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1.
J Enzyme Inhib Med Chem ; 35(1): 129-137, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31694426

RESUMO

The 3-hydroxy-3-methylglutaryl-CoA reductase, a key enzyme of the mevalonate pathway for the synthesis of cholesterol in mammals (ergosterol in fungi), is inhibited by statins, a class of cholesterol lowering drugs. Indeed, statins are in a wide medical use, yet statins treatment could induce side effects as hepatotoxicity and myopathy in patients. We used Saccharomyces cerevisiae as a model to investigate the effects of statins on mitochondria. We demonstrate that statins are active in S.cerevisiae by lowering the ergosterol content in cells and interfering with the attachment of mitochondrial DNA to the inner mitochondrial membrane. Experiments on murine myoblasts confirmed these results in mammals. We propose that the instability of mitochondrial DNA is an early indirect target of statins.


Assuntos
DNA Mitocondrial/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/metabolismo , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Saccharomyces cerevisiae/química , DNA Mitocondrial/química , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Membranas Mitocondriais/química
2.
Food Chem ; 302: 125288, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31419774

RESUMO

The effects of benzothiadiazole (BTH) on Penicillium expansum development, mitochondria energy metabolism, and changes in the number and structure of mitochondria in apple fruit were investigated after the fruit were immersed in 100 mg L-1 BTH for 10 min and then stored at 22 °C. The results indicated that BTH treatment significantly decreased the lesion diameter of fruit challenged with P. expansum; further, treatment enhanced the activities of mitochondrial respiratory metabolism-related enzymes, such as succinate dehydrogenase, cytochrome oxidase, H+-ATPase and Ca2+-ATPase, along with high ATP level and energy status in apple fruit during storage. Moreover, transmission electron microscopy results indicated that BTH treatment was beneficial for maintaining the number and structure of mitochondria during storage. The results suggested that BTH treatment enhanced ATP levels via mitochondrial energy metabolism, which might contribute to the induced resistance in apple fruit during storage.


Assuntos
Metabolismo Energético/efeitos dos fármacos , Armazenamento de Alimentos , Frutas/metabolismo , Malus/efeitos dos fármacos , Malus/metabolismo , Mitocôndrias/efeitos dos fármacos , Tiadiazóis/farmacologia , Frutas/microbiologia , Malus/microbiologia , Mitocôndrias/metabolismo , Penicillium/fisiologia
3.
Adv Exp Med Biol ; 1131: 699-718, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646531

RESUMO

Calcium exchanges and homeostasis are finely regulated between cellular organelles and in response to physiological signals. Besides ionophores, including voltage-gated Ca2+ channels, ionotropic neurotransmitter receptors, or Store-operated Ca2+ entry, activity of regulatory intracellular proteins finely tune Calcium homeostasis. One of the most intriguing, by its unique nature but also most promising by the therapeutic opportunities it bears, is the sigma-1 receptor (Sig-1R). The Sig-1R is a chaperone protein residing at mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), where it interacts with several partners involved in ER stress response, or in Ca2+ exchange between the ER and mitochondria. Small molecules have been identified that specifically and selectively activate Sig-1R (Sig-1R agonists or positive modulators) at the cellular level and that also allow effective pharmacological actions in several pre-clinical models of pathologies. The present review will summarize the recent data on the mechanism of action of Sig-1R in regulating Ca2+ exchanges and protein interactions at MAMs and the ER. As MAMs alterations and ER stress now appear as a common track in most neurodegenerative diseases, the intracellular action of Sig-1R will be discussed in the context of the recently reported efficacy of Sig-1R drugs in pathologies like Alzheimer's disease, Parkinson's disease, Huntington's disease, or amyotrophic lateral sclerosis.


Assuntos
Membrana Celular , Estresse do Retículo Endoplasmático , Doenças Neurodegenerativas , Receptores sigma , Membrana Celular/metabolismo , Membrana Celular/patologia , Humanos , Mitocôndrias/metabolismo , Doenças Neurodegenerativas/fisiopatologia , Receptores sigma/metabolismo
4.
Adv Exp Med Biol ; 1131: 747-770, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646533

RESUMO

The pioneering work of Richard Altman on the presence of mitochondria in cells set in motion a field of research dedicated to uncovering the secrets of the mitochondria. Despite limitations in studying the structure and function of the mitochondria, advances in our understanding of this organelle prompted the development of potential treatments for various diseases, from neurodegenerative conditions to muscular dystrophy and cancer. As the powerhouses of the cell, the mitochondria represent the essence of cellular life and as such, a selective advantage for cancer cells. Much of the function of the mitochondria relies on Ca2+ homeostasis and the presence of effective Ca2+ signaling to maintain the balance between mitochondrial function and dysfunction and subsequently, cell survival. Ca2+ regulates the mitochondrial respiration rate which in turn increases ATP synthesis, but too much Ca2+ can also trigger the mitochondrial apoptosis pathway; however, cancer cells have evolved mechanisms to modulate mitochondrial Ca2+ influx and efflux in order to sustain their metabolic demand and ensure their survival. Therefore, targeting the mitochondrial Ca2+ signaling involved in the bioenergetic and apoptotic pathways could serve as potential approaches to treat cancer patients. This chapter will review the role of Ca2+ signaling in mediating the function of the mitochondria and its involvement in health and disease with special focus on the pathophysiology of cancer.


Assuntos
Sinalização do Cálcio , Cálcio , Mitocôndrias , Neoplasias , Apoptose , Cálcio/metabolismo , Sinalização do Cálcio/fisiologia , Homeostase , Humanos , Mitocôndrias/fisiologia , Neoplasias/fisiopatologia
5.
Adv Exp Med Biol ; 1131: 719-746, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646532

RESUMO

It is generally accepted that interorganellar contacts are central to the control of cellular physiology. Virtually, any intracellular organelle can come into proximity with each other and, by establishing physical protein-mediated contacts within a selected fraction of the membrane surface, novel specific functions are acquired. Endoplasmic reticulum (ER) contacts with mitochondria are among the best studied and have a major role in Ca2+ and lipid transfer, signaling, and membrane dynamics.Their functional (and structural) diversity, their dynamic nature as well as the growing number of new players involved in the tethering concurred to make their monitoring difficult especially in living cells. This review focuses on the most established examples of tethers/modulators of the ER-mitochondria interface and on the roles of these contacts in health and disease by specifically dissecting how Ca2+ transfer occurs and how mishandling eventually leads to disease. Additional functions of the ER-mitochondria interface and an overview of the currently available methods to measure/quantify the ER-mitochondria interface will also be discussed.


Assuntos
Cálcio , Retículo Endoplasmático , Mitocôndrias , Doenças Neurodegenerativas , Cálcio/metabolismo , Sinalização do Cálcio , Retículo Endoplasmático/metabolismo , Humanos , Mitocôndrias/metabolismo , Doenças Neurodegenerativas/fisiopatologia , Transdução de Sinais
6.
Biochemistry (Mosc) ; 84(10): 1143-1150, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31694510

RESUMO

Mitochondria are essential organelles of eukaryotic cell that provide its respiratory function by means of the electron transfer chain. Expression of mitochondrial genes is organized in a bacterial-like manner; however multiple evolutionary differences are observed between the two systems, including translation initiation machinery. This review is dedicated to the mitochondrial translation initiation factor 3 (IF3mt), which plays a key role in the protein synthesis in mitochondria. Involvement of IF3mt in human health and disease is discussed.


Assuntos
Fatores de Iniciação em Eucariotos/química , Fatores de Iniciação em Eucariotos/metabolismo , Proteínas Mitocondriais/química , Proteínas Mitocondriais/metabolismo , Doença de Parkinson/metabolismo , Humanos , Mitocôndrias/metabolismo
7.
Zootaxa ; 4638(1): zootaxa.4638.1.8, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31712489

RESUMO

Heliothrips longisensibilis sp. n. is described from the tropical regions of southern China, Yunnan and Hainan, based on morphology and data from mitochondrial and nuclear genes. However, specimens that are identical in colour and structure are reported from northern Brazil, and this is presumably the area of origin of this new species. The area of origin within South America of the Greenhouse Thrips, Heliothrips haemorrhoidalis, is discussed and remains in doubt. An identification key to the four species of Heliothrips is provided.


Assuntos
Tisanópteros , Animais , Brasil , Núcleo Celular , China , Mitocôndrias
8.
Zootaxa ; 4619(1): zootaxa.4619.1.6, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31716318

RESUMO

Species delimitation attempts to match species-level taxonomy with actual evolutionary lineages. Such taxonomic conclusions are typically, but not always, based on patterns of congruence across multiple data sources and methods of analyses. Here, we use this pluralistic approach to species delimitation to help resolve uncertainty in species boundaries of phrynosomatid sand lizards of the genus Holbrookia. Specifically, the Spot-tailed Earless Lizard (H. lacerata) was historically divided into a northern (H. l. lacerata) and southern (H. l. subcaudalis) subspecies based on differences in morphology and allopatry, but no research has been conducted evaluating genetic differences between these taxa. In this study, patterns in sequence data derived from two genes, one nuclear and one mitochondrial, for 66 individuals sampled across 18 counties in Texas revealed three strongly supported, reciprocally monophyletic lineages, each comprised of individuals from a single geographic region. Distinct genetic variation evident across two of these regions corresponds with differences in morphology, differences in environmental niche, and lines up with the presumed geographic barrier, the Balcones Escarpment, which is the historical subspecies boundary. The combined evidence from genetics, morphology and environmental niche is sufficient to consider these subspecies as distinct species with the lizards north of the Balcones Escarpment retaining the name Holbrookia lacerata, and those south of the Balcones Escarpment being designated as Holbrookia subcaudalis.


Assuntos
Lagartos , Animais , Evolução Biológica , DNA Mitocondrial , Mitocôndrias , Filogenia , Texas
9.
Zootaxa ; 4615(3): zootaxa.4615.3.1, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31716329

RESUMO

The Iberian species of the genera Coscinia Hübner, [1819] and Spiris Hübner, [1819], as well as three other species from the Mediterranean area, are revised based on morphological and molecular genetic data. Our results suggest the separation into four morphologically and phylogenetically different genera: Coscinia Hübner, [1819], Lerautia Kemal Koçak, 2006 stat. rev., Sagarriella Macià, Mally, Ylla, Gastón Huertas gen. nov. and Spiris Hübner, [1819]. We conclude that there are eight species of the Coscinia genus group present in the studied area: Coscinia cribraria (Linnaeus, 1758), Coscinia chrysocephala (Hübner, [1810]) stat. rev., Coscinia mariarosae Expósito, 1991, Sagarriella libyssa caligans (Turati, 1907) comb. nov., Sagarriella romei (Sagarra, 1924) (= romeii sensu auctorum) comb. nov., Spiris striata Hübner, [1819], Spiris slovenica (Daniel, 1939) and Lerautia bifasciata (Rambur, 1832) comb. rev. We consider Coscinia cribraria benderi (Marten, 1957) stat. nov., Coscinia c. rippertii (Boisduval, 1834) and Coscinia c. ibicenca Kobes, 1991 stat. rev. to be subspecies of C. cribraria. COI Barcodes of C. cribraria diverge by up to 7.99%, and the investigated specimens group into six different COI Barcode BINs. Both the phylogenetic analysis of mitochondrial and nuclear DNA and the morphological examination of different specimens corroborate the changes in taxonomic status and justify the proposed taxonomic categories. We present images of adults and genitalia of both sexes, the immature stages of some of the species and the subspecies studied, as well as phylogenetic results from the analysis of genetic data. We also include data on life history, foodplants and geographical distribution.


Assuntos
Mariposas , Mustelidae , Animais , Feminino , Genitália , Masculino , Mitocôndrias , Filogenia
10.
Zootaxa ; 4563(3): zootaxa.4563.3.8, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-31716534

RESUMO

The long-tailed parakeets of the genus Psittacula Cuvier, 1800 have thus far been regarded as a homogeneous and monophyletic group of parrots. We used nucleotide sequences of two genetic markers (mitochondrial CYTB, nuclear RAG-1) to reconstruct the phylogenetic relationships of Psittacula and closely related species. We found that the Asian genus Psittacula is apparently paraphyletic because two genera of short-tailed parrots, Psittinus Blyth, 1842 and Tanygnathus Wagler, 1832, cluster within Psittacula, as does †Mascarinus Lesson, 1830. To create monophyletic genera, we propose recognition of the following genera: Himalayapsitta Braun, 2016 for P. himalayana, P. finschii, P. roseata, and P. cyanocephala; Nicopsitta Braun, 2016 for P. columboides and P. calthrapae; Belocercus S. Müller, 1847 for P. longicauda; Psittacula Cuvier, 1800 for P. alexandri and P. derbiana; Palaeornis Vigors, 1825 for †P. wardi and P. eupatria; and Alexandrinus Braun, 2016 for P. krameri, †P. exsul, and P. (eques) echo. Additionally, Psittacula krameri and P. alexandri are paraphyletic species, which should be split to form monophyletic species.


Assuntos
Papagaios , Psittaciformes , Psittacula , Animais , Sequência de Bases , Mitocôndrias , Filogenia
11.
Zootaxa ; 4651(3): zootaxa.4651.3.1, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31716895

RESUMO

A lotic-breeding salamander Hynobius stejnegeri, formerly called H. yatsui, from western Japan is revised based on genetic and morphological evidence, and three species are described: H. guttatus sp. nov. from Chubu-Kinki districts of Honshu Island, H. tsurugiensis sp. nov. from east highland of Shikoku Island, and H. kuishiensis sp. nov. from other parts of Shikoku Island. Thus, H. stejnegeri sensu stricto is restricted to Kyushu Island. Of these four species, H. kuishiensis sp. nov. contains two distinct mitochondrial lineages, but this split is not reflected in differentiation of allozyme (nuclear genome) markers. These species are morphologically similar to each other but can be differentiated by several characteristics, especially in combination of dorsal coloration, the number of vomerine, upper, and lower jaw teeth, and depth of vomerine teeth series. In coloration, H. guttatus sp. nov. is brown or dark brown mostly with tiny white to brownish white marking, while H. tsurugiensis sp. nov. is dark brown with bright yellow continuous markings. Hynobius kuishiensis sp. nov. is reddish purple or dark brown with small to continuous brownish white markings, in contrast to reddish purple or dark brown with small to large brownish white markings in H. stejnegeri.


Assuntos
Urodelos , Animais , Cruzamento , Japão , Mitocôndrias , Filogenia , Dente
12.
Zootaxa ; 4571(1): zootaxa.4571.1.6, 2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-31715832

RESUMO

Neochloroglyphica gen. nov. and its type species N. perbella sp. nov. are described from Yunnan, China. Morphological characters and molecular phylogenetic analysis, based on one mitochondrial and three nuclear genes, support the hypothesis that Neochloroglyphica is a member of the tribe Neohipparchini, and that it is a sister genus to Chloroglyphica. Morphological characters, including those of the genitalia, are figured and compared with related genera, especially Chloroglyphica, Neohipparchus and Chlororithra. Diagnoses for the genus and the species are provided and illustrations of external features and genitalia are presented.


Assuntos
Lepidópteros , Mariposas , Animais , China , Genitália , Mitocôndrias , Filogenia
13.
Biochemistry (Mosc) ; 84(11): 1247-1255, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31760915

RESUMO

Fo×F1-ATPases of mitochondria, chloroplasts, and microorganisms catalyze transformation of proton motive force (the difference between the electrochemical potentials of hydrogen ion across a coupling membrane) to the free energy of ATP phosphoryl potential. It is often stated that Fo×F1-ATPases operate as reversible chemo-mechano-electrical molecular machines that provide either ATP synthesis or hydrolysis depending on particular physiological demands of an organism; the microreversibility principle of the enzyme catalysis is usually taken as a dogma. Since 1980, the author has upheld the view that the mechanisms of ATP synthesis and hydrolysis by the Fo×F1 complex are different (Vinogradov, A. D. (2000) J. Exp. Biol., 203, 41-49). In this paper, the author proposes a new model considering the existence in coupling membranes of two non-equilibrium isoforms of Fo×F1 unidirectionally catalyzing synthesis and/or hydrolysis of ATP.


Assuntos
Trifosfato de Adenosina/metabolismo , ATPases Translocadoras de Prótons/metabolismo , Biocatálise , Cloroplastos/enzimologia , Hidrólise , Cinética , Mitocôndrias/enzimologia , Paracoccus denitrificans/enzimologia , Força Próton-Motriz
14.
Biochemistry (Mosc) ; 84(11): 1359-1374, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31760923

RESUMO

The review summarizes the data of our research and published studies on the ubiquitination of brain mitochondrial proteins and its changes during the development of experimental parkinsonism and administration of the neuroprotector isatin (indole-2,3-dione) with special attention to the mitochondrial ubiquitin-conjugating system and location of ubiquitinated proteins in these organelles. Incubation of brain mitochondrial fraction with biotinylated ubiquitin in vitro resulted in the incorporation of biotinylated ubiquitin in both mitochondrial and mitochondria-associated proteins. According to the interactome analysis, the identified non-ubiquitinated proteins are able to form tight complexes with ubiquitinated proteins or their partners and components of mitochondrial membranes, in which interactions of ubiquitin chains with the ubiquitin-binding protein domains play an important role. The studies of endogenous ubiquitination in the total brain mitochondrial fraction of C57Bl mice performed in different laboratories have shown that mitochondrial proteins represent about 30% of all ubiquitinated proteins. However, comparison of brain subproteomes of mitochondrial ubiquitinated proteins reported in the literature revealed significant differences both in their composition and involvement of identified ubiquitinated proteins in biological processes listed in the Gene Ontology database. The development of experimental parkinsonism in C57Bl mice induced by a single-dose administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) resulted in a decrease in the total number of mitochondrial ubiquitinated proteins and increase in the number of oxidized mitochondrial proteins containing the ubiquitin signature (K-ε-GG). Comparison of ubiquitinated proteins associated with the mouse brain mitochondrial fraction and mouse brain mitochondrial proteins bound to the proteasome ubiquitin receptor (Rpn10 subunit) did not reveal any common proteins. This suggests that ubiquitination of brain mitochondrial proteins is not directly related to their degradation in the proteasomes. Proteomic profiling of brain isatin-binding proteins identified enzymes involved in the ubiquitin-conjugating system functioning. Mapping of the identified isatin-binding proteins to known metabolic pathways indicates their participation in the parkin (E3 ubiquitin ligase)-associated pathway (CH000000947). The functional links involving brain mitochondrial ubiquitinated proteins were found only in the group of animals with the MPTP-induced parkinsonism, but not in animals treated with MPTP/isatin or isatin only. This suggests that the neuroprotective effect of isatin may be associated with the impaired functional relationships of proteins targeted to subsequent degradation.


Assuntos
Encéfalo/metabolismo , Transtornos Parkinsonianos/patologia , Ubiquitina/metabolismo , Animais , Autofagia , Redes e Vias Metabólicas , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/veterinária , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitinação
15.
Biochemistry (Mosc) ; 84(11): 1411-1423, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31760927

RESUMO

Ischemic stroke and neonatal hypoxic-ischemic encephalopathy are two of the leading causes of disability in adults and infants. The energy demands of the brain are provided by mitochondrial oxidative phosphorylation. Ischemia/reperfusion (I/R) affects the production of ATP in brain mitochondria, leading to energy failure and death of the affected tissue. Among the enzymes of the mitochondrial respiratory chain, mitochondrial complex I is the most sensitive to I/R; however, the mechanisms of its inhibition are poorly understood. This article reviews some of the existing data on the mitochondria impairment during I/R and proposes two distinct mechanisms of complex I damage emerging from recent studies. One mechanism is a reversible dissociation of natural flavin mononucleotide cofactor from the enzyme I after ischemia. Another mechanism is a modification of critical cysteine residue of complex I involved into the active/deactive conformational transition of the enzyme. I describe potential effects of these two processes in the development of mitochondrial I/R injury and briefly discuss possible neuroprotective strategies to ameliorate I/R brain injury.


Assuntos
Encéfalo/metabolismo , Complexo I de Transporte de Elétrons/metabolismo , Traumatismo por Reperfusão/patologia , Animais , Flavinas/química , Flavinas/metabolismo , Humanos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Compostos de Sulfidrila/química
16.
J Biomed Nanotechnol ; 15(12): 2428-2438, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31748022

RESUMO

Limited understanding of mitochondria disorders that induced by nanoparticles is a stumbling block for anti-cancer drug delivery targeting strategy. In present study, C6 glioma cells were exposed to aminated and alkylated SiO2 nanoparticles for mitochondrion disordering and cell metabolism study. Collective results showed that aminated nanoparticles tend to trigger the cell-repair mechanism in cancer cells while alkylated nanoparticles could cause irreversible damages on cancer cells, although both types of the particles were proved to damage mitochondrion. The underlying mechanism show that aminated nanoparticles induced proton-stuck effect in mitochondrion and self-repairing in cancer cells by up-regulating p21. Otherwise, alkylated nanoparticles damaged mitochondrion and induced phosphorylated cyclin E accumulation lead to Fbw7 down-regulation caused further S phase arrest and severe late apoptosis. This work can help us elucidate the mechanism of the clinic application of nano-drug carriers.


Assuntos
Nanopartículas , Apoptose , Cátions , Linhagem Celular Tumoral , Humanos , Mitocôndrias , Dióxido de Silício
17.
Bratisl Lek Listy ; 120(7): 516-522, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31602987

RESUMO

OBJECTIVES: The aim of this study was to evaluate the toxic effect of AlNPs on rat brain mitochondria and compare it with that of aluminium's ionic form. METHODS: Mitochondria were isolated from rat brain. Isolated mitochondria were treated with normal saline (Control) and different concentrations of aluminium ions (AlIs) and AlNPs (50, 100 and 200 µM). Then, the effect of AlNPs on electron transport chain complexes as well as various endpoints such as mitochondrial oxidative damage (reactive oxygen species, lipid peroxidation, glutathione, and protein carbonyl) and mitochondrial function were assessed. Also, apoptosis was evaluated by cytochrome c release, mitochondrial membrane potential and swelling. RESULTS: When compared to the control group, the exposure to AlNPs showed a marked elevation in oxidative stress markers and inhibition of complex III which was accompanied by disturbance in mitochondrial function. Also, AlNPs induced a significant collapse of mitochondrial membrane potential, mitochondrial swelling, and cytochrome c release. CONCLUSIONS: The comparison of mitochondrial toxicity markers between both forms of aluminium revealed that the toxic effect of AlNPs on isolated brain mitochondria was substantially greater than that that caused by AlIs, which can probably be ascribed to its higher reactivity (Tab. 1, Fig. 8, Ref. 45).


Assuntos
Alumínio/toxicidade , Encéfalo/diagnóstico por imagem , Mitocôndrias/efeitos dos fármacos , Nanopartículas/toxicidade , Animais , Apoptose , Citocromos c/metabolismo , Glutationa/metabolismo , Íons , Peroxidação de Lipídeos , Potencial da Membrana Mitocondrial , Estresse Oxidativo , Carbonilação Proteica , Ratos , Espécies Reativas de Oxigênio/metabolismo
18.
Yi Chuan ; 41(10): 893-904, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31624052

RESUMO

Mitochondrion is the metabolic center and powerhouse of cells producing cellular energy which plays an important role in various physiological and pathophysiological processes. Recent research demonstrates that mitochondrial energy metabolism mediates the transmission of mitochondrial-nuclear signals through intermediate products which regulates epigenetic presentation of the chromatin and thereby affects gene expression. Epigenetic modification, a genetic regulatory model, is independent of DNA sequence and plays a major role in establishing and maintaining a specific gene's expression profile. Disorders of mitochondrial metabolism can induce epigenetic reprogramming which in turn initiates aging phenotypes and degenerative diseases. This review introduces recent research progress on the relationship between mitochondrial metabolism and chromatin-related epigenetic modification, discusses the role of mitochondrial stress in chromatin recombination, and suggests future research directions and their application in the study of age-related diseases such as cognitive dysfunction.


Assuntos
Envelhecimento , Cromatina , Epigênese Genética , Mitocôndrias/metabolismo , Humanos
19.
Sheng Li Xue Bao ; 71(5): 792-798, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31646333

RESUMO

Aberrant oxidative metabolism in cells is one of the hallmarks of cancer. Overproduction of reactive species promotes carcinogenesis by inducing genetic mutations and activating oncogenic pathways, and thus, antioxidant therapy is considered as an important strategy for cancer prevention and treatment. Caveolin-1 (Cav-1), a constituent protein of caveolae, is involved in not only the formation of the caveolae, vesicular transport, maintaining cholesterol homeostasis directly, but also many cellular physiological and pathological processes including growth, regulation of mitochondrial antioxidant level, apoptosis and carcinomas by interacting with a lot of signaling molecules through caveolin scaffolding domain. Cav-1 has also been shown to mediate tumor genesis and progression through oxidative stress modulation, while Cav-1-targeted treatment could scavenge the reactive species. Intracellular reactive species could modulate the expression, degradation, post-translational modifications and membrane trafficking of Cav-1. More importantly, emerging evidence has indicated that multiple antioxidants could exert antitumor activities in cancer cells by modulating the signaling of Cav-1. This paper reviewed the research progresses on the roles of Cav-1 and oxidative stress in tumorigenesis and development, and would provide new insights on designing strategies for cancer prevention or treatment.


Assuntos
Caveolina 1 , Neoplasias/patologia , Estresse Oxidativo , Antioxidantes , Apoptose , Carcinogênese , Carcinoma/patologia , Humanos , Mitocôndrias , Transdução de Sinais
20.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(9): 1030-1037, 2019 Sep 30.
Artigo em Chinês | MEDLINE | ID: mdl-31640957

RESUMO

OBJECTIVE: To investigate the relationship between necroptosis and apoptosis in MCET3-E1 cell death induced by glucocorticoids. METHODS: MC3T3-E1 cells were incubated with 10-6 mol/L dexamethasone followed by treatment with the apoptosis inhibitor z-VAD-fmk (40 µmol/L) or the necroptosis inhibitor necrostatin-1 (40 µmol/L) for 2 h. At 72 h after incubation with dexamethasone, the cells were harvested to determine the cell viability using WST-1 assay and the rate of necrotic cells using annexin V/PI double staining; the percentage of apoptotic cells was determined using Hoechst staining. The mitochondrial membrane potential and the level of ATP in the cells were also evaluated. Transmission electron microscopy was used to observe the microstructural changes of the cells. The expressions of RIP-1 and RIP-3 in the cells were detected by Western blotting. RESULTS: At a concentration of 10-6 mol/L, dexamethasone induced both apoptosis and necroptosis in MC3T3- E1 cells. Annexin V/PI double staining showed that inhibition of cell apoptosis caused an increase in cell necrosis manifested by such changes as mitochondrial swelling and plasma membrane disruption, as shown by electron microscopy; Hoechst staining showed that the percentage of apoptotic cells was significantly reduced. When necroptosis was inhibited by necrostatin-1, MC3T3-E1 cells showed significantly increased apoptosis as shown by both AV/PI and Hoechst staining, and such changes were accompanied by changes in mitochondrial membrane potential and ATP level in the cells. CONCLUSIONS: In the process of dexamethasone-induced cell death, necroptosis and apoptosis can transform reciprocally accompanied by functional changes of the mitochondria.


Assuntos
Apoptose , Morte Celular/efeitos dos fármacos , Dexametasona , Necrose , Células 3T3 , Trifosfato de Adenosina , Animais , Potencial da Membrana Mitocondrial , Camundongos , Microscopia Eletrônica , Mitocôndrias/ultraestrutura
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