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1.
Glob Chang Biol ; 30(1): e17139, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38273498

RESUMO

Permafrost degradation in peatlands is altering vegetation and soil properties and impacting net carbon storage. We studied four adjacent sites in Alaska with varied permafrost regimes, including a black spruce forest on a peat plateau with permafrost, two collapse scar bogs of different ages formed following thermokarst, and a rich fen without permafrost. Measurements included year-round eddy covariance estimates of net carbon dioxide (CO2 ), mid-April to October methane (CH4 ) emissions, and environmental variables. From 2011 to 2022, annual rainfall was above the historical average, snow water equivalent increased, and snow-season duration shortened due to later snow return. Seasonally thawed active layer depths also increased. During this period, all ecosystems acted as slight annual sources of CO2 (13-59 g C m-2 year-1 ) and stronger sources of CH4 (11-14 g CH4 m-2 from ~April to October). The interannual variability of net ecosystem exchange was high, approximately ±100 g C m-2 year-1 , or twice what has been previously reported across other boreal sites. Net CO2 release was positively related to increased summer rainfall and winter snow water equivalent and later snow return. Controls over CH4 emissions were related to increased soil moisture and inundation status. The dominant emitter of carbon was the rich fen, which, in addition to being a source of CO2 , was also the largest CH4 emitter. These results suggest that the future carbon-source strength of boreal lowlands in Interior Alaska may be determined by the area occupied by minerotrophic fens, which are expected to become more abundant as permafrost thaw increases hydrologic connectivity. Since our measurements occur within close proximity of each other (≤1 km2 ), this study also has implications for the spatial scale and data used in benchmarking carbon cycle models and emphasizes the necessity of long-term measurements to identify carbon cycle process changes in a warming climate.


Assuntos
Ecossistema , Pergelissolo , Dióxido de Carbono/análise , Metano , Solo , Água
2.
Proc Natl Acad Sci U S A ; 117(34): 20438-20446, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32778585

RESUMO

Northern peatlands have accumulated large stocks of organic carbon (C) and nitrogen (N), but their spatial distribution and vulnerability to climate warming remain uncertain. Here, we used machine-learning techniques with extensive peat core data (n > 7,000) to create observation-based maps of northern peatland C and N stocks, and to assess their response to warming and permafrost thaw. We estimate that northern peatlands cover 3.7 ± 0.5 million km2 and store 415 ± 150 Pg C and 10 ± 7 Pg N. Nearly half of the peatland area and peat C stocks are permafrost affected. Using modeled global warming stabilization scenarios (from 1.5 to 6 °C warming), we project that the current sink of atmospheric C (0.10 ± 0.02 Pg C⋅y-1) in northern peatlands will shift to a C source as 0.8 to 1.9 million km2 of permafrost-affected peatlands thaw. The projected thaw would cause peatland greenhouse gas emissions equal to ∼1% of anthropogenic radiative forcing in this century. The main forcing is from methane emissions (0.7 to 3 Pg cumulative CH4-C) with smaller carbon dioxide forcing (1 to 2 Pg CO2-C) and minor nitrous oxide losses. We project that initial CO2-C losses reverse after ∼200 y, as warming strengthens peatland C-sinks. We project substantial, but highly uncertain, additional losses of peat into fluvial systems of 10 to 30 Pg C and 0.4 to 0.9 Pg N. The combined gaseous and fluvial peatland C loss estimated here adds 30 to 50% onto previous estimates of permafrost-thaw C losses, with southern permafrost regions being the most vulnerable.

3.
Wetlands (Wilmington) ; 43(8): 105, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38037553

RESUMO

Wetlands cover a small portion of the world, but have disproportionate influence on global carbon (C) sequestration, carbon dioxide and methane emissions, and aquatic C fluxes. However, the underlying biogeochemical processes that affect wetland C pools and fluxes are complex and dynamic, making measurements of wetland C challenging. Over decades of research, many observational, experimental, and analytical approaches have been developed to understand and quantify pools and fluxes of wetland C. Sampling approaches range in their representation of wetland C from short to long timeframes and local to landscape spatial scales. This review summarizes common and cutting-edge methodological approaches for quantifying wetland C pools and fluxes. We first define each of the major C pools and fluxes and provide rationale for their importance to wetland C dynamics. For each approach, we clarify what component of wetland C is measured and its spatial and temporal representativeness and constraints. We describe practical considerations for each approach, such as where and when an approach is typically used, who can conduct the measurements (expertise, training requirements), and how approaches are conducted, including considerations on equipment complexity and costs. Finally, we review key covariates and ancillary measurements that enhance the interpretation of findings and facilitate model development. The protocols that we describe to measure soil, water, vegetation, and gases are also relevant for related disciplines such as ecology. Improved quality and consistency of data collection and reporting across studies will help reduce global uncertainties and develop management strategies to use wetlands as nature-based climate solutions. Supplementary Information: The online version contains supplementary material available at 10.1007/s13157-023-01722-2.

4.
Proc Natl Acad Sci U S A ; 116(11): 4822-4827, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30804186

RESUMO

Glacial-interglacial variations in CO2 and methane in polar ice cores have been attributed, in part, to changes in global wetland extent, but the wetland distribution before the Last Glacial Maximum (LGM, 21 ka to 18 ka) remains virtually unknown. We present a study of global peatland extent and carbon (C) stocks through the last glacial cycle (130 ka to present) using a newly compiled database of 1,063 detailed stratigraphic records of peat deposits buried by mineral sediments, as well as a global peatland model. Quantitative agreement between modeling and observations shows extensive peat accumulation before the LGM in northern latitudes (>40°N), particularly during warmer periods including the last interglacial (130 ka to 116 ka, MIS 5e) and the interstadial (57 ka to 29 ka, MIS 3). During cooling periods of glacial advance and permafrost formation, the burial of northern peatlands by glaciers and mineral sediments decreased active peatland extent, thickness, and modeled C stocks by 70 to 90% from warmer times. Tropical peatland extent and C stocks show little temporal variation throughout the study period. While the increased burial of northern peats was correlated with cooling periods, the burial of tropical peat was predominately driven by changes in sea level and regional hydrology. Peat burial by mineral sediments represents a mechanism for long-term terrestrial C storage in the Earth system. These results show that northern peatlands accumulate significant C stocks during warmer times, indicating their potential for C sequestration during the warming Anthropocene.

5.
Clin Infect Dis ; 71(7): 1715-1722, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-32009165

RESUMO

BACKGROUND: People who inject drugs have a high prevalence of hepatitis C virus (HCV) and significant disease associated with drug use; however, HCV treatment often occurs in absence of interventions to address opioid use disorder and drug use-related harms. The impact of concurrent initiation of opioid agonist therapy (OAT) on HCV treatment and drug use outcomes is unknown. METHODS: In this prospective, open-label, observational trial at a harm reduction organization's drop-in center in Washington, DC, 100 patients with chronic HCV infection, opioid use disorder, and ongoing injection drug use were treated with sofosbuvir-velpatasvir for 12-weeks and offered buprenorphine initiation. The primary end point was sustained virologic response (SVR), and secondary end points included uptake of and retention in OAT, change in risk behavior, and determinants of SVR. RESULTS: Eighty-two patients (82%) achieved SVR, which was not associated with baseline OAT status (P = .33), on-treatment drug use (P >.99), or imperfect daily adherence (P = .35) but was significantly associated with completing 2 or more 28-pill bottles of sofosbuvir-velpatasvir (P < .001) and receiving OAT at week 24 (P = .01). Of 67 patients not already receiving OAT at baseline, 53 (79%) started OAT. At week 24, 68 (68%) patients were receiving OAT. Receipt of OAT was associated with fewer opiate-positive urine drug screens (P = .003), lower human immunodeficiency virus risk-taking behavior scores (P < .001), and lower rates of opioid overdose (P = .04). CONCLUSIONS: The Novel Model of Hepatitis C Treatment as an Anchor to Prevent HIV, Initiate Opioid Agonist Therapy, and Reduce Risky Behavior study demonstrates high uptake of buprenorphine collocated with HCV treatment, and it shows that concurrent initiation of OAT with HCV treatment can result in high rates of SVR while reducing risks associated with drug use. CLINICAL TRIALS REGISTRATION: NCT03221309.


Assuntos
Hepatite C , Transtornos Relacionados ao Uso de Opioides , Preparações Farmacêuticas , Abuso de Substâncias por Via Intravenosa , Antivirais/uso terapêutico , Hepacivirus , Hepatite C/tratamento farmacológico , Humanos , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/complicações , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Estudos Prospectivos , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/tratamento farmacológico
7.
Glob Chang Biol ; 23(3): 1109-1127, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27362936

RESUMO

Permafrost peatlands store one-third of the total carbon (C) in the atmosphere and are increasingly vulnerable to thaw as high-latitude temperatures warm. Large uncertainties remain about C dynamics following permafrost thaw in boreal peatlands. We used a chronosequence approach to measure C stocks in forested permafrost plateaus (forest) and thawed permafrost bogs, ranging in thaw age from young (<10 years) to old (>100 years) from two interior Alaska chronosequences. Permafrost originally aggraded simultaneously with peat accumulation (syngenetic permafrost) at both sites. We found that upon thaw, C loss of the forest peat C is equivalent to ~30% of the initial forest C stock and is directly proportional to the prethaw C stocks. Our model results indicate that permafrost thaw turned these peatlands into net C sources to the atmosphere for a decade following thaw, after which post-thaw bog peat accumulation returned sites to net C sinks. It can take multiple centuries to millennia for a site to recover its prethaw C stocks; the amount of time needed for them to regain their prethaw C stocks is governed by the amount of C that accumulated prior to thaw. Consequently, these findings show that older peatlands will take longer to recover prethaw C stocks, whereas younger peatlands will exceed prethaw stocks in a matter of centuries. We conclude that the loss of sporadic and discontinuous permafrost by 2100 could result in a loss of up to 24 Pg of deep C from permafrost peatlands.


Assuntos
Carbono , Pergelissolo , Alaska , Florestas , Solo , Áreas Alagadas
8.
Proc Natl Acad Sci U S A ; 107(16): 7347-52, 2010 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-20368451

RESUMO

Northern peatlands represent one of the largest biospheric carbon (C) reservoirs; however, the role of peatlands in the global carbon cycle remains intensely debated, owing in part to the paucity of detailed regional datasets and the complexity of the role of climate, ecosystem processes, and environmental factors in controlling peatland C dynamics. Here we used detailed C accumulation data from four peatlands and a compilation of peatland initiation ages across Alaska to examine Holocene peatland dynamics and climate sensitivity. We find that 75% of dated peatlands in Alaska initiated before 8,600 years ago and that early Holocene C accumulation rates were four times higher than the rest of the Holocene. Similar rapid peatland expansion occurred in West Siberia during the Holocene thermal maximum (HTM). Our results suggest that high summer temperature and strong seasonality during the HTM in Alaska might have played a major role in causing the highest rates of C accumulation and peatland expansion. The rapid peatland expansion and C accumulation in these vast regions contributed significantly to the peak of atmospheric methane concentrations in the early Holocene. Furthermore, we find that Alaskan peatlands began expanding much earlier than peatlands in other regions, indicating an important contribution of these peatlands to the pre-Holocene increase in atmospheric methane concentrations.


Assuntos
Carbono/química , Solo , Alaska , Atmosfera , Ecossistema , Geologia/métodos , Temperatura Alta , Metano/química , Modelos Biológicos , Datação Radiométrica , Estações do Ano , Sibéria , Temperatura
9.
J Addict Med ; 16(1): 10-17, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33560694

RESUMO

OBJECTIVE: The ANCHOR program offered buprenorphine treatment to people who inject drugs engaged in hepatitis C (HCV) treatment at a Washington, DC harm reduction organization. This analysis describes the program model and outcomes of the opioid care continuum at 1 year. METHODS: Primary outcomes were initiation of buprenorphine and retention in care, defined by an active buprenorphine prescription at given time points. Secondary outcomes included treatment interruptions, reasons for treatment noninitiation and termination, buprenorphine and opiate use, and HIV risk behaviors. Buprenorphine and opiate use were measured by urine toxicology screens and HIV risk behavior was quantified using a validated survey. RESULTS: Of 67 patients receiving HCV treatment not on opioid agonist therapy at baseline, 96% (n = 64) were interested and 73% (n = 49) initiated buprenorphine. Retention was 82% (n = 40), 65% (n = 32), and 59% (n = 29) at months 1, 6, and 12, respectively. Retention at 12 months was associated with self-reported engagement in routine medical care (P < 0.01), but was not associated with gender, stable housing, past opioid agonist therapy, or past overdose. Among retained patients, urine screens positive for opioids were 73% (n = 29), 56% (n = 18), and 79% (n = 23) at months 1, 6, and 12. There was a significant mean decrease in HIV risk-taking behavior scores over the treatment period, primarily driven by reduced injection frequency. CONCLUSIONS: Patients engaged in HCV treatment at a harm reduction organization showed a high rate of initiation of buprenorphine treatment, with retention comparable to other treatment settings. Although most patients continued using opioids on treatment, there was a reduced frequency of injection drug use, a significant driver of OUD-related risk. These data support the use of low-threshold buprenorphine access alongside HCV treatment to reduce morbidity and mortality in people with OUD.


Assuntos
Buprenorfina , Hepatite C , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/uso terapêutico , Buprenorfina/uso terapêutico , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Humanos , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/terapia
10.
Aliment Pharmacol Ther ; 55(9): 1160-1168, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35247000

RESUMO

BACKGROUND: The British Society of Gastroenterology has recommended the Edinburgh Dysphagia Score (EDS) to risk-stratify dysphagia referrals during the endoscopy COVID recovery phase. AIMS: External validation of the diagnostic accuracy of EDS and exploration of potential changes to improve its diagnostic performance. METHODS: A prospective multicentre study of consecutive patients referred with dysphagia on an urgent suspected upper gastrointestinal (UGI) cancer pathway between May 2020 and February 2021. The sensitivity and negative predictive value (NPV) of EDS were calculated. Variables associated with UGI cancer were identified by forward stepwise logistic regression and a modified Cancer Dysphagia Score (CDS) developed. RESULTS: 1301 patients were included from 19 endoscopy providers; 43% male; median age 62 (IQR 51-73) years. 91 (7%) UGI cancers were diagnosed, including 80 oesophageal, 10 gastric and one duodenal cancer. An EDS ≥3.5 had a sensitivity of 96.7 (95% CI 90.7-99.3)% and an NPV of 99.3 (97.8-99.8)%. Age, male sex, progressive dysphagia and unintentional weight loss >3 kg were positively associated and acid reflux and localisation to the neck were negatively associated with UGI cancer. Dysphagia duration <6 months utilised in EDS was replaced with progressive dysphagia in CDS. CDS ≥5.5 had a sensitivity of 97.8 (92.3-99.7)% and NPV of 99.5 (98.1-99.9)%. Area under receiver operating curve was 0.83 for CDS, compared to 0.81 for EDS. CONCLUSIONS: In a national cohort, the EDS has high sensitivity and NPV as a triage tool for UGI cancer. The CDS offers even higher diagnostic accuracy. The EDS or CDS should be incorporated into the urgent suspected UGI cancer pathway.


Assuntos
COVID-19 , Transtornos de Deglutição , Neoplasias Gastrointestinais , Idoso , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Endoscopia Gastrointestinal , Feminino , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Encaminhamento e Consulta , Triagem
11.
Open Forum Infect Dis ; 9(3): ofab658, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35187191

RESUMO

BACKGROUND: Daily oral preexposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) prevents human immunodeficiency (HIV) among people who inject drugs (PWID). Despite rising HIV incidence and injection drug use (IDU), PrEP use remains low and there is limited research about uptake, adherence, and retention among PWID. METHODS: The ANCHOR investigation evaluated a community-based care model collocating hepatitis C virus (HCV) treatment, medication for opioid use disorder (OUD), and PrEP in individuals in Washington, DC, and Baltimore, Maryland. PrEP counseling was conducted from HCV treatment day 0 until week 24. Subjects could start any time during this window, were followed for 48 weeks, and were assessed for adherence by self-report and dried blood spot TDF analysis. RESULTS: One hundred ninety-eight participants were enrolled, of whom 185 (93%) were HIV negative. Twenty-nine individuals (15.7% of HIV-negative cohort) initiated PrEP. One hundred sixteen participants (62.7%) met 2014 Centers for Disease Control and Prevention (CDC) PrEP criteria due to IDU (82 [44.3%]), sex (9 [4.9%]), or both practices (25 [13.5%]). Providers recommended PrEP to 94 individuals (50.8%), and recommendation was associated with PrEP uptake. Median treatment duration was 104 days (interquartile range, 28-276 days), with 8 participants retained through week 48. Adherence was variable over time by self-report and declined by TDF analysis. No HIV seroconversions occurred. CONCLUSIONS: This cohort of people with HCV and OUD experienced low uptake of PrEP despite the majority meeting CDC criteria. High rates of disruption and discontinuation, compounded by variable adherence, made TDF/FTC a suboptimal prevention strategy. Emerging modalities like long-acting formulations may address these barriers, but PWID have been excluded from their development to date.

12.
Nat Commun ; 13(1): 4959, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-36002465

RESUMO

High-latitude peatlands are changing rapidly in response to climate change, including permafrost thaw. Here, we reconstruct hydrological conditions since the seventeenth century using testate amoeba data from 103 high-latitude peat archives. We show that 54% of the peatlands have been drying and 32% have been wetting over this period, illustrating the complex ecohydrological dynamics of high latitude peatlands and their highly uncertain responses to a warming climate.


Assuntos
Amoeba , Pergelissolo , Mudança Climática , Hidrologia , Solo
13.
Nat Commun ; 12(1): 4786, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373455

RESUMO

Salmonella enterica serovar 4,[5],12:i:- (Salmonella 4,[5],12:i:-) is a monophasic variant of Salmonella Typhimurium that has emerged as a global cause of multidrug resistant salmonellosis. We used Bayesian phylodynamics, genomic epidemiology, and phenotypic characterization to describe the emergence and evolution of Salmonella 4,[5],12:i:- in Australia. We show that the interruption of the genetic region surrounding the phase II flagellin, FljB, causing a monophasic phenotype, represents a stepwise evolutionary event through the accumulation of mobile resistance elements with minimal impairment to bacterial fitness. We identify three lineages with different population dynamics and discrete antimicrobial resistance profiles emerged, likely reflecting differential antimicrobial selection pressures. Two lineages are associated with travel to South-East Asia and the third lineage is endemic to Australia. Moreover antimicrobial-resistant Salmonella 4,[5],12:i- lineages efficiently infected and survived in host phagocytes and epithelial cells without eliciting significant cellular cytotoxicity, suggesting a suppression of host immune response that may facilitate the persistence of Salmonella 4,[5],12:i:-.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Evolução Molecular , Salmonella enterica/classificação , Salmonella enterica/genética , Sorogrupo , Antibacterianos/farmacologia , Austrália , Teorema de Bayes , Linhagem Celular , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Flagelina/genética , Humanos , Imunidade , Metais Pesados/farmacologia , Filogenia , Salmonella enterica/efeitos dos fármacos , Salmonella typhimurium , Células THP-1 , Sequenciamento Completo do Genoma
14.
Sci Adv ; 6(36)2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32917607

RESUMO

Anomalously low winter sea ice extent and early retreat in CE 2018 and 2019 challenge previous notions that winter sea ice in the Bering Sea has been stable over the instrumental record, although long-term records remain limited. Here, we use a record of peat cellulose oxygen isotopes from St. Matthew Island along with isotope-enabled general circulation model (IsoGSM) simulations to generate a 5500-year record of Bering Sea winter sea ice extent. Results show that over the last 5500 years, sea ice in the Bering Sea decreased in response to increasing winter insolation and atmospheric CO2, suggesting that the North Pacific is highly sensitive to small changes in radiative forcing. We find that CE 2018 sea ice conditions were the lowest of the last 5500 years, and results suggest that sea ice loss may lag changes in CO2 concentrations by several decades.

15.
Nat Commun ; 10(1): 3231, 2019 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324773

RESUMO

Sediment cores from Florida Bay, Everglades National Park were examined to determine ecosystem response to relative sea-level rise (RSLR) over the Holocene. High-resolution multiproxy analysis from four sites show freshwater wetlands transitioned to mangrove environments 4-3.6 ka, followed by estuarine environments 3.4-2.8 ka, during a period of enhanced climate variability. We calculate a RSLR rate of 0.67 ± 0.1 mm yr-1 between ~4.2-2.8 ka, 4-6 times lower than current rates. Despite low RSLR rates, the rapid mangrove to estuarine transgression was facilitated by a period of prolonged droughts and frequent storms. These findings suggest that with higher and accelerating RSLR today, enhanced climate variability could further hasten the loss of mangrove-lined coastlines, compounded by the reductions in natural flow to the coast caused by water management. Climate variability is nonlinear, and when superimposed on increases in RSLR, can complicate estimated trajectories of coastal inundation for resource management and urban planning.

16.
Am J Pathol ; 163(4): 1457-65, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14507653

RESUMO

Complement activation during ischemia and reperfusion contributes to the development of tissue injury with severe negative impact on outcomes in transplantation. To counter the effect of complement, we present a strategy to deliver a novel complement regulator stabilized on cell surfaces within donor organs. The membrane-bound complement regulator is able to inhibit complement activation when the donor organ is revascularized and exposed to host-circulating complement. Application of this construct to donor kidneys protected transplanted tissues from ischemia/reperfusion injury and reduced the deposition of activated complement and histological signs of damage under conditions in which a nontargeted control construct was ineffective. Treatment of donor organs in this way improved graft performance in the short and long term. An analysis of the immune response in allograft recipients showed that reducing graft damage at the time of transplantation through complement regulation also modulated the alloresponse. Additionally, the results of perfusion studies with human kidneys demonstrated the feasibility of targeting endothelial and epithelial surfaces with this construct, to allow investigation in clinical transplantation.


Assuntos
Transplante de Rim , Rim/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Receptores de Complemento 3b/química , Circulação Renal , Traumatismo por Reperfusão/prevenção & controle , Doença Aguda , Animais , Doença Crônica , Endotélio/metabolismo , Endotélio/patologia , Células Epiteliais/metabolismo , Rejeição de Enxerto/fisiopatologia , Rejeição de Enxerto/prevenção & controle , Humanos , Técnicas In Vitro , Rim/metabolismo , Rim/fisiopatologia , Nefropatias/prevenção & controle , Fragmentos de Peptídeos/metabolismo , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Receptores de Superfície Celular/metabolismo , Doadores de Tecidos
17.
J Am Soc Nephrol ; 14(8 Suppl 3): S290-6, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12874448

RESUMO

Biotin-cysteine was used to study protein S-thiolation in isolated rat kidneys subjected to ischemia and reperfusion. After 40 min of ischemia, total protein S-thiolation increased significantly (P < 0.05), by 311%, and remained significantly elevated (P < 0.05), 221% above control, after 5 min of postischemic reperfusion. Treatment of protein samples with 2-mercaptoethanol abolished the S-thiolation signals detected, consistent with the dependence of the signal on the presence of a disulfide bond. With the use of gel filtration chromatography followed by affinity purification with streptavidin-agarose, S-thiolated proteins were purified from CHAPS-soluble kidney homogenate. The proteins were then separated by SDS-PAGE and stained with Coomassie blue. With a combination of matrix-assisted laser desorption ionization time of flight mass spectrometry and LC/MS/MS analysis of protein bands digested with trypsin, a number of S-thiolation substrates were identified. These included the LDL receptor-related protein 2, ATP synthase alpha chain, heat shock protein 90 beta, hydroxyacid oxidase 3, serum albumin precursor, triose phosphate isomerase, and lamin. These represent proteins that may be functionally regulated by S-thiolation and thus could undergo a change in activity or function after renal ischemia and reperfusion.


Assuntos
Cisteína/metabolismo , Rim/metabolismo , Estresse Oxidativo , Proteínas/metabolismo , Circulação Renal , Traumatismo por Reperfusão/metabolismo , Animais , Técnicas In Vitro , Masculino , Oxirredução , Proteínas/química , Ratos , Ratos Endogâmicos , Especificidade por Substrato , Compostos de Sulfidrila/metabolismo
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