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1.
EMBO Rep ; 23(2): e48754, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-34994490

RESUMO

Mitochondria are unavoidably subject to organellar stress resulting from exposure to a range of reactive molecular species. Consequently, cells operate a poorly understood quality control programme of mitophagy to facilitate elimination of dysfunctional mitochondria. Here, we used a model stressor, deferiprone (DFP), to investigate the molecular basis for stress-induced mitophagy. We show that mitochondrial fission 1 protein (Fis1) is required for DFP-induced mitophagy and that Fis1 is SUMOylated at K149, an amino acid residue critical for Fis1 mitochondrial localization. We find that DFP treatment leads to the stabilization of the SUMO protease SENP3, which is mediated by downregulation of the E3 ubiquitin (Ub) ligase CHIP. SENP3 is responsible for Fis1 deSUMOylation and depletion of SENP3 abolishes DFP-induced mitophagy. Furthermore, preventing Fis1 SUMOylation by conservative K149R mutation enhances Fis1 mitochondrial localization. Critically, expressing a Fis1 K149R mutant restores DFP-induced mitophagy in SENP3-depleted cells. Thus, we propose a model in which SENP3-mediated deSUMOylation facilitates Fis1 mitochondrial localization to underpin stress-induced mitophagy.


Assuntos
Mitocôndrias , Peptídeo Hidrolases , Autofagia , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Mitofagia , Peptídeo Hidrolases/metabolismo
2.
PLoS One ; 16(1): e0243478, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33395404

RESUMO

This study provides regional-scale data on drivers of horseshoe crab (Limulus polyphemus) presence along the northcentral Gulf of Mexico coast and has implications for understanding habitat suitability for sparse horseshoe crab populations of conservation concern worldwide. To collect baseline data on the relationship between environmental factors and presence of horseshoe crabs, we surveyed four sites from the Fort Morgan peninsula of Mobile Bay, Alabama (AL) to Horn Island, Mississippi (MS). We documented number, size and sex of live animals, molts, and carcasses as metrics of horseshoe crab presence and demographics for two years. Data were compared to in situ and remotely sensed environmental attributes to assess environmental drivers of occurrence during the time of study. Overall, greater evidence of horseshoe crab presence was found at western sites (Petit Bois and Horn Islands) compared to eastern sites (Dauphin Island, Fort Morgan peninsula), mediated by a combination of distance from areas of high freshwater discharge and interannual variation in weather. Higher sex ratios also were found associated with higher occurrence, west of Mobile Bay. Land cover, particularly Bare Land and Estuarine Emergent Wetland classes that are common to western sites, was most predictive of live animal and to some extent carcass occurrence. Our findings suggest that small-scale variation in habitat quality can affect occurrence of horseshoe crabs in sparse populations where density is not a limiting factor. Data from molts and carcasses were informative to supplement live animal data and may be useful to enhance ecological assessment and support conservation and management in regions with sparse populations.


Assuntos
Meio Ambiente , Caranguejos Ferradura/fisiologia , Animais , Baías , Tamanho Corporal , Clima , Geografia , Golfo do México , Caranguejos Ferradura/anatomia & histologia , Modelos Lineares , Rios , Razão de Masculinidade , Inquéritos e Questionários , Fatores de Tempo
3.
Semin Cell Dev Biol ; 77: 3-9, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28890422

RESUMO

One of the most interesting features of Arc-dependent synaptic plasticity is how multiple types of synaptic activity can converge to alter Arc transcription and then diverge to induce different plasticity outcomes, ranging from AMPA receptor internalisation that promotes long-term depression (LTD), to actin stabilisation that promotes long-term potentiation (LTP). This diversity suggests that there must be numerous levels of control to ensure the temporal profile, abundance, localisation and function of Arc are appropriately regulated to effect learning and memory in the correct contexts. The activity-dependent transcription and post-translational modification of Arc are crucial regulators of synaptic plasticity, fine-tuning the function of this key protein depending on the specific situation. The extensive cross-talk between signalling pathways and the numerous routes of Arc regulation provide a complex interplay of processes in which Arc-mediated plasticity can be broadly induced, but specifically tailored to synaptic activity. Here we provide an overview what is currently known about these processes and potential future directions.


Assuntos
Proteínas do Citoesqueleto/biossíntese , Proteínas do Citoesqueleto/genética , Regulação da Expressão Gênica/genética , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Plasticidade Neuronal/genética , Processamento de Proteína Pós-Traducional/genética , Transcrição Gênica/genética , Animais , Sinalização do Cálcio/fisiologia , AMP Cíclico/metabolismo , Humanos , Aprendizagem/fisiologia , Memória/fisiologia , Camundongos , Plasticidade Neuronal/fisiologia , Ratos , Receptores de AMPA/metabolismo , Sumoilação , Ubiquitinação
4.
PLoS One ; 10(5): e0126538, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25992681

RESUMO

A northern Gulf of Mexico (GoM) cetacean unusual mortality event (UME) involving primarily bottlenose dolphins (Tursiops truncatus) in Louisiana, Mississippi, and Alabama began in February 2010 and continued into 2014. Overlapping in time and space with this UME was the Deepwater Horizon (DWH) oil spill, which was proposed as a contributing cause of adrenal disease, lung disease, and poor health in live dolphins examined during 2011 in Barataria Bay, Louisiana. To assess potential contributing factors and causes of deaths for stranded UME dolphins from June 2010 through December 2012, lung and adrenal gland tissues were histologically evaluated from 46 fresh dead non-perinatal carcasses that stranded in Louisiana (including 22 from Barataria Bay), Mississippi, and Alabama. UME dolphins were tested for evidence of biotoxicosis, morbillivirus infection, and brucellosis. Results were compared to up to 106 fresh dead stranded dolphins from outside the UME area or prior to the DWH spill. UME dolphins were more likely to have primary bacterial pneumonia (22% compared to 2% in non-UME dolphins, P = .003) and thin adrenal cortices (33% compared to 7% in non-UME dolphins, P = .003). In 70% of UME dolphins with primary bacterial pneumonia, the condition either caused or contributed significantly to death. Brucellosis and morbillivirus infections were detected in 7% and 11% of UME dolphins, respectively, and biotoxin levels were low or below the detection limit, indicating that these were not primary causes of the current UME. The rare, life-threatening, and chronic adrenal gland and lung diseases identified in stranded UME dolphins are consistent with exposure to petroleum compounds as seen in other mammals. Exposure of dolphins to elevated petroleum compounds present in coastal GoM waters during and after the DWH oil spill is proposed as a cause of adrenal and lung disease and as a contributor to increased dolphin deaths.


Assuntos
Doenças das Glândulas Suprarrenais/mortalidade , Glândulas Suprarrenais/patologia , Golfinho Nariz-de-Garrafa , Brucelose/mortalidade , Pulmão/patologia , Poluição por Petróleo/efeitos adversos , Pneumonia Bacteriana/mortalidade , Doenças das Glândulas Suprarrenais/etiologia , Doenças das Glândulas Suprarrenais/patologia , Animais , Golfinho Nariz-de-Garrafa/microbiologia , Golfinho Nariz-de-Garrafa/virologia , Brucelose/etiologia , Brucelose/microbiologia , Brucelose/patologia , Feminino , Golfo do México , Louisiana , Masculino , Infecções por Morbillivirus/etiologia , Infecções por Morbillivirus/mortalidade , Infecções por Morbillivirus/patologia , Infecções por Morbillivirus/virologia , Mortalidade , Pneumonia Bacteriana/etiologia , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/patologia
5.
PLoS One ; 9(3): e91683, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24670971

RESUMO

The explosion of the Deepwater Horizon drilling platform created the largest marine oil spill in U.S. history. As part of the Natural Resource Damage Assessment process, we applied an innovative modeling approach to obtain upper estimates for occupancy and for number of manatees in areas potentially affected by the oil spill. Our data consisted of aerial survey counts in waters of the Florida Panhandle, Alabama and Mississippi. Our method, which uses a Bayesian approach, allows for the propagation of uncertainty associated with estimates from empirical data and from the published literature. We illustrate that it is possible to derive estimates of occupancy rate and upper estimates of the number of manatees present at the time of sampling, even when no manatees were observed in our sampled plots during surveys. We estimated that fewer than 2.4% of potentially affected manatee habitat in our Florida study area may have been occupied by manatees. The upper estimate for the number of manatees present in potentially impacted areas (within our study area) was estimated with our model to be 74 (95%CI 46 to 107). This upper estimate for the number of manatees was conditioned on the upper 95%CI value of the occupancy rate. In other words, based on our estimates, it is highly probable that there were 107 or fewer manatees in our study area during the time of our surveys. Because our analyses apply to habitats considered likely manatee habitats, our inference is restricted to these sites and to the time frame of our surveys. Given that manatees may be hard to see during aerial surveys, it was important to account for imperfect detection. The approach that we described can be useful for determining the best allocation of resources for monitoring and conservation.


Assuntos
Ecossistema , Monitoramento Ambiental , Poluição por Petróleo , Trichechus/fisiologia , Alabama , Animais , Florida , Geografia , Mississippi , Inquéritos e Questionários
6.
Neuromolecular Med ; 15(4): 692-706, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23934328

RESUMO

Timely and efficient information transfer at synapses is fundamental to brain function. Synapses are highly dynamic structures that exhibit long-lasting activity-dependent alterations to their structure and transmission efficiency, a phenomenon termed synaptic plasticity. These changes, which occur through alterations in presynaptic release or in the trafficking of postsynaptic receptor proteins, underpin the formation and stabilisation of neural circuits during brain development, and encode, process and store information essential for learning, memory and cognition. In recent years, it has emerged that the ubiquitin-like posttranslational modification SUMOylation is an important mediator of several aspects of neuronal and synaptic function. Through orchestrating synapse formation, presynaptic release and the trafficking of postsynaptic receptor proteins during forms of synaptic plasticity such as long-term potentiation, long-term depression and homeostatic scaling, SUMOylation is being increasingly appreciated to play a central role in neurotransmission. In this review, we outline key discoveries in this relatively new field, provide an update on recent progress regarding the targets and consequences of protein SUMOylation in synaptic function and plasticity, and highlight key outstanding questions regarding the roles of protein SUMOylation in the brain.


Assuntos
Proteínas do Tecido Nervoso/fisiologia , Plasticidade Neuronal , Transporte Proteico/fisiologia , Receptores de Neurotransmissores/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/fisiologia , Sumoilação/fisiologia , Transmissão Sináptica/fisiologia , Animais , Quinase 3 da Glicogênio Sintase/fisiologia , Glicogênio Sintase Quinase 3 beta , Guanilato Quinases/fisiologia , Humanos , Fatores de Transcrição MEF2/fisiologia , Neurogênese , Neurônios/metabolismo , PTEN Fosfo-Hidrolase/fisiologia , Canais de Potássio/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Receptores de Ácido Caínico/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Receptores Pré-Sinápticos/fisiologia , Complexos Ubiquitina-Proteína Ligase/fisiologia
7.
Environ Sci Technol ; 46(23): 12787-95, 2012 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-23131011

RESUMO

During and after the Deepwater Horizon Oil Spill (DWHOS), oysters (Crassostrea virginica) were exposed to oil and susceptible to incidental consumption of surface and subsurface oil materials. We determined the contribution of oil materials from the DWHOS to diet of oysters by comparing carbon (C) and nitrogen (N) stable isotope ratios in oyster shell to ratios in suspended particulate matter (SPM) and in fresh and weathered oil. Average δ(13)C and δ(15)N values in oyster shell (-21 ± 1‰ and 9-11‰, respectively) were consistent with consumption of naturally available SPM as opposed to values in oil (-27 ± 0.2‰, 1.6 ± 0.4‰). Stable isotope ratios in oyster adductor muscle were similar to shell for δ(15)N but not δ(13)C, suggesting either a recent shift in diet composition or differential assimilation of C between tissue types. We found no evidence of assimilation of oil-derived C and N and, therefore, no evidence of an oyster-based conduit to higher trophic levels. Trace elements in shell were inconclusive to corroborate oil exposure. These findings are not an indication that oysters were not exposed to oil; rather they imply oysters either did not consume oil-derived materials or consumed too little to be detectable compared to natural diet.


Assuntos
Crassostrea/metabolismo , Monitoramento Ambiental , Poluição por Petróleo/análise , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/metabolismo , Animais , Isótopos de Carbono/análise , Isótopos de Carbono/metabolismo , Isótopos de Nitrogênio/análise , Isótopos de Nitrogênio/metabolismo , Material Particulado/análise , Material Particulado/metabolismo
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