Nanoparticle as Signaling Protein Mimic: Robust Structural and Functional Modulation of CaMKII upon Specific Binding to Fullerene C60 Nanocrystals

Miao, Yanyan; Xu, Jing; Shen, Yi; Chen, Liang; Bian, Yunpeng; Hu, Yi; Zhou, Wei; Zheng, Fang; Man, Na; Shen, Yuanyuan; Zhang, Yunjiao; Wang, Ming; Wen, Longping

doi:10.1021/nn501495a

Cited by 53 publications

(33 citation statements)

References 51 publications

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“…In a key study, C 60 fullerenes were shown to act as specific signaling "mimics" (26). Hence, fullerenes were shown to interact with and modulate the function of the Ca 2+ /calmodulin-dependent protein kinase II (CaMKII), a multimeric intracellular serine/threonine kinase central to Ca 2+ signal transduction, in a manner similar to the welldocumented interaction between the NMDA (N-methyl-D-aspartate) receptor subunit NR2B protein and CaMKII (26).…”

Section: Towards a Molecular Nanotoxicologymentioning

confidence: 99%

“…Hence, fullerenes were shown to interact with and modulate the function of the Ca 2+ /calmodulin-dependent protein kinase II (CaMKII), a multimeric intracellular serine/threonine kinase central to Ca 2+ signal transduction, in a manner similar to the welldocumented interaction between the NMDA (N-methyl-D-aspartate) receptor subunit NR2B protein and CaMKII (26). The results from this detailed experimental study thus suggested that an inorganic nanoparticle can act like a cellular signaling protein and underscored the importance of specific interactions between nanoparticles and proteins.…”

Section: Towards a Molecular Nanotoxicologymentioning

confidence: 99%

See 1 more Smart Citation

Keeping it small: towards a molecular definition of nanotoxicology

Gallud

Fadeel

2015

European Journal of Nanomedicine

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Abstract:In this essay, we offer the opinion that engineered nanomaterials are, by definition, materials that can interact with biological systems at the nanoscale, and that this very fact underlies both the promise and the peril of this multifaceted class of materials. Furthermore, nanomaterials are cloaked in host-derived proteins, lipids, or other biomolecules as they enter into a living organism and this so-called bio-corona may impact on subsequent interactions with biological structures. We will explore some examples of nanoscale effects of engineered nanomaterials, and discuss how such interactions may underpin toxicity, and, conversely, how nanoscale interactions may be harnessed for clinical applications, including the use of nanoparticles as drugs per se.Keywords: biological mimicry; cellular nanomachineries; engineered nanomaterials; molecular dynamics simulations; nanomedicine; nanotopographies; nanotoxicology. Life is a nanoscale phenomenonIn their seminal paper published one decade ago, Donaldson et al. (1) proposed that a new subcategory of toxicology -namely nanotoxicology -be defined to specifically address "the special problems likely to be caused by nanoparticles", and the authors suggested that nanotoxicology be considered "a new frontier in particle toxicology". However, one may argue, instead, that nanotoxicology represents a departure from the traditional toxicology of fine and ultrafine particles and fibers. In fact, nanotoxicology may be understood in light of "the interference of engineered nanomaterials with the functions of cellular and extracellular nanomachineries" (2). This view places emphasis on the fact that life (biology) is "a nanoscale phenomenon" (3). Indeed, living organisms are host to a range of dedicated intra-and extracellular nanoscale machines (4) and this, therefore, suggests that specific, size-dependent toxicities may ensue as a result of exposure to engineered nanomaterials. This does not, however, mean that all nanomaterials are inherently toxic (5), or that a nanospecific effect is necessarily detrimental to the host; in fact, the controlled manipulation of biological systems at the nanoscale may very well open up for novel therapeutic approaches. In this essay, we will explore both sides of the coin. The right size in nanotoxicologyIn his review on "the 'right' size in nanobiotechnology", Whitesides argued that "small" -both nano and micromust be a part of the future of biotechnology; which size is most important depends on what question one is asking (6). Surprisingly, in the field of nanotoxicology, the question of size, and more specifically, how one should define a nanomaterial (indeed, whether or not one should define nanomaterials in the first place) remains a matter of debate. Hence, while some have argued that we should not define nanomaterials, or to be more precise, that a 'one-size-fitsall' definition of nanomaterials will fail to capture what is important for addressing risk (7), others have stated that a definition of nanomaterials for regulatory ...

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Section: Towards a Molecular Nanotoxicologymentioning

confidence: 99%

Section: Towards a Molecular Nanotoxicologymentioning

confidence: 99%

Keeping it small: towards a molecular definition of nanotoxicology

Gallud

Fadeel

2015

European Journal of Nanomedicine

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“…НаноC60 модулиру-ет Ca 2+ /кальмодулинзависимую протеинкиназу II (CaMKII), мультимерную внутриклеточную серин/ треонинспецифичную протеинкиназу, необходимую для трансдукции сигнала Ca 2+ , конкурируя со взаи-модействием субъединицы рецептора NMDA NR2B и CaMKII [48]. Способность наноC60 поддерживать киназную активность CaMKII может в перспективе оказаться полезной для терапевтического исполь-зования фуллерена C 60 .…”

Section: фуллерен и биологические молекулыunclassified

Biological activity of fullerenes - reality and prospects

Dumpis

Анатольевна²,

Nikolayev

et al. 2018

Rev Clin Pharm Drug Ther

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Особое место среди наноструктур занимают фул-лерены. Это связано с тем, что они, и только они, представляют собой молекулярную форму углерода. Следовательно, как и всякие молекулы, они харак-теризуются молекулярной массой и стабильностью состава. Наиболее легко получается и поэтому ши-роко используется наименьший по размеру фулле-рен С 60 , затем фуллерен С 70 . Среди других выде-ленных и хоть минимально изученных фуллеренов можно упомянуть С 74 , С 76 , С 78 , С 80 , С 82 и С 84 и т. д.Биологические свойства представителей любого класса соединений определяются их физическими и химическими свойствами. Однако это не совсем так в приложении к наноструктурам углерода во- Резюмее.В обзоре рассмотрены свойства фуллере-нов и их производных и возможность их применения в биологии и медицине. Фуллерены могут оказывать в биологических системах как антиоксидантное дей-ствие, улавливая активные формы кислорода (АФК), так и окислительное, придавая фуллерену фотосенси-тизирующие свойства. Обладающие мембранотропным действием, липофильные молекулы фуллеренов взаимо-действуют с различными биологическими структурами и могут изменять функции этих структур, увеличивая липофильность активной молекулы (аминокислот, ну-клеиновых кислот, белков и др.). Приведены данные о биологическом действии фуллеренов в опытах in vitro и in vivo. Рассмотрены примеры адресной доставки извест ных терапевтических агентов. Ключевые слова:фуллерен; антиоксидант; фото-сенситизатор; тераностик. BioLogiCAL ACtivity of fuLLErEnEs -rEALity And ProsPECts

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“…For example, nano-C 60 can interact with and modulate the function of Ca 2+ /calmodulin-dependent protein kinase II (CaMKII), a multimeric intracellular serine/threonine-specific kinase central to Ca 2+ signal transduction, by a mechanism that competes with the well-documented interaction between the NMDA receptor subunit NR2B and CaMKII. 287 The example of specific interaction between nanoparticles and cellular signalling proteins may have significant implications for the potential therapeutic applications of fullerene C 60 .…”

Section: Iii3 Biomedical Applicationsmentioning

confidence: 99%