer Y. Taha 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2018,1863(10):1206-1213
Background
Linoleic acid (LA) is abundant in modern industrialized diets. Oxidized LA metabolites (OXLAMs) and reactive aldehydes, such as 4-hydroxy-2-nonenal (4-HNE), are present in heated vegetable oils and can be endogenously synthesized following consumption of dietary LA. OXLAMs have been implicated in cerebellar degeneration in chicks; 4-HNE is linked to neurodegenerative conditions in mammals. It unknown whether increasing dietary LA or OXLAMs alters the levels of oxidized fatty acids (oxylipins), precursor fatty acids, or 4-HNE in mammalian brain.Objectives
To determine the effects of increases in dietary OXLAMs and dietary LA, on levels of fatty acids, oxylipins, and 4-HNE in mouse brain tissues.Methods
Mice (n?=?8 per group) were fed one of three controlled diets for 8?weeks: (1) a low LA diet, (2) a high LA diet, or (3) the low LA diet with added OXLAMs. Brain fatty acids, oxylipins, and 4-HNE were quantified in mouse cerebellum and cerebral cortex by gas chromatography-flame ionization detection, liquid chromatography-tandem mass spectrometry, and immunoblot, respectively.Results
Increasing dietary LA significantly increased omega-6 fatty acids, decreased omega-3 fatty acids, and increased OXLAMs in brain. Dietary OXLAMs had minimal effect on oxidized lipids but did decrease both omega-6 and omega-3 fatty acids. Neither dietary LA nor OXLAMs altered 4-HNE levels.Conclusion
Brain fatty acids are modulated by both dietary LA and OXLAMs, while brain OXLAMs are regulated by endogenous synthesis from LA, rather than incorporation of preformed OXLAMs. 相似文献17.
Si-Eun Yun Min-Kyung Nam Hyangshuk Rhim 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(7):1602-1611
Background
Regulating apoptosis is a common and essential therapeutic strategy for cancer and neurodegenerative disorders. Based on basic studies of apoptotic mechanisms, various researches have attempted to overcome the pathogenesis of such diseases by activating or inhibiting apoptosis. Generally, the biochemical characteristics of the target molecules should be evaluated along with understanding of their mechanisms of action during drug development. Among apoptotic regulators, XIAP serves as a potent negative regulator to block apoptosis through the inhibition of caspase (CASP)-9 and -3/7. Although XIAP is an attractive target with such apoptotic-modulating property, biochemical and biophysical studies of XIAP are still challenging.Methods
In this study, the CASP-9 and -3/7 inhibitors XIAP, 242Δ and Δ230 were prepared using the pGEX expression system and biochemically characterized.Results
These inhibitors were expressed in Escherichia coli at a concentration of ≥20?mg/L culture under a native condition with 0.01?mM IPTG induction. Notably, using a simple and rapid affinity purification technique, these CASP-9 and -3/7 inhibitors have been purified, yielding ≥5?mg/L culture at approximately 90% purity.Conclusions
We have determined that HtrA2 specifically binds to the BIR2 and BIR3 of XIAP at a 1:1 molecular ratio. Moreover, in vitro cell-free CASP-9 and -3/7 activation-apoptosis assays have demonstrated that these purified XIAP proteins dramatically inhibit CASP-9 and -3/7 action.General significance
Our system is suitable for biochemical studies, such as quantitation of the number of molecules acting on the apoptosis regulation, and provides a basis and insights that can be applied to the development of therapeutic agents for neurodegenerative disorders and cancer. 相似文献18.
Yue Liu James Clement Ross Grant Perminder Sachdev Nady Braidy 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(12):2527-2532
Background
Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that is currently investigated as an important target to extend lifespan and health span. Age-related NAD+ depletion due to the accumulation of oxidative stress is associated with reduced energy production, impaired DNA repair and genomic instability.Scope of review
NAD+ levels can be elevated therapeutically using NAD+ precursors or through lifestyle modifications including exercise and caloric restriction. However, high amounts of NAD+ may be detrimental in cancer progression and may have deleterious immunogenic roles.Major conclusions
Standardized quantitation of NAD+ and related metabolites may therefore represent an important component of NAD+ therapy.General significance
Quantitation of NAD+ may serve dual roles not only as an ageing biomarker, but also as a diagnostic tool for the prevention of malignant disorders. 相似文献19.
20.
Simin Feng Zhuqing Dai Anna B. Liu Jinbao Huang Nihal Narsipur Grace Guo Bo Kong Kenneth Reuhl Wenyun Lu Zisheng Luo Chung S. Yang 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2018,1863(10):1274-1284