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1.
Curr Oncol ; 31(2): 733-746, 2024 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-38392048

RESUMO

Whilst existing quantitative research identifies outcomes believed to be important by researchers and clinicians, it may neglect outcomes that are meaningful to patients. This study aimed to explore the outcomes of exercise that are important to people with lung cancer and their carers. Data collection involved a qualitative methodology including semi-structured interviews and focus groups. Question guide development was informed by the International Classification of Functioning (ICF) framework. Data were analyzed by two researchers with NVivo (v12) software using a conventional content analysis process, followed by directed content analysis to map outcomes to the ICF. Conduct and reporting adhered to COREQ guidelines. Fifteen participants provided data. Most participants had received their diagnoses 24 months prior to study involvement (n = 9), and one-third had completed treatment (n = 5). Important outcomes were reported by participants across all domains of the ICF: activity and participation (n = 24), body function (n = 19), body structure (n = 5), environmental factors (n = 5), and personal factors (n = 1). Additional code categories pertained to the impacts of non-cancer factors such as age, frailty, and comorbidities; identifying barriers to exercise; and individualizing outcome measures. Clinicians and researchers should consider selecting outcomes from all relevant domains of the ICF, with a focus on the activity and participation domain, in addition to non-cancer factors such as ageing, frailty, and co-morbidities. Feedback should be provided to patients following outcome measures collection and reassessment.


Assuntos
Fragilidade , Neoplasias Pulmonares , Humanos , Classificação Internacional de Funcionalidade, Incapacidade e Saúde , Neoplasias Pulmonares/terapia , Pesquisa Qualitativa , Grupos Focais
2.
SLAS Technol ; 28(5): 375-379, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37327946

RESUMO

Laboratory automation uses large amounts of plastic consumables, generating substantial single-use plastic waste. Automated ELISAs are an indispensable analytical tool in vaccine formulation and process development. Current workflows, however, rely on disposable liquid handling tips. In progress toward sustainability, we developed workflows for washing 384-well format liquid handling tips, using nontoxic reagents, for re-use during ELISA testing. We estimate that this workflow reduces plastic and cardboard waste in our facility by 989 kg/year and 202 kg/year, respectively, without introducing new chemicals into our waste steam.

3.
Eur J Drug Metab Pharmacokinet ; 48(3): 311-327, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37086340

RESUMO

BACKGROUND AND OBJECTIVE: N,N-dimethyltryptamine (DMT) is a psychedelic compound under development for the treatment of major depressive disorder (MDD). This study evaluated the preclinical and clinical pharmacokinetics and metabolism of DMT in healthy subjects. METHODS: The physiochemical properties of DMT were determined using a series of in vitro experiments and its metabolic profile was assessed using monoamine oxidase (MAO) and cytochrome P450 (CYP) inhibitors in hepatocyte and mitochondrial fractions. Clinical pharmacokinetics results are from the phase I component of a phase I/IIa randomised, double-blind, placebo-controlled, parallel-group, dose-escalation trial (NCT04673383). Healthy adults received single escalating doses of DMT fumarate (SPL026) via a two-phase intravenous (IV) infusion. Dosing regimens were calculated based on pharmacokinetic modelling and predictions with progression to each subsequent dose level contingent upon safety and tolerability. RESULTS: In vitro clearance of DMT was reduced through the inhibition of MAO-A, CYP2D6 and to a lesser extent CYP2C19. Determination of lipophilicity and plasma protein binding was low, indicating that a high proportion of DMT is available for distribution and metabolism, consistent with the very rapid clinical pharmacokinetics. Twenty-four healthy subjects received escalating doses of DMT administered as a 10-min infusion over the dose range of 9-21.5 mg (DMT freebase). DMT was rapidly cleared for all doses: mean elimination half-life was 9-12 min. All doses were safe and well tolerated and there was no relationship between peak DMT plasma concentrations and body mass index (BMI) or weight. CONCLUSION: This is the first study to determine, in detail, the full pharmacokinetics profile of DMT following a slow IV infusion in humans, confirming rapid attainment of peak plasma concentrations followed by rapid clearance. These findings provide evidence which supports the development of novel DMT infusion regimens for the treatment of MDD. CLINICAL TRIAL REGISTRATION: Registered on ClinicalTrials.gov (NCT04673383).


Assuntos
Transtorno Depressivo Maior , N,N-Dimetiltriptamina , Adulto , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Citocromo P-450 CYP2D6/metabolismo , Monoaminoxidase/metabolismo , Cinética , Método Duplo-Cego , Relação Dose-Resposta a Droga
4.
J Clin Med ; 12(5)2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36902659

RESUMO

BACKGROUND: Growing evidence supports exercise for people with lung cancer. This overview aimed to summarise exercise intervention efficacy and safety across the care continuum. METHODS: Eight databases (including Cochrane and Medline) were searched (inception-February 2022) for systematic reviews of RCTs/quasi-RCTs. Eligibility: population-adults with lung cancer; intervention: exercise (e.g., aerobic, resistance) +/- non-exercise (e.g., nutrition); comparator: usual care/non-exercise; primary outcomes: exercise capacity, physical function, health-related quality of life (HRQoL) and post-operative complications. Duplicate, independent title/abstract and full-text screening, data extraction and quality ratings (AMSTAR-2) were completed. RESULTS: Thirty systematic reviews involving between 157 and 2109 participants (n = 6440 total) were included. Most reviews (n = 28) involved surgical participants. Twenty-five reviews performed meta-analyses. The review quality was commonly rated critically low (n = 22) or low (n = 7). Reviews commonly included combinations of aerobic, resistance and/or respiratory exercise interventions. Pre-operative meta-analyses demonstrated that exercise reduces post-operative complications (n = 4/7) and improves exercise capacity (n = 6/6), whilst HRQoL findings were non-significant (n = 3/3). Post-operative meta-analyses reported significant improvements in exercise capacity (n = 2/3) and muscle strength (n = 1/1) and non-significant HRQoL changes (n = 8/10). Interventions delivered to mixed surgical and non-surgical populations improved exercise capacity (n = 3/4), muscle strength (n = 2/2) and HRQoL (n = 3). Meta-analyses of interventions in non-surgical populations demonstrated inconsistent findings. Adverse event rates were low, however, few reviews reported on safety. CONCLUSIONS: A large body of evidence supports lung cancer exercise interventions to reduce complications and improve exercise capacity in pre- and post-operative populations. Additional higher-quality research is needed, particularly in the non-surgical population, including subgroup analyses of exercise type and setting.

6.
PM R ; 15(1): 31-40, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35138036

RESUMO

INTRODUCTION: Exercise testing is essential to determine the safety and efficacy of prescribing exercise. Limited evidence exists to support remotely supervised exercise testing in oncology literature. OBJECTIVE: To determine the feasibility, safety, and convergent validity of the 30-second sit-to-stand test (30STS) delivered via telehealth in an oncology population. Exploratory analyses informed remote test feasibility according to participant and treatment characteristics. DESIGN: Cross-sectional, observational study. SETTING: Telehealth outpatient clinic, tertiary metropolitan oncology hospital. PARTICIPANTS: Thirty-two consecutive outpatients attending telehealth exercise appointments were screened for inclusion. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A pre-test safety screening questionnaire included the Australia-modified Karnofsky Performance Status (AKPS) and Clinical Frailty Scale (CFS). Following one practice, one 30STS test was completed using a standardized protocol modified for telehealth assessment. Secondary measures: International Physical Activity Questionnaire-Short Form (IPAQ-SF) and pre/post-test Borg Rating of Perceived Exertion (RPE). RESULTS: Thirty participants were deemed as being safe using the screening questionnaire and completed the remote 30STS. Participants were a median (interquartile range [IQR]) 62.5 (51.8 to 66.5) years old, 59% male, 72% undergoing cancer treatment, 34% with metastatic disease, and 56% met current exercise guidelines. Moderate correlation was found between 30STS and IPAQ-SF (rho = 0.49, p = .006), providing evidence of convergent validity. Correlations between 30STS and AKPS (rho = 0.26, p = .161), and CFS (rho = -0.23, p = .214), were fair. Chair-height standardization was poor (range 43 to 60 cm). The clinician could visualize the participant's whole body in 2 of 30 tests. No significant difference in test performance was found for participants with metastatic disease, higher age, or body mass index. No adverse events occurred. CONCLUSION: With screening, the 30STS, performed by telehealth, is a safe and feasible measure of function and lower limb strength. Telehealth exercise testing presents challenges in standardizing the environment and ensuring participant safety. Minimal space and equipment requirements and moderate convergent validity with physical activity provide good clinical utility in this setting.


Assuntos
Neoplasias , Telemedicina , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Estudos de Viabilidade , Estudos Transversais , Modalidades de Fisioterapia , Neoplasias/diagnóstico , Neoplasias/terapia
7.
AAPS J ; 25(1): 10, 2022 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-36482268

RESUMO

The rapid development of biologics and vaccines in response to the current pandemic has highlighted the need for robust platform assays to characterize diverse biopharmaceuticals. A critical aspect of biopharmaceutical development is achieving a highly pure product, especially with respect to residual host cell material. Specifically, two important host cell impurities of focus within biopharmaceuticals are residual DNA and protein. In this work, a novel high-throughput host cell DNA quantitation assay was developed for rapid screening of complex vaccine drug substance samples. The developed assay utilizes the commercially available, fluorescent-sensitive Picogreen dye within a 96-well plate configuration to allow for a cost effective and rapid analysis. The assay was applied to in-process biopharmaceutical samples with known interferences to the dye, including RNA and protein. An enzymatic digestion pre-treatment was found to overcome these interferences and thus allow this method to be applied to wide-ranging, diverse analyses. In addition, the use of deoxycholate in the digestion treatment allowed for disruption of interactions in a given sample matrix in order to more accurately and selectively quantitate DNA. Critical analytical figures of merit for assay performance, such as precision and spike recovery, were evaluated and successfully demonstrated. This new analytical method can thus be successfully applied to both upstream and downstream process analysis for biologics and vaccines using an innovative and automated high-throughput approach.


Assuntos
Produtos Biológicos , Vacinas , Projetos de Pesquisa , DNA
8.
Anal Chem ; 94(3): 1678-1685, 2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-34928586

RESUMO

The employment of ethylenediaminetetraacetic acid (EDTA) across several fields in chemistry and biology has required the creation of a high number of quantitative assays. Nonetheless, the determination of trace EDTA, especially in biologics and vaccines, remains challenging. Herein, we introduce an automated high-throughput approach based on EDTA esterification in 96-well plates using boron trifluoride-methanol combined with rapid analysis by ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry (UHPLC-QqQ-MS/MS). Derivatization of EDTA to its methyl ester (Me-EDTA) serves to significantly improve chromatographic performance (retention, peak shape, and selectivity), while also delivering a tremendous enhancement of sensitivity in the positive ion mode electrospray ionization (ESI+). This procedure, in contrast to previous EDTA methods based on complexation with metal ions, is not affected by high concentration of other metals, buffers, and related salts abundantly present in biopharmaceutical processes (e.g., iron, copper, citrate, etc.). Validation of this assay for the determination of ng·mL-1 level EDTA in monoclonal antibody and vaccine products demonstrated excellent performance (repeatability, precision, and linear range) with high recovery from small sample volumes while also providing an advantageous automation-friendly workflow for high-throughput analysis.


Assuntos
Produtos Biológicos , Vacinas , Boranos , Cromatografia Líquida de Alta Pressão/métodos , Ácido Edético , Metanol , Espectrometria de Massas em Tandem/métodos
9.
FASEB Bioadv ; 3(10): 855-865, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34632319

RESUMO

The damaging effects of air pollution on the skin are becoming increasingly researched and the outcomes of this research are now a major influence in the selection and development of protective ingredients for skincare formulations. However, extensive research has not yet been conducted into the specific cellular defense systems that are being affected after exposure to such pollutants. Research investigating the affected systems is integral to the development of suitable interventions that are capable of augmenting the systems most impacted by air pollutant exposure. The following studies involved exposing primary human dermal fibroblasts to different concentrations of particulate matter and analyzing its effects on mitochondrial complex activity, nuclear factor erythroid 2-related factor 2 localization using immunocytochemistry and protein expression of electron transport chain complex proteins, sirtuin-1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) using western blotting. Particulate matter-induced alterations in both mitochondrial complex protein and activity, indicating oxidative stress, which was also complimented by increased expression of antioxidant proteins GSTP1/2 and SOD2. Particulate matter also seemed to modify expression of the proteins SIRT1 and PGC-1α which are heavily involved in the regulation of mitochondrial biogenesis and energy metabolism. Given the reported results indicating that particulate matter induces damage through oxidative stress and has a profound effect on mitochondrial homeostasis, interventions involving targeted mitochondrial antioxidants may help to minimize the damaging downstream effects of pollutant-induced oxidative stress originating from the mitochondria.

10.
Methods Mol Biol ; 2277: 345-356, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34080161

RESUMO

Mitochondrial DNA (mtDNA) has been demonstrated to be a reliable biomarker of UV-induced genetic damage in both animal and human skin. Properties of the mitochondrial genome which allow for its use as a biomarker of damage include its presence in multiple copies within a cell, its limited repair mechanisms, and its lack of protective histones. To measure UV-induced mtDNA damage (particularly in the form of strand breaks), real-time quantitative PCR (qPCR) is used, based on the observation that PCR amplification efficiency is decreased in the presence of high levels of damage. Here, we describe the measurement of UV-induced mtDNA damage which includes the extraction of cellular DNA, qPCR to determine the relative amount of mtDNA, qPCR to determine UV-induced damage within a long strand of mtDNA, and the verification of the amplification process using gel electrophoresis.


Assuntos
DNA Mitocondrial/análise , DNA Mitocondrial/efeitos da radiação , Eletroforese em Gel de Ágar/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Pele/efeitos da radiação , Biomarcadores/análise , Dano ao DNA , DNA Mitocondrial/isolamento & purificação , Marcadores Genéticos , Humanos , Raios Ultravioleta/efeitos adversos
11.
Aging Cell ; 19(10): e13248, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32990346

RESUMO

Alterations in metabolism in skin are accelerated by environmental stressors such as solar radiation, leading to premature aging. The impact of aging on mitochondria is of interest given their critical role for metabolic output and the finding that environmental stressors cause lowered energy output, particularly in fibroblasts where damage accumulates. To better understand these metabolic changes with aging, we performed an in-depth profiling of the expression patterns of dermal genes in face, forearm, and buttock biopsies from females of 20-70 years of age that encode for all subunits comprising complexes I-V of the mitochondrial electron transport chain. This complements previous preliminary analyses of these changes. "Oxidative phosphorylation" was the top canonical pathway associated with aging in the face, and genes encoding for numerous subunits had decreased expression patterns with age. Investigations on fibroblasts from older aged donors also showed decreased gene expression of numerous subunits from complexes I-V, oxidative phosphorylation rates, spare respiratory capacity, and mitochondrial number and membrane potential compared to younger cells. Treatment of older fibroblasts with nicotinamide (Nam) restored these measures to younger cell levels. Nam increased complexes I, IV, and V activity and gene expression of representative subunits. Elevated mt-Keima staining suggests a possible mechanism of action for these restorative effects via mitophagy. Nam also improved mitochondrial number and membrane potential in younger fibroblasts. These findings show there are significant changes in mitochondrial functionality with aging and that Nam treatment can restore bioenergetic efficiency and capacity in older fibroblasts with an amplifying effect in younger cells.


Assuntos
Fibroblastos/metabolismo , Mitocôndrias/metabolismo , Niacinamida/metabolismo , Pele/patologia , Adulto , Idoso , Células Cultivadas , Humanos , Pessoa de Meia-Idade , Doadores de Tecidos , Adulto Jovem
12.
Appl Physiol Nutr Metab ; 43(3): 303-306, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29125915

RESUMO

We report that reactive oxygen species (ROS), as measured in capillary blood taken from the finger-tip, increased after a marathon (+128% P < 0.01; effect size = 1.17), indicating that this collection method might be useful for measuring ROS in field settings. However, mitochondrial DNA damage remained unchanged. Beetroot juice, taken before and after exercise, was unable to mitigate exercise-induced ROS production, questioning its use an antioxidant-rich food.


Assuntos
Antioxidantes/farmacologia , Beta vulgaris/química , Sucos de Frutas e Vegetais/análise , Espécies Reativas de Oxigênio/sangue , Adulto , Antioxidantes/química , Dano ao DNA , DNA Mitocondrial/genética , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto
14.
Maturitas ; 93: 34-40, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27215947

RESUMO

Ageing describes the progressive functional decline of an organism over time, leading to an increase in susceptibility to age-related diseases and eventually to death, and it is a phenomenon observed across a wide range of organisms. Despite a vast repertoire of ageing studies performed over the past century, the exact causes of ageing remain unknown. For over 50 years it has been speculated that mitochondria play a key role in the ageing process, due mainly to correlative data showing an increase in mitochondrial dysfunction, mitochondrial DNA (mtDNA) damage, and reactive oxygen species (ROS) with age. However, the exact role of the mitochondria in the ageing process remains unknown. The skin is often used to study human ageing, due to its easy accessibility, and the observation that the ageing process is able to be accelerated in this organ via environmental insults, such as ultra violet radiation (UVR). This provides a useful tool to investigate the mechanisms regulating ageing and, in particular, the role of the mitochondria. Observations from dermatological and photoageing studies can provide useful insights into chronological ageing of the skin and other organs such as the brain and liver. Moreover, a wide range of diseases are associated with ageing; therefore, understanding the cause of the ageing process as well as regulatory mechanisms involved could provide potentially advantageous therapeutic targets for the prevention or treatment of such diseases.


Assuntos
Envelhecimento/metabolismo , DNA Mitocondrial , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Pele/metabolismo , Animais , Humanos
15.
J Invest Dermatol ; 136(5): 912-919, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26829036

RESUMO

The mitochondrial theory of aging remains one of the most widely accepted aging theories and implicates mitochondrial electron transport chain dysfunction with subsequent increasing free radical generation. Recently, complex II of the electron transport chain appears to be more important than previously thought in this process, suggested predominantly by nonhuman studies. We investigated the relationship between complex II and aging using human skin as a model tissue. The rate of complex II activity per unit of mitochondria was determined in fibroblasts and keratinocytes cultured from skin covering a wide age range. Complex II activity significantly decreased with age in fibroblasts (P = 0.015) but not in keratinocytes. This was associated with a significant decline in transcript expression (P = 0.008 and P = 0.001) and protein levels (P = 0.0006 and P = 0.005) of the succinate dehydrogenase complex subunit A and subunit B catalytic subunits of complex II, respectively. In addition, there was a significant decrease in complex II activity with age (P = 0.029) that was specific to senescent skin cells. There was no decrease in complex IV activity with increasing age, suggesting possible locality to complex II.


Assuntos
Complexo II de Transporte de Elétrons/deficiência , Fibroblastos/citologia , Erros Inatos do Metabolismo , Mitocôndrias/genética , Doenças Mitocondriais , Envelhecimento da Pele/genética , Biomarcadores/metabolismo , Células Cultivadas , Feminino , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Masculino , Medição de Risco , Sensibilidade e Especificidade , Envelhecimento da Pele/patologia , Espectrofotometria
16.
Infect Immun ; 83(9): 3675-83, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26150536

RESUMO

The Lyme disease spirochete, Borrelia burgdorferi, expresses RevA and numerous outer surface lipoproteins during mammalian infection. As an adhesin that promotes bacterial interaction with fibronectin, RevA is poised to interact with the extracellular matrix of the host. To further define the role(s) of RevA during mammalian infection, we created a mutant that is unable to produce RevA. The mutant was still infectious to mice, although it was significantly less well able to infect cardiac tissues. Complementation of the mutant with a wild-type revA gene restored heart infectivity to wild-type levels. Additionally, revA mutants led to increased evidence of arthritis, with increased fibrotic collagen deposition in tibiotarsal joints. The mutants also induced increased levels of the chemokine CCL2, a monocyte chemoattractant, in serum, and this increase was abolished in the complemented strain. Therefore, while revA is not absolutely essential for infection, deletion of revA had distinct effects on dissemination, arthritis severity, and host response.


Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Borrelia burgdorferi/patogenicidade , Doença de Lyme/imunologia , Doença de Lyme/patologia , Animais , Proteínas da Membrana Bacteriana Externa/imunologia , Western Blotting , Modelos Animais de Doenças , Feminino , Técnicas de Inativação de Genes , Doença de Lyme/genética , Camundongos
17.
Methods Mol Biol ; 1265: 379-88, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25634289

RESUMO

Mitochondrial DNA (mtDNA) has been demonstrated to be a reliable biomarker of UV-induced genetic damage in both animal and human skin. Properties of the mitochondrial genome which allow for its use as a biomarker of damage include its presence in multiple copies within a cell, its limited repair mechanisms, and its lack of protective histones. To measure UV-induced mtDNA damage (particularly in the form of strand breaks), real-time quantitative PCR (qPCR) is used, based on the observation that PCR amplification efficiency is decreased in the presence of high levels of damage. Here, we describe the measurement of UV-induced mtDNA damage, including the extraction of cellular DNA, qPCR to determine the relative amount of mtDNA, qPCR to determine UV-induced damage within a long strand of mtDNA, and the verification of the amplification process using gel electrophoresis.


Assuntos
Dano ao DNA/efeitos da radiação , DNA Mitocondrial/genética , Mitocôndrias/genética , Mitocôndrias/efeitos da radiação , Pele/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Eletroforese em Gel de Ágar , Humanos , Reação em Cadeia da Polimerase em Tempo Real
19.
Redox Biol ; 2: 1016-22, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25460738

RESUMO

The mitochondrial respiratory chain is a major generator of cellular oxidative stress, thought to be an underlying cause of the carcinogenic and ageing process in many tissues including skin. Previous studies of the relative contributions of the respiratory chain (RC) complexes I, II and III towards production of reactive oxygen species (ROS) have focussed on rat tissues and certainly not on human skin which is surprising as this tissue is regularly exposed to UVA in sunlight, a potent generator of cellular oxidative stress. In a novel approach we have used an array of established specific metabolic inhibitors and DHR123 fluorescence to study the relative roles of the mitochondrial RC complexes in cellular ROS production in 2 types of human skin cells. These include additional enhancement of ROS production by exposure to physiological levels of UVA. The effects within epidermal and dermal derived skin cells are compared to other tissue cell types as well as those harbouring a compromised mitochondrial status (Rho-zero A549). The results show that the complex II inhibitor, TTFA, was the only RC inhibitor to significantly increase UVA-induced ROS production in both skin cell types (P<0.05) suggesting that the role of human skin complex II in terms of influencing ROS production is more important than previously thought particularly in comparison to liver cells. Interestingly, two-fold greater maximal activity of complex II enzyme was observed in both skin cell types compared to liver (P<0.001). The activities of RC enzymes appear to decrease with increasing age and telomere length is correlated with ageing. Our study showed that the level of maximal complex II activity was higher in the MRC5/hTERT (human lung fibroblasts transfected with telomerase) cells than the corresponding wild type cells (P=0.0012) which can be considered (in terms of telomerase activity) as models of younger and older cells respectively.


Assuntos
Complexo II de Transporte de Elétrons/metabolismo , Mitocôndrias/enzimologia , Proteínas Mitocondriais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Pele/enzimologia , Raios Ultravioleta/efeitos adversos , Linhagem Celular , Complexo II de Transporte de Elétrons/genética , Humanos , Mitocôndrias/patologia , Pele/patologia
20.
Sci Rep ; 3: 2386, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23989080

RESUMO

A current threat to the marine ecosystem is the high level of solar ultraviolet radiation (UV). Large whales have recently been shown to suffer sun-induced skin damage from continuous UV exposure. Genotoxic consequences of such exposure remain unknown for these long-lived marine species, as does their capacity to counteract UV-induced insults. We show that UV exposure induces mitochondrial DNA damage in the skin of seasonally sympatric fin, sperm, and blue whales and that this damage accumulates with age. However, counteractive molecular mechanisms are markedly different between species. For example, sperm whales, a species that remains for long periods at the sea surface, activate genotoxic stress pathways in response to UV exposure whereas the paler blue whale relies on increased pigmentation as the season progresses. Our study also shows that whales can modulate their responses to fluctuating levels of UV, and that different evolutionary constraints may have shaped their response strategies.


Assuntos
Dano ao DNA/genética , Dano ao DNA/efeitos da radiação , Pele/fisiopatologia , Pele/efeitos da radiação , Cachalote/fisiologia , Luz Solar/efeitos adversos , Raios Ultravioleta/efeitos adversos , Animais , Proteoma/metabolismo , Especificidade da Espécie
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