In vitro effect of silver nanoparticles on creatine kinase activity

Abstract

A nanopartícula de prata (AgN) é um dos mais proeminentes nanoprodutos, uma vez que a prata exibe propriedades físicas, químicas e biológicas notavelmente incomuns. Creatina quinase (CK) desempenha um papel central no metabolismo de tecidos que consomem muita energia, tais como o cérebro, músculo esquelético e coração, funcionando como um efetivo sistema tampão dos níveis de ATP celular. Uma diminuição na atividade da CK pode alterar a homeostase energética, contribuindo para a morte celular. No presente trabalho nós estudamos o efeito in vitro de AgN na atividade da CK de cérebro, coração e músculo esquelético de ratos. Nossos resultados demonstraram que AgN (10, 25 e 50 mg L -1 ) in vitro inibiram a atividade da CK em cérebro e músculo esquelético, porém não em coração. Vários trabalhos mostraram que os efeitos citotóxicos da AgN provavelmente envolvem a interação entre íons prata e grupos sulfidrila de proteínas. Nós sugerimos que a AgN inibiu a atividade da CK por meio da interação com grupos tiol da enzima.One of the most prominent nanoproducts is the silver nanoparticle (AgN), since silver ions exhibit remarkably unusual physical, chemical and biological properties. Creatine kinase (CK) plays a central role in metabolism of high-energy consuming tissues such as brain, skeletal muscle and heart, where it functions as an effective buffering system of cellular ATP levels. A decrease of CK activity may impair energy homeostasis, contributing to cell death. In the present work we studied the in vitro effect of AgN on the activity of CK from rat brain, heart and skeletal muscle. Our results demonstrated that AgN (10, ) in vitro inhibited CK from brain and skeletal muscle, but not from heart. Several works showed that AgN cytotoxic effects probably involve interaction between silver ions and sulphydryl groups of proteins. We suggest that AgN inhibited CK activity through interactions with thiol groups of the enzyme.Keywords: silver nanoparticles, creatine kinase, brain, heart, skeletal muscle IntroductionMedicinal inorganic chemistry is a discipline of growing significance in both therapeutic and diagnostic medicine. Inorganic compounds have been used in medicine in an empirical way with little attempt to design the compounds to be used. The design of new biologically active compounds involves the control of toxicity and the target of the metal to specific tissues, organs, or cells.1 The current array of successful metallopharmaceuticals includes platinum anticancer drugs, radio diagnostic agents and others.2 Thus, biomedical inorganic chemistry offers the potential for the design of novel therapeutic and diagnostic agents and for the treatment and understanding of diseases. 3Nanotechnology involves the creation and manipulation of materials at nanoscale levels and is a promising field for generating new applications in medicine. [4][5][6][7][8] One of the most prominent nanoproducts are silver nanoparticles Paula et al. 1557 Vol. 20, No. 8, 2009 (AgN), since silver exhibits remarkably unusual physical, chemic...

Macrophage inflammatory and metabolic responses to graphene-based nanomaterials differing in size and functionalization

“…Interestingly, the inhibitory effect of nanomaterials towards this enzyme has been previously reported for brain and skeletal muscle CK exposed to silver nanoparticles. 56 Finally, we also noticed prominent variations in choline-containing metabolites (Figure 5B). Phosphocholine increased upon exposure to LPS or to PG-FMN (S), and an additional strong increase in glycerophosphocholine was noticed in LPS-treated macrophages.…”

Protein corona-induced modification of silver nanoparticle aggregation in simulated gastric fluid

“…Interestingly, Ag + ions have been shown to preferentially interact with sulfhydryl groups in the cysteine residues of proteins and can subsequently inhibit enzymatic activity. 68, 69 However, the decrease in activity due to Ag + ions is less than for all AgNPs, suggesting that interaction with the sulfhydryl groups does not have as large of an effect on activity as binding to the nanoparticle within the protein corona. Overall, the results indicates that the AgNPs have a greater inhibitory effect on pepsin catalytic activity than Ag + ions.…”

“…87–89 Since Ag + ions have previously been reported to inhibit enzyme activity via interaction with cysteine residues, pepsin was incubated with AgNO 3 . 68, 69 Only minor reductions in activity were observed. Pepsin has two aspartic residues, Asp32 and Asp215, within the catalytic site, as well as 6 cysteine residues within the entire protein.…”

Interaction of firefly luciferase and silver nanoparticles and its impact on enzyme activity

“…Also, soil exoenzyme activities, especially for urease and dehydrogenases, were influenced by citrate-coated AgNPs [28]. AgNPs also hindered the activity of creatine kinase from rat brain and skeletal muscle in vitro, presumably through interactions with the thiol groups of the enzyme [29]. It should be pointed out that ligands and enzymes with thiol groups within mammalian cells like glutathione, thioredoxin, superoxide dismutase, and thioredoxin peroxidase are key components of the cell's antioxidant defense mechanism, which is responsible for neutralizing intracellular ROS largely generated by mitochondrial energy metabolism [30].…”