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1.
Cell ; 151(7): 1406-16, 2012 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-23260134

RESUMO

Harnessing energy as ion gradients across membranes is as universal as the genetic code. We leverage new insights into anaerobe metabolism to propose geochemical origins that account for the ubiquity of chemiosmotic coupling, and Na(+)/H(+) transporters in particular. Natural proton gradients acting across thin FeS walls within alkaline hydrothermal vents could drive carbon assimilation, leading to the emergence of protocells within vent pores. Protocell membranes that were initially leaky would eventually become less permeable, forcing cells dependent on natural H(+) gradients to pump Na(+) ions. Our hypothesis accounts for the Na(+)/H(+) promiscuity of bioenergetic proteins, as well as the deep divergence between bacteria and archaea.


Assuntos
Archaea/metabolismo , Bactérias/metabolismo , Metabolismo Energético , Fontes Hidrotermais/microbiologia , Bombas de Íon/metabolismo , Proteínas Arqueais/química , Proteínas Arqueais/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Membrana Celular/química , Membrana Celular/metabolismo , Bombas de Íon/química , Osmose , Força Próton-Motriz
2.
J Am Chem Soc ; 145(20): 10938-10942, 2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-37083435

RESUMO

Microbial rhodopsins are a large family of photoreceptive membrane proteins with diverse light-regulated functions. While the most ubiquitous microbial rhodopsins are light-driven outward proton (H+) pumps, new subfamilies of microbial rhodopsins transporting H+ inwardly, i.e., light-driven inward H+ pumps, have been discovered recently. Although structural and spectroscopic studies provide insights into their ion transport mechanisms, the minimum key element(s) that determine the direction of H+ transport have not yet been clarified. Here, we conducted the first functional conversion study by substituting key amino acids in a natural outward H+-pumping rhodopsin (PspR) with those in inward H+-pumping rhodopsins. Consequently, an artificial inward H+ pump was constructed by mutating only three residues of PspR. This result indicates that these residues govern the key processes that discriminate between outward and inward H+ pumps. Spectroscopic studies revealed the presence of an inward H+-accepting residue in the H+ transport pathway and direct H+ uptake from the extracellular solvent. This finding of the simple element for determining H+ transport would provide a new basis for understanding the concept of ion transport not only by microbial rhodopsins but also by other ion-pumping proteins.


Assuntos
Bombas de Próton , Rodopsina , Bombas de Próton/química , Rodopsina/química , Rodopsinas Microbianas/metabolismo , Transporte de Íons , Bombas de Íon/metabolismo , Prótons , Luz
3.
Plant Physiol ; 187(4): 1856-1875, 2021 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-35235671

RESUMO

Plant plasma membrane H+-ATPases and Ca2+-ATPases maintain low cytoplasmic concentrations of H+ and Ca2+, respectively, and are essential for plant growth and development. These low concentrations allow plasma membrane H+-ATPases to function as electrogenic voltage stats, and Ca2+-ATPases as "off" mechanisms in Ca2+-based signal transduction. Although these pumps are autoregulated by cytoplasmic concentrations of H+ and Ca2+, respectively, they are also subject to exquisite regulation in response to biotic and abiotic events in the environment. A common paradigm for both types of pumps is the presence of terminal regulatory (R) domains that function as autoinhibitors that can be neutralized by multiple means, including phosphorylation. A picture is emerging in which some of the phosphosites in these R domains appear to be highly, nearly constantly phosphorylated, whereas others seem to be subject to dynamic phosphorylation. Thus, some sites might function as major switches, whereas others might simply reduce activity. Here, we provide an overview of the relevant transport systems and discuss recent advances that address their relation to external stimuli and physiological adaptations.


Assuntos
Adaptação Fisiológica/efeitos dos fármacos , ATPases Transportadoras de Cálcio/metabolismo , Cálcio/metabolismo , Bombas de Íon/metabolismo , Fenômenos Fisiológicos Vegetais/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , ATPases Translocadoras de Prótons/metabolismo , Transdução de Sinais/efeitos dos fármacos , Membrana Celular/metabolismo
4.
Physiol Plant ; 174(3): e13702, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35524987

RESUMO

Soil salinity is one of the most serious threats to plant growth and productivity. Due to global climate change, burgeoning population and shrinking arable land, there is an urgent need to develop crops with minimum reduction in yield when cultivated in salt-affected areas. Salinity stress imposes osmotic stress as well as ion toxicity, which impairs major plant processes such as photosynthesis, cellular metabolism, and plant nutrition. One of the major effects of salinity stress in plants includes the disturbance of ion homeostasis in various tissues. In the present study, we aimed to review the regulation of uptake, transport, storage, efflux, influx, and accumulation of various ions in plants under salinity stress. We have summarized major research advancements towards understanding the ion homeostasis at both cellular and whole-plant level under salinity stress. We have also discussed various factors regulating the function of ion transporters and channels in maintaining ion homeostasis and ionic interactions under salt stress, including plant antioxidative defense, osmo-protection, and osmoregulation. We further elaborated on stress perception at extracellular and intracellular levels, which triggers downstream intracellular-signaling cascade, including secondary messenger molecules generation. Various signaling and signal transduction mechanisms under salinity stress and their role in improving ion homeostasis in plants are also discussed. Taken together, the present review focuses on recent advancements in understanding the regulation and function of different ion channels and transporters under salt stress, which may pave the way for crop improvement.


Assuntos
Bombas de Íon/metabolismo , Salinidade , Tolerância ao Sal , Íons , Plantas/metabolismo , Transdução de Sinais , Estresse Fisiológico
5.
Int J Mol Sci ; 23(3)2022 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-35163766

RESUMO

Bipolar disorder (BD) is a severe psychiatric illness with a poor prognosis and problematic, suboptimal, treatments. Treatments, borne of an understanding of the pathoetiologic mechanisms, need to be developed in order to improve outcomes. Dysregulation of cationic homeostasis is the most reproducible aspect of BD pathophysiology. Correction of ionic balance is the universal mechanism of action of all mood stabilizing medications. Endogenous sodium pump modulators (collectively known as endogenous cardiac steroids, ECS) are steroids which are synthesized in and released from the adrenal gland and brain. These compounds, by activating or inhibiting Na+, K+-ATPase activity and activating intracellular signaling cascades, have numerous effects on cell survival, vascular tone homeostasis, inflammation, and neuronal activity. For the past twenty years we have addressed the hypothesis that the Na+, K+-ATPase-ECS system may be involved in the etiology of BD. This is a focused review that presents a comprehensive model pertaining to the role of ECS in the etiology of BD. We propose that alterations in ECS metabolism in the brain cause numerous biochemical changes that underlie brain dysfunction and mood symptoms. This is based on both animal models and translational human results. There are data that demonstrate that excess ECS induce abnormal mood and activity in animals, while a specific removal of ECS with antibodies normalizes mood. There are also data indicating that circulating levels of ECS are lower in manic individuals, and that patients with BD are unable to upregulate synthesis of ECS under conditions that increase their elaboration in non-psychiatric controls. There is strong evidence for the involvement of ion dysregulation and ECS function in bipolar illness. Additional research is required to fully characterize these abnormalities and define future clinical directions.


Assuntos
Transtorno Bipolar/metabolismo , Bombas de Íon/metabolismo , Esteroides/sangue , Animais , Transtorno Bipolar/psicologia , Encéfalo/metabolismo , Regulação para Baixo , Humanos , Transdução de Sinais , Esteroides/metabolismo
6.
Traffic ; 20(5): 311-324, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30972921

RESUMO

Get3 in yeast or TRC40 in mammals is an ATPase that, in eukaryotes, is a central element of the GET or TRC pathway involved in the targeting of tail-anchored proteins. Get3 has also been shown to possess chaperone holdase activity. A bioinformatic assessment was performed across all domains of life on functionally important regions of Get3 including the TRC40-insert and the hydrophobic groove essential for tail-anchored protein binding. We find that such a hydrophobic groove is much more common in bacterial Get3 homologs than previously appreciated based on a directed comparison of bacterial ArsA and yeast Get3. Furthermore, our analysis shows that the region containing the TRC40-insert varies in length and methionine content to an unexpected extent within eukaryotes and also between different phylogenetic groups. In fact, since the TRC40-insert is present in all domains of life, we suggest that its presence does not automatically predict a tail-anchored protein targeting function. This opens up a new perspective on the function of organellar Get3 homologs in plants which feature the TRC40-insert but have not been demonstrated to function in tail-anchored protein targeting. Our analysis also highlights a large diversity of the ways Get3 homologs dimerize. Thus, based on the structural features of Get3 homologs, these proteins may have an unexplored functional diversity in all domains of life.


Assuntos
Adenosina Trifosfatases/química , ATPases Transportadoras de Arsenito/química , Evolução Molecular , Fatores de Troca do Nucleotídeo Guanina/química , Chaperonas Moleculares/química , Proteínas de Saccharomyces cerevisiae/química , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Animais , ATPases Transportadoras de Arsenito/genética , ATPases Transportadoras de Arsenito/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Humanos , Bombas de Íon/química , Bombas de Íon/genética , Bombas de Íon/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Complexos Multienzimáticos/química , Complexos Multienzimáticos/genética , Complexos Multienzimáticos/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Homologia de Sequência de Aminoácidos
7.
J Cell Physiol ; 236(10): 7117-7133, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33634482

RESUMO

The period beginning with the signal for ovulation, when a fully-grown oocyte progresses through meiosis to become a mature egg that is fertilized and develops as a preimplantation embryo, is crucial for healthy development. The early preimplantation embryo is unusually sensitive to cell volume perturbations, with even moderate decreases in volume or dysregulation of volume-regulatory mechanisms resulting in developmental arrest. To prevent this, early embryos possess mechanisms of cell volume control that are apparently unique to them. These rely on the accumulation of glycine and betaine (N, N, N-trimethylglycine) as organic osmolytes-compounds that can provide intracellular osmotic support without the deleterious effects of inorganic ions. Preimplantation embryos also have the same mechanisms as somatic cells that mediate rapid responses to deviations in cell volume, which rely on inorganic ion transport. Both the unique, embryo-specific mechanisms that use glycine and betaine and the inorganic ion-dependent mechanisms undergo major changes during meiotic maturation and preimplantation development. The most profound changes occur immediately after ovulation is triggered. Before this, oocytes cannot regulate their volume, since they are strongly attached to their rigid extracellular matrix shell, the zona pellucida. After ovulation is triggered, the oocyte detaches from the zona pellucida and first becomes capable of independent volume regulation. A complex set of developmental changes in each cell volume-regulatory mechanism continues through egg maturation and preimplantation development. The unique cell volume-regulatory mechanisms in eggs and preimplantation embryos and the developmental changes they undergo appear critical for normal healthy embryo development.


Assuntos
Betaína/metabolismo , Blastocisto/metabolismo , Tamanho Celular , Glicina/metabolismo , Bombas de Íon/metabolismo , Oócitos/metabolismo , Osmorregulação , Animais , Desenvolvimento Embrionário , Humanos , Pressão Osmótica , Ovulação
8.
Nat Rev Mol Cell Biol ; 10(5): 344-52, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19339978

RESUMO

The incessant traffic of ions across cell membranes is controlled by two kinds of border guards: ion channels and ion pumps. Open channels let selected ions diffuse rapidly down electrical and concentration gradients, whereas ion pumps labour tirelessly to maintain the gradients by consuming energy to slowly move ions thermodynamically uphill. Because of the diametrically opposed tasks and the divergent speeds of channels and pumps, they have traditionally been viewed as completely different entities, as alike as chalk and cheese. But new structural and mechanistic information about both of these classes of molecular machines challenges this comfortable separation and forces its re-evaluation.


Assuntos
Canais Iônicos/fisiologia , Bombas de Íon/fisiologia , Animais , Humanos , Canais Iônicos/química , Canais Iônicos/metabolismo , Bombas de Íon/química , Bombas de Íon/metabolismo , Estrutura Secundária de Proteína
9.
Nature ; 521(7550): 48-53, 2015 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-25849775

RESUMO

Krokinobacter eikastus rhodopsin 2 (KR2) is the first light-driven Na(+) pump discovered, and is viewed as a potential next-generation optogenetics tool. Since the positively charged Schiff base proton, located within the ion-conducting pathway of all light-driven ion pumps, was thought to prohibit the transport of a non-proton cation, the discovery of KR2 raised the question of how it achieves Na(+) transport. Here we present crystal structures of KR2 under neutral and acidic conditions, which represent the resting and M-like intermediate states, respectively. Structural and spectroscopic analyses revealed the gating mechanism, whereby the flipping of Asp116 sequesters the Schiff base proton from the conducting pathway to facilitate Na(+) transport. Together with the structure-based engineering of the first light-driven K(+) pumps, electrophysiological assays in mammalian neurons and behavioural assays in a nematode, our studies reveal the molecular basis for light-driven non-proton cation pumps and thus provide a framework that may advance the development of next-generation optogenetics.


Assuntos
Flavobacteriaceae/química , Bombas de Íon/química , Bombas de Íon/efeitos da radiação , Luz , Rodopsina/química , Rodopsina/efeitos da radiação , Sódio/metabolismo , Sítios de Ligação , Cristalografia por Raios X , Concentração de Íons de Hidrogênio , Bombas de Íon/genética , Bombas de Íon/metabolismo , Transporte de Íons/genética , Transporte de Íons/efeitos da radiação , Modelos Biológicos , Modelos Moleculares , Mutagênese/genética , Optogenética , Potássio/metabolismo , Conformação Proteica , Engenharia de Proteínas , Retinaldeído/química , Retinaldeído/metabolismo , Rodopsina/genética , Rodopsina/metabolismo , Bases de Schiff , Relação Estrutura-Atividade
10.
Adv Exp Med Biol ; 1293: 89-126, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33398809

RESUMO

Ion-transporting microbial rhodopsins are widely used as major molecular tools in optogenetics. They are categorized into light-gated ion channels and light-driven ion pumps. While the former passively transport various types of cations and anions in a light-dependent manner, light-driven ion pumps actively transport specific ions, such as H+, Na+, Cl-, against electrophysiological potential by using light energy. Since the ion transport by these pumps induces hyperpolarization of membrane potential and inhibit neural firing, light-driven ion-pumping rhodopsins are mostly applied as inhibitory optogenetics tools. Recent progress in genome and metagenome sequencing identified more than several thousands of ion-pumping rhodopsins from a wide variety of microbes, and functional characterization studies has been revealing many new types of light-driven ion pumps one after another. Since light-gated channels were reviewed in other chapters in this book, here the rapid progress in functional characterization, molecular mechanism study, and optogenetic application of ion-pumping rhodopsins were reviewed.


Assuntos
Bombas de Íon/metabolismo , Bombas de Íon/efeitos da radiação , Luz , Optogenética/métodos , Rodopsinas Microbianas/metabolismo , Rodopsinas Microbianas/efeitos da radiação , Bombas de Íon/genética , Transporte de Íons/efeitos da radiação , Rodopsinas Microbianas/genética
11.
Int J Mol Sci ; 22(24)2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34948045

RESUMO

Salt stress is one of the major significant restrictions that hamper plant development and agriculture ecosystems worldwide. Novel climate-adapted cultivars and stress tolerance-enhancing molecules are increasingly appreciated to mitigate the detrimental impacts of adverse stressful conditions. Sorghum is a valuable source of food and a potential model for exploring and understanding salt stress dynamics in cereals and for gaining a better understanding of their physiological pathways. Herein, we evaluate the antioxidant scavengers, photosynthetic regulation, and molecular mechanism of ion exclusion transporters in sorghum genotypes under saline conditions. A pot experiment was conducted in two sorghum genotypes viz. SSG 59-3 and PC-5 in a climate-controlled greenhouse under different salt concentrations (60, 80, 100, and 120 mM NaCl). Salinity drastically affected the photosynthetic machinery by reducing the accumulation of chlorophyll pigments and carotenoids. SSG 59-3 alleviated the adverse effects of salinity by suppressing oxidative stress (H2O2) and stimulating enzymatic and non-enzymatic antioxidant activities (SOD, APX, CAT, POD, GR, GST, DHAR, MDHAR, GSH, ASC, proline, GB), as well as protecting cell membrane integrity (MDA, electrolyte leakage). Salinity also influenced Na+ ion efflux and maintained a lower cytosolic Na+/K+ ratio via the concomitant upregulation of SbSOS1, SbSOS2, and SbNHX-2 and SbV-Ppase-II ion transporter genes in sorghum genotypes. Overall, these results suggest that Na+ ions were retained and detoxified, and less stress impact was observed in mature and younger leaves. Based on the above, we deciphered that SSG 59-3 performed better by retaining higher plant water status, photosynthetic assimilates and antioxidant potential, and the upregulation of ion transporter genes and may be utilized in the development of resistant sorghum lines in saline regions.


Assuntos
Ácido Ascórbico/metabolismo , Glutationa/metabolismo , Bombas de Íon/metabolismo , Metabolômica/métodos , Sorghum/crescimento & desenvolvimento , Antioxidantes/metabolismo , Carotenoides/metabolismo , Clorofila/metabolismo , Regulação da Expressão Gênica de Plantas , Genótipo , Fotossíntese , Proteínas de Plantas/metabolismo , Estresse Salino , Sorghum/genética , Sorghum/metabolismo , Regulação para Cima
12.
Int J Mol Sci ; 22(6)2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33804674

RESUMO

Intra- and extracellular pH regulation is a pivotal function of all cells and tissues. Net outward transport of H+ is a prerequisite for normal physiological function, since a number of intracellular processes, such as metabolism and energy supply, produce acid. In tumor tissues, distorted pH regulation results in extracellular acidification and the formation of a hostile environment in which cancer cells can outcompete healthy local host cells. Cancer cells employ a variety of H+/HCO3--coupled transporters in combination with intra- and extracellular carbonic anhydrase (CA) isoforms, to alter intra- and extracellular pH to values that promote tumor progression. Many of the transporters could closely associate to CAs, to form a protein complex coined "transport metabolon". While transport metabolons built with HCO3--coupled transporters require CA catalytic activity, transport metabolons with monocarboxylate transporters (MCTs) operate independently from CA catalytic function. In this article, we assess some of the processes and functions of CAs for tumor pH regulation and discuss the role of intra- and extracellular pH regulation for cancer pathogenesis and therapeutic intervention.


Assuntos
Anidrases Carbônicas/metabolismo , Neoplasias/metabolismo , Prótons , Animais , Biomarcadores , Anidrases Carbônicas/genética , Suscetibilidade a Doenças , Descoberta de Drogas , Metabolismo Energético/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Espaço Intracelular/metabolismo , Bombas de Íon/genética , Bombas de Íon/metabolismo , Transporte de Íons/efeitos dos fármacos , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/etiologia , Neoplasias/patologia
13.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072552

RESUMO

Indirect evidence has determined the possibility that microplastics (MP) induce constipation, although direct scientific proof for constipation induction in animals remains unclear. To investigate whether oral administration of polystyrene (PS)-MP causes constipation, an alteration in the constipation parameters and mechanisms was analyzed in ICR mice, treated with 0.5 µm PS-MP for 2 weeks. Significant alterations in water consumption, stool weight, stool water contents, and stool morphology were detected in MP treated ICR mice, as compared to Vehicle treated group. Also, the gastrointestinal (GI) motility and intestinal length were decreased, while the histopathological structure and cytological structure of the mid colon were remarkably altered in treated mice. Mice exposed to MP also showed a significant decrease in the GI hormone concentration, muscarinic acetylcholine receptors (mAChRs) expression, and their downstream signaling pathway. Subsequent to MP treatment, concentrations of chloride ion and expressions of its channel (CFTR and CIC-2) were decreased, whereas expressions of aquaporin (AQP)3 and 8 for water transportation were downregulated by activation of the mitogen-activated protein kinase (MAPK)/nuclear factor (NF)-κB signaling pathway. These results are the first to suggest that oral administration of PS-MP induces chronic constipation through the dysregulation of GI motility, mucin secretion, and chloride ion and water transportation in the mid colon.


Assuntos
Constipação Intestinal/diagnóstico , Constipação Intestinal/etiologia , Microplásticos/efeitos adversos , Fenótipo , Poliestirenos/efeitos adversos , Animais , Comportamento Animal , Biomarcadores , Fenômenos Químicos , Cloretos/metabolismo , Colo/patologia , Colo/ultraestrutura , Modelos Animais de Doenças , Suscetibilidade a Doenças , Hormônios Gastrointestinais/metabolismo , Motilidade Gastrointestinal , Bombas de Íon/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Microplásticos/química , Mucinas/metabolismo , Poliestirenos/química , Transdução de Sinais , Água/metabolismo
14.
Chem Rev ; 118(21): 10710-10747, 2018 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-29985590

RESUMO

Synthetic photoswitches have been known for many years, but their usefulness in biology, pharmacology, and medicine has only recently been systematically explored. Over the past decade photopharmacology has grown into a vibrant field. As the photophysical, pharmacodynamic, and pharmacokinetic properties of photoswitches, such as azobenzenes, have become established, they have been applied to a wide range of biological targets. These include transmembrane proteins (ion channels, transporters, G protein-coupled receptors, receptor-linked enzymes), soluble proteins (kinases, proteases, factors involved in epigenetic regulation), lipid membranes, and nucleic acids. In this review, we provide an overview of photopharmacology using synthetic switches that have been applied in vivo, i.e., in living cells and organisms. We discuss the scope and limitations of this approach to study biological function and the challenges it faces in translational medicine. The relationships between synthetic photoswitches, natural chromophores used in optogenetics, and caged ligands are addressed.


Assuntos
Compostos Azo/química , Derivados de Benzeno/química , Farmacologia , Processos Fotoquímicos , Animais , Transporte Biológico Ativo , Reagentes de Ligações Cruzadas/química , Citoesqueleto/metabolismo , Enzimas/metabolismo , Humanos , Canais Iônicos/metabolismo , Bombas de Íon/metabolismo , Ligantes , Luz , Optogenética , Biossíntese de Proteínas/efeitos da radiação
15.
Cell Mol Life Sci ; 76(19): 3783-3800, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31165202

RESUMO

In the male reproductive tract, ionic equilibrium is essential to maintain normal spermatozoa production and, hence, the reproductive potential. Among the several ions, HCO3- and H+ have a central role, mainly due to their role on pH homeostasis. In the male reproductive tract, the major players in pH regulation and homeodynamics are carbonic anhydrases (CAs), HCO3- membrane transporters (solute carrier 4-SLC4 and solute carrier 26-SLC26 family transporters), Na+-H+ exchangers (NHEs), monocarboxylate transporters (MCTs) and voltage-gated proton channels (Hv1). CAs and these membrane transporters are widely distributed throughout the male reproductive tract, where they play essential roles in the ionic balance of tubular fluids. CAs are the enzymes responsible for the production of HCO3- which is then transported by membrane transporters to ensure the maturation, storage, and capacitation of the spermatozoa. The transport of H+ is carried out by NHEs, Hv1, and MCTs and is essential for the electrochemical balance and for the maintenance of the pH within the physiological limits along the male reproductive tract. Alterations in HCO3- production and transport of ions have been associated with some male reproductive dysfunctions. Herein, we present an up-to-date review on the distribution and role of the main intervenient on pH homeodynamics in the fluids throughout the male reproductive tract. In addition, we discuss their relevance for the establishment of the male reproductive potential.


Assuntos
Genitália Masculina/metabolismo , Concentração de Íons de Hidrogênio , Animais , Bicarbonatos/metabolismo , Anidrases Carbônicas/metabolismo , Fertilidade , Genitália Masculina/química , Homeostase , Humanos , Canais Iônicos/metabolismo , Bombas de Íon/metabolismo , Masculino , Transportadores de Ácidos Monocarboxílicos/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo
16.
Biochim Biophys Acta Mol Cell Res ; 1865(7): 995-1001, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29694915

RESUMO

In susceptible tumor cells, DNA-damaging antineoplastic agents induce an increase in intracellular pH during the premitochondrial stage of apoptosis. The rate of nonenzymatic deamidation of two asparagines in the anti-apoptotic protein Bcl-xL is accelerated by this increase in pH. Deamidation of these asparagines is a signal for the degradation of Bcl-xL, which is a component of the apoptotic response to DNA damage. It has previously been shown that the increase in pH is mediated by the ion transporter Na+/H+ exchanger 1 in some cells. Here we demonstrate that one or more additional ion transporters also have a role in the regulation of Bcl-xL deamidation in at least some tumor cell lines and fibroblasts. As a second, independent finding, we report that there are histidines in close proximity to the Bcl-xL deamidation sites that are highly conserved in land-dwelling species and we present evidence that deamidation of human Bcl-xL is intramolecularly catalyzed in a manner that is dependent upon these histidines. Further, we present evidence that these histidines act as a pH-sensitive switch that enhances the effect of the increase in pH on the rate of Bcl-xL deamidation. The conservation of such histidines implies that human Bcl-xL is in essence "designed" to be deamidated, which provides further evidence that deamidation serves as a bona fide regulatory post-translational modification of Bcl-xL.


Assuntos
Histidina/química , Bombas de Íon/metabolismo , Proteína bcl-X/química , Proteína bcl-X/metabolismo , Células 3T3 , Animais , Apoptose , Linhagem Celular Tumoral , Dano ao DNA , Desaminação , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Proteína bcl-X/genética
17.
Pflugers Arch ; 471(6): 901-914, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30685787

RESUMO

Fibroblast growth factor 23 (FGF23) levels are elevated in patients with acute kidney injury (AKI). The consequences on renal Ca2+, Mg2+, and Pi regulatory mechanisms are unknown. We hypothesized that renal ischemia-reperfusion (I/R) injury alters the expression of important renal Ca2+, Mg2+, and Pi transport proteins. I/R injury was induced in male C57BL/6 mice by clamping both renal arteries for 27 min. Mice were investigated 18 h later. The mRNA and protein levels of renal Ca2+, Mg2+, and Pi transport proteins were measured by RT-qPCR and western blot analysis. I/R injury-induced hyperphosphatemia and hypermagnesemia were paralleled by a decrease in glomerular filtration rate and an increase in the fractional excretion of Ca2+, Mg2+, and Pi. I/R injury affected the fibroblast growth factor 23 (FGF23)-klotho-vitamin D axis by increasing plasma levels of FGF23 and downregulation of renal klotho expression. Plasma levels of PTH and 1,25-dihydroxyvitamin D3 were unchanged. Further, downregulation of key genes for paracellular reabsorption of Ca2+ and Mg2+ (claudin (Cldn)2, Cldn10b, Cldn16, Cldn19) and for active transcellular transport of Ca2+, Mg2+, and Pi (calbindin-D28K, Ncx1, Pmca4, Cnnm2, Trpm7, NaPi-2a, and NaPi-2c) was observed. However, renal expression of Trpv5 and Trpv6 was increased. In vitro studies support a direct effect of proinflammatory cytokines on the mRNA expression of Cldn16, Cldn19, and Trpv6. Our findings indicate that renal I/R injury increases FGF23 blood levels independent of PTH and 1,25-dihydroxyvitamin D3. This increase is associated with hypermagnesemia, hyperphosphatemia, and increased or decreased expression of specific renal Ca2+, Mg2+, and Pi transporters, respectively.


Assuntos
Injúria Renal Aguda/metabolismo , Bombas de Íon/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Cálcio/metabolismo , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Glucuronidase/metabolismo , Proteínas Klotho , Magnésio/sangue , Masculino , Camundongos Endogâmicos C57BL , Fosfatos/sangue , Vitamina D/metabolismo
18.
Small ; 15(43): e1902189, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31513355

RESUMO

Electronic control of biological processes with bioelectronic devices holds promise for sophisticated regulation of physiology, for gaining fundamental understanding of biological systems, providing new therapeutic solutions, and digitally mediating adaptations of organisms to external factors. The organic electronic ion pump (OEIP) provides a unique means for electronically-controlled, flow-free delivery of ions, and biomolecules at cellular scale. Here, a miniaturized OEIP device based on glass capillary fibers (c-OEIP) is implanted in a biological organism. The capillary form factor at the sub-100 µm scale of the device enables it to be implanted in soft tissue, while its hyperbranched polyelectrolyte channel and addressing protocol allows efficient delivery of a large aromatic molecule. In the first example of an implantable bioelectronic device in plants, the c-OEIP readily penetrates the leaf of an intact tobacco plant with no significant wound response (evaluated up to 24 h) and effectively delivers the hormone abscisic acid (ABA) into the leaf apoplast. OEIP-mediated delivery of ABA, the phytohormone that regulates plant's tolerance to stress, induces closure of stomata, the microscopic pores in leaf's epidermis that play a vital role in photosynthesis and transpiration. Efficient and localized ABA delivery reveals previously unreported kinetics of ABA-induced signal propagation.


Assuntos
Ácido Abscísico/farmacologia , Eletrônica , Bombas de Íon/metabolismo , Nicotiana/fisiologia , Reguladores de Crescimento de Plantas/farmacologia , Estômatos de Plantas/fisiologia , Estômatos de Plantas/efeitos dos fármacos , Nicotiana/efeitos dos fármacos
19.
Biochem Soc Trans ; 47(5): 1247-1257, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31671180

RESUMO

P-type ATPases transport ions across biological membranes against concentration gradients and are essential for all cells. They use the energy from ATP hydrolysis to propel large intramolecular movements, which drive vectorial transport of ions. Tight coordination of the motions of the pump is required to couple the two spatially distant processes of ion binding and ATP hydrolysis. Here, we review our current understanding of the structural dynamics of P-type ATPases, focusing primarily on Ca2+ pumps. We integrate different types of information that report on structural dynamics, primarily time-resolved fluorescence experiments including single-molecule Förster resonance energy transfer and molecular dynamics simulations, and interpret them in the framework provided by the numerous crystal structures of sarco/endoplasmic reticulum Ca2+-ATPase. We discuss the challenges in characterizing the dynamics of membrane pumps, and the likely impact of new technologies on the field.


Assuntos
Bombas de Íon/química , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/química , Trifosfato de Adenosina/metabolismo , Animais , Cálcio/metabolismo , Catálise , Humanos , Hidrólise , Bombas de Íon/metabolismo , Isoenzimas/química , Isoenzimas/metabolismo , Fosforilação , Ligação Proteica , Conformação Proteica , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
20.
Int J Mol Sci ; 20(10)2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31137773

RESUMO

Ion channels and transporters play essential roles in excitable cells including cardiac, skeletal and smooth muscle cells, neurons, and endocrine cells. In pancreatic beta-cells, for example, potassium KATP channels link the metabolic signals generated inside the cell to changes in the beta-cell membrane potential, and ultimately regulate insulin secretion. Mutations in the genes encoding some ion transporter and channel proteins lead to disorders of glucose homeostasis (hyperinsulinaemic hypoglycaemia and different forms of diabetes mellitus). Pancreatic KATP, Non-KATP, and some calcium channelopathies and MCT1 transporter defects can lead to various forms of hyperinsulinaemic hypoglycaemia (HH). Mutations in the genes encoding the pancreatic KATP channels can also lead to different types of diabetes (including neonatal diabetes mellitus (NDM) and Maturity Onset Diabetes of the Young, MODY), and defects in the solute carrier family 2 member 2 (SLC2A2) leads to diabetes mellitus as part of the Fanconi-Bickel syndrome. Variants or polymorphisms in some ion channel genes and transporters have been reported in association with type 2 diabetes mellitus.


Assuntos
Canalopatias/metabolismo , Transtornos do Metabolismo de Glucose/metabolismo , Canais Iônicos/metabolismo , Bombas de Íon/metabolismo , Animais , Canalopatias/genética , Transtornos do Metabolismo de Glucose/genética , Humanos , Canais Iônicos/genética , Bombas de Íon/genética
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