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1.
Antonie Van Leeuwenhoek ; 116(8): 773-789, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37222845

RESUMO

UPS1/YLR193C of Saccharomyces cerevisiae (S. cerevisiae) encodes a mitochondrial intermembrane space protein. A previous study found that Ups1p is needed for normal mitochondrial morphology and that UPS1 deficiency disrupts the intramitochondrial transport of phosphatidic acid in yeast cells and leads to an altered unfolded protein response and mTORC1 signaling activation. In this paper, we first provide evidence showing that the UPS1 gene is involved in the UVC-induced DNA damage response and aging. We show that UPS1 deficiency leads to sensitivity to ultraviolet C (UVC) radiation and that this effect is accompanied by elevated DNA damage, increased intracellular ROS levels, abnormal mitochondrial respiratory function, an increased early apoptosis rate, and shortened replicative lifespan and chronological lifespan. Moreover, we show that overexpression of the DNA damage-induced checkpoint gene RAD9 effectively eliminates the senescence-related defects observed in the UPS1-deficient strain. Collectively, these results suggest a novel role for UPS1 in the UVC-induced DNA damage response and aging.


Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Longevidade , Mitocôndrias/genética , Mitocôndrias/metabolismo , Tolerância a Radiação/genética
2.
Biochem Biophys Res Commun ; 604: 88-95, 2022 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-35303684

RESUMO

Circular RNAs (circRNAs), characterized as single-stranded closed circular RNA molecules, have been established to exert pivotal functions in various biological or pathological processes. Nonetheless, the effects and underlying mechanisms concerning circRNAs on the aging and aging-related diseases remain elusive. We herein compared the expression patterns of circRNAs in young and senescent mouse embryonic fibroblasts (MEFs), and uncovered that circRNF169 was dramatically up-regulated in senescent MEFs compared with that in young MEFs. Therefore, we further digged into the role and potential mechanisms of circRNF169 in the senescence of MEFs. The results of senescence-associate-ß-galactosidase staining and BrdU incorporation assay showed that silencing of circRNF169 significantly delayed MEFs senescence and promoted cell proliferation, while ectopic expression of circRNF169 exhibited the opposite effects. Moreover, the dual-luciferase reporter assay confirmed that circRNF169 acted as an endogenous miR-30c-5p sponge, which accelerated cellular senescence by sequestering and inhibiting miR-30c-5p activity. Taken together, our results suggested that circRNF169 exerted a crucial role in cellular senescence through sponging miR-30c-5p and represented a promising target for aging intervention.


Assuntos
Senescência Celular , MicroRNAs , RNA Circular , Animais , Proliferação de Células/genética , Senescência Celular/genética , Fibroblastos/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/fisiologia , RNA Circular/genética , RNA Circular/fisiologia
3.
Antonie Van Leeuwenhoek ; 112(4): 589-598, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30382435

RESUMO

The Saccharomyces cerevisiae chaperone gene SSB2 belongs to the Hsp70 family. Unlike other HSP70 genes, SSB2 gene expression is reduced after heat shock. It has been reported that Ssb2p can be cross-linked to ribosome-bound nascent polypeptide chains, suggesting a potential role of SSB2 in the endoplasmic reticulum (ER) stress response. In this study, SSB2-deletion and SSB2-overexpression yeast strains were generated and applied to explore the potential mechanism by which SSB2 is involved in the tunicamycin (TM)-induced ER stress response. We demonstrate for the first time that SSB2 deficiency results in reduced resistance to TM, while overexpression of SSB2 increases resistance to TM in an IRE1-HAC1 pathway-dependent manner; these observations are related to changes in intracellular unfolded protein response activities (under the TM-stressed condition). Additionally, SSB2 deletion induces early apoptosis and it may play a causal role in the shortened replicative life span of ssb2Δ mutants observed in this study. These findings highlight the involvement of SSB2 in ER stress responses and ageing in yeast.


Assuntos
Adenosina Trifosfatases/metabolismo , Estresse do Retículo Endoplasmático , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/fisiologia , Adenosina Trifosfatases/genética , Antifúngicos/farmacologia , Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/genética , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Tunicamicina/farmacologia , Resposta a Proteínas não Dobradas/efeitos dos fármacos
4.
Biosci Biotechnol Biochem ; 83(5): 845-850, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30667321

RESUMO

Copper metabolism MURR1 domain-containing 1 (COMMD1) is a protein that participates in multiple cellular processes, including copper homeostasis and nuclear factor kappa B (NF-κB) and hypoxia-inducible factor 1α (HIF-1α) signaling. The COMMD1 upstream regulators X-linked inhibitor of apoptosis protein (XIAP) and p300 and downstream targets such as NF-κB and HIF-1α are involved in the regulation of cell proliferation and cell cycle progression. However, whether COMMD1 regulates cell proliferation and the cell cycle remains unclear. In the present study, we demonstrated that both overexpression and knockdown of COMMD1 affected the proliferation of HEK293 cells, and the cell cycle assay revealed that ectopic expression of COMMD1 arrested the cell cycle at the G1 phase. Furthermore, western blot analysis showed that COMMD1 affected p21 Cip1 levels. Taken together, these results suggest that COMMD1 regulates cell proliferation and cell cycle progression by modulating p21 Cip1 levels. Abbreviations COMMD1: Copper metabolism MURR1 domain containing 1; XIAP: X chromosome-linked inhibitor of apoptosis protein; FCS: Fetal calf serum; WCE: Whole cell extracts; RT-PCR: Reverse transcription-polymerase chain reaction; HEK293: Human embryonic kidney 293; ShRNA: Short hairpin RNA; NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B cells; ARF: Alternate reading frame protein product of the CDKN2A locus.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Ciclo Celular/fisiologia , Proliferação de Células/fisiologia , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos
5.
Cell Biol Int ; 42(7): 794-803, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29288588

RESUMO

Dysfunctional adipogenesis such as subcutaneous lipoatrophy is closely related to insulin resistance and metabolic disorders. Although the expression or release of the cytokine interleukin-1α (IL-1α) is known to increase in adipose tissue in response to cell death, cell senescence, aging, or solar radiation, the regulatory role of IL-1α in adipogenesis has not been sufficiently investigated. To investigate the problem, we explored the effect of IL-1α on the proliferation and adipogenic differentiation of human adipose-derived mesenchymal stem cells (ADSCs) using cell counting, alamarBlue assay, oil red O staining, Western blot, among others. The results showed that IL-1α evidently inhibited the proliferation and adipogenic differentiation of ADSCs, which might be related with the activated nuclear factor-κB (NF-κB) and extracellular signal-regulated kinase (ERK) 1/2 pathways. Early-stage adipogenic differentiation was more sensitive to IL-1α than late-stage differentiation. After differentiation of ADSCs into mature adipocytes, adding of IL-1α had no obvious influence on the cellular morphology, including lipid droplet accumulation. IL-1α enhanced the expression of proinflammatory cytokines, such as IL-8, IL-6, CCL2 (C-C motif chemokine ligand 2), and IL-1ß, when added into the adipogenic medium of ADSCs. Blocking IL-8 and IL-6 with neutralizing antibodies partially alleviated the inhibitory effect of IL-1α on the proliferation and adipogenic differentiation. The results suggest that IL-1α inhibits adipogenesis through activation of NF-κB and ERK1/2 pathways and subsequent upregulation of proinflammatory cytokines in ADSCs. IL-1α might play an important role in mediating lipoatrophy by regulation of ADSCs.


Assuntos
Adipogenia/fisiologia , Interleucina-1alfa/metabolismo , Células-Tronco Mesenquimais/citologia , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , NF-kappa B/metabolismo , Adipócitos/citologia , Tecido Adiposo/citologia , Adulto , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Humanos , Masculino
6.
Luminescence ; 31(3): 813-20, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26387677

RESUMO

To date, several fluorescent probes modified by a single targeting agent have been explored. However, studies on the preparation of dual-function quantum dot (QD) fluorescent probes with dual-targeting action and a therapeutic effect are rare. Here, a dual-targeting CdTe/CdS QD fluorescent probe with a bovine serum albumin-glycyrrhetinic acid conjugate and arginine-glycine-aspartic acid was successfully prepared that could induce the apoptosis of liver cancer cells and showed enhanced targeting in in vitro cell imaging. Therefore, the as-prepared fluorescent probe in this work is an efficient diagnostic tool for the simultaneous detection of liver cancer and breast cancer cells.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Corantes Fluorescentes/farmacologia , Corantes Fluorescentes/uso terapêutico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Animais , Neoplasias da Mama/patologia , Compostos de Cádmio/química , Bovinos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Ácido Glicirretínico/química , Humanos , Neoplasias Hepáticas/patologia , Oligopeptídeos/química , Pontos Quânticos , Soroalbumina Bovina/química , Telúrio/química
7.
FEMS Microbiol Lett ; 3712024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38258560

RESUMO

Autophagy is pivotal in maintaining intracellular homeostasis, which involves various biological processes, including cellular senescence and lifespan modulation. Being an important member of the protein O-mannosyltransferase (PMT) family of enzymes, Pmt1p deficiency can significantly extend the replicative lifespan (RLS) of yeast cells through an endoplasmic reticulum (ER) unfolded protein response (UPR) pathway, which is participated in protein homeostasis. Nevertheless, the mechanisms that Pmt1p regulates the lifespan of yeast cells still need to be explored. In this study, we found that the long-lived PMT1 deficiency strain (pmt1Δ) elevated the expression levels of most autophagy-related genes, the expression levels of total GFP-Atg8 fusion protein and free GFP protein compared with wild-type yeast strain (BY4742). Moreover, the long-lived pmt1Δ strain showed the greater dot-signal accumulation from GFP-Atg8 fusion protein in the vacuole lumen through a confocal microscope. However, deficiency of SAC1 or ATG8, two essential components of the autophagy process, decreased the cell proliferation ability of the long-lived pmt1Δ yeast cells, and prevented the lifespan extension. In addition, our findings demonstrated that overexpression of ATG8 had no potential effect on the RLS of the pmt1Δ yeast cells, and the maintained incubation of minimal synthetic medium lacking nitrogen (SD-N medium as starvation-induced autophagy) inhibited the cell proliferation ability of the pmt1Δ yeast cells with the culture time, and blocked the lifespan extension, especially in the SD-N medium cultured for 15 days. Our results suggest that the long-lived pmt1Δ strain enhances the basal autophagy activity, while deficiency of SAC1 or ATG8 decreases the cell proliferation ability and shortens the RLS of the long-lived pmt1Δ yeast cells. Moreover, the maintained starvation-induced autophagy impairs extension of the long-lived pmt1Δ yeast cells, and even leads to the cell death.


Assuntos
Família da Proteína 8 Relacionada à Autofagia , Monoéster Fosfórico Hidrolases , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Autofagia/genética , Família da Proteína 8 Relacionada à Autofagia/genética , Morte Celular , Proliferação de Células/genética , Monoéster Fosfórico Hidrolases/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética
8.
J Environ Public Health ; 2022: 8717072, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36124249

RESUMO

This study aims to make public sports health emergency corpus as a way to deal with public health emergency such as COVID-19, reducing the losses affected by an illness or health condition that has occurred frequently in recent years. On this basis, this paper analyzes the research status of emergency language services at home and abroad, discusses the significance and principles of Multimodal Aligned Corpus Public Health Emergency (shorted for MACPHE) construction, and develops technical processing paths and building procedures for MACPHE. Finally, it was emphasized that the construction of MACPHE and emergency language resources are important parts of the national language service capacity. Furthermore, on the basis of big data, a modal architecture of MACPHE was given and analyzed in the field of public health service.


Assuntos
COVID-19 , Esportes , Big Data , COVID-19/epidemiologia , Humanos , Saúde Pública
9.
Biomed Res Int ; 2020: 3858465, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32104690

RESUMO

The cytosolic isozyme of phosphoenolpyruvate carboxykinase (PCK1) was the first rate-limiting enzyme in the gluconeogenesis pathway, which exerted a critical role in maintaining the blood glucose levels. PCK1 has been established to be involved in various physiological and pathological processes, including glucose metabolism, lipid metabolism, diabetes, and tumorigenesis. Nonetheless, the association of PCK1 with aging process and the detailed underlying mechanisms of PCK1 on aging are still far to be elucidated. Hence, we herein constructed the PCK1-deficient (pck1Δ) and PCK1 overexpression (PCK1 OE) Saccharomyces cerevisiae. The results unveiled that PCK1 deficiency significantly shortened the replicative lifespan (RLS) in the S. cerevisiae, while overexpression of PCK1 prolonged the RLS. Additionally, we noted that the ROS level was significantly enhanced in PCK1-deficient strain and decreased in PCK1 OE strain. Then, a high throughput analysis by deep sequencing was performed in the pck1Δ and wild-type strains, in an attempt to shed light on the effect of PCK1 on the lifespan of aging process. The data showed that the most downregulated mRNAs were enriched in the regulatory pathways of glucose metabolism. Fascinatingly, among the differentially expressed mRNAs, PFK1 was one of the most upregulated genes, which was involved in the glycolysis process and ROS generation. Thus, we further constructed the pfk1Δpck1Δ strain by deletion of PFK1 in the PCK1-deficient strain. The results unraveled that pfk1Δpck1Δ strain significantly suppressed the ROS level and restored the RLS of pck1Δ strain. Taken together, our data suggested that PCK1 deficiency enhanced the ROS level and shortened the RLS of S. cerevisiae via PFK1.


Assuntos
Regulação Enzimológica da Expressão Gênica , Regulação Fúngica da Expressão Gênica , Fosfoenolpiruvato Carboxiquinase (ATP) , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Fosfoenolpiruvato Carboxiquinase (ATP)/deficiência , Fosfoenolpiruvato Carboxiquinase (ATP)/metabolismo , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
10.
Biomed Res Int ; 2019: 1238581, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275960

RESUMO

Beta-1,3-glucanosyltransferase (Gas1p) plays important roles in cell wall biosynthesis and morphogenesis and has been implicated in DNA damage responses and cell cycle regulation in fungi. Yeast Gas1p has also been reported to participate in endoplasmic reticulum (ER) stress responses. However, the precise roles and molecular mechanisms through which Gas1p affects these responses have yet to be elucidated. In this study, we constructed GAS1-deficient (gas1Δ) and GAS1-overexpressing (GAS1 OE) yeast strains and observed that the gas1Δ strain exhibited a decreased proliferation ability and a shorter replicative lifespan (RLS), as well as enhanced activity of the unfolded protein response (UPR) in the absence of stress. However, under the high-tunicamycin-concentration (an ER stress-inducing agent; 1.0 µg/mL) stress, the gas1Δ yeast cells exhibited an increased proliferation ability compared with the wild-type yeast strain. In addition, our findings demonstrated that IRE1 and HAC1 (two upstream modulators of the UPR) are required for the survival of gas1Δ yeast cells under the tunicamycin stress. On the other hand, we provided evidence that the GAS1 overexpression caused an obvious sensitivity to the low-tunicamycin-concentration (0.25 µg/mL). Collectively, our results indicate that Gas1p plays an important role in the ageing and ER stress responses in yeast.


Assuntos
Glicoproteínas de Membrana/deficiência , Saccharomyces cerevisiae/metabolismo , Resposta a Proteínas não Dobradas , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Replicação do DNA/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Glicoproteínas de Membrana/metabolismo , Viabilidade Microbiana/efeitos dos fármacos , Proteínas Repressoras/metabolismo , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/crescimento & desenvolvimento , Proteínas de Saccharomyces cerevisiae/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tunicamicina/farmacologia , Resposta a Proteínas não Dobradas/efeitos dos fármacos
11.
Mol Med Rep ; 20(2): 1790-1796, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31257505

RESUMO

Lamin A, which is encoded by the LMNA gene, regulates gene expression and genome stability through interactions with a variety of proteins. Mutations in LMNA lead to a diverse set of inherited human diseases, collectively referred to as laminopathies. To gain insight into the protein interactions of lamin A, a yeast two­hybrid screen was conducted using the carboxy­terminus of lamin A. The screen identified copper metabolism MURR1 domain­containing 1 (COMMD1) as a novel lamin A binding partner. Colocalization experiments using fluorescent confocal microscopy revealed that COMMD1 colocalized with lamin A in 293 cells. Furthermore, the COMMD1­lamin A protein interaction was also demonstrated in co­immunoprecipitation experiments. Collectively, the present study demonstrated a physical interaction between COMMD1 and lamin A, which may aid to elucidate the mechanisms of lamin A in the aging process.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Lamina Tipo A/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/análise , Linhagem Celular , Humanos , Lamina Tipo A/análise , Ligação Proteica , Mapas de Interação de Proteínas , Técnicas do Sistema de Duplo-Híbrido
12.
Cell Stress Chaperones ; 23(4): 527-537, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29116578

RESUMO

Ubiquitin is a 76-amino acid protein that is highly conserved among higher and lower eukaryotes. The polyubiquitin gene UBI4 encodes a unique precursor protein that contains five ubiquitin repeats organized in a head-to-tail arrangement. Although the involvement of the yeast polyubiquitin gene UBI4 in the stress response was reported long ago, there are no reports regarding the underlying mechanism of this involvement. In this study, we used UBI4-deletion and UBI4-overexpressing yeast strains as models to explore the potential mechanism by which UBI4 protects yeast cells against paraquat-induced oxidative stress. Here, we show that ubi4Δ cells exhibit oxidative stress, an apoptotic phenotype, and a decreased replicative lifespan. Additionally, the reduced resistance of ubi4Δ cells to paraquat that was observed in this study was rescued by overexpression of either the catalase or the mitochondrial superoxide dismutase SOD2. We also demonstrated that only SOD2 overexpression restored the replicative lifespan of ubi4Δ cells. In contrast to the case of ubi4Δ cells, UBI4 overexpression in wild-type yeast increases the yeast's resistance to paraquat, and this overexpression is associated with large pools of expressed ubiquitin and increased levels of ubiquitinated proteins. Collectively, these findings highlight the role of the polyubiquitin gene UBI4 in apoptosis and implicate UBI4 as a modulator of the replicative lifespan.


Assuntos
Apoptose/genética , Replicação do DNA/genética , Poliubiquitina/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/genética , Ubiquitina C/deficiência , Ubiquitina C/genética , Apoptose/efeitos dos fármacos , Catalase/metabolismo , Replicação do DNA/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mutação/genética , Paraquat/toxicidade , Fenótipo , Espécies Reativas de Oxigênio/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/crescimento & desenvolvimento , Proteínas de Saccharomyces cerevisiae/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Ubiquitina C/metabolismo , Ubiquitinação/efeitos dos fármacos
13.
Cell Death Dis ; 9(3): 260, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29449532

RESUMO

Although targeted therapy and immunotherapy greatly improve the outcome of melanoma, drug resistance and low response rates still maintain the unsubstitutability of traditional chemotherapy. Cisplatin (CDDP) is widely used in different types of tumours with high response rates, but it generally has low efficiency in melanoma. The mechanisms underpinning the phenomena are not sufficiently understood. Here we demonstrated that various melanoma cell lines adopted senescence phenotype after CDDP treatment in contrast to the other types of tumour cells. CDDP treatment induced melanoma A375 cells into senescence through the sequential activation of the DNA damage response and the P53/P21 pathway. All the senescent melanoma cells induced by CDDP alone or the combination of CDDP and dacarbazine developed robust senescence-associated secretory phenotype (SASP), that is, the secretion of multiple cytokines. IL-1α was an early component and an upstream regulator of SASP. Similarly, CDDP either alone or combined with dacarbazine could induce melanoma cell senescence and SASP in either A375 or B16F10 melanoma xenograft mice. The supernatant of senescent A375 cells promoted the growth of normal non-senescent A375 cells and enhanced their expression and secretion of IL-8 through the activation of the ERK1/2-RSK1 pathway. The transplantation of non-senescent and senescent A375 cells together into nude mice showed accelerated tumour growth compared with transplanting non-senescent cells alone; no tumours developed when transplanting senescent cells alone. Following CDDP administration in A375-bearing mice, the intratumour injection of neutralisation antibodies targeting the SASP factors IL-1α or IL-8 evidently delayed tumour growth. The results suggest that the CDDP-induced senescent melanoma cells promote non-senescent cells proliferation through the activation of ERK1/2-RSK1 pathway by the SASP factors. Cell senescence and concomitant SASP may be the particular mechanisms for melanoma to resist chemotherapeutics.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Melanoma/tratamento farmacológico , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Neoplasias Cutâneas/tratamento farmacológico , Células A549 , Animais , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Dacarbazina/farmacologia , Células HeLa , Humanos , Interleucina-1alfa/metabolismo , Melanoma/enzimologia , Melanoma/patologia , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/enzimologia , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Via Secretória , Transdução de Sinais , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/patologia , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
FEMS Microbiol Lett ; 365(21)2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30265296

RESUMO

Protein O-mannosyltransferase-1 (Pmt1p) deficiency extends the replicative lifespan (RLS) of Saccharomyces cerevisiae, which is related to the activation of the unfolded protein response (UPR), an important pathway for alleviating endoplasmic reticulum (ER) stress. Trafficking of Emp24p/Erv25p-dependent cargo disrupted 1 (Ted1p) has been reported as a binding partner of yeast Pmt1p. We explored the potential relationship between Pmt1p and Ted1p in the cell lifespan and ER stress responses. The TED1-deleted strain (ted1Δ) had a shorter RLS with no increase in UPR activity. However, PMT1 deficiency prolonged the short lifespan of ted1Δ in a manner dependent on Hac1p, an upstream transcription factor of the UPR pathway. In addition, PMT1 deficiency enhanced the UPR activity and alleviated the ER stress resistance of the ted1Δ strain. Thus, the enhanced UPR activity was hypothesized to explain the longevity of the pmt1Δted1Δ strain, but this long-lived pmt1Δted1Δ strain showed decreased ER stress resistance compared with the short-lived ted1Δ strain. Taken together, our results suggest a possible relationship between PMT1 and TED1 regarding lifespan regulation and the ER stress response.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Replicação do DNA , Estresse do Retículo Endoplasmático , Manosiltransferases/genética , Proteínas Repressoras/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Regulação Fúngica da Expressão Gênica , Manosiltransferases/metabolismo , Dobramento de Proteína , Proteínas Repressoras/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Transdução de Sinais , Resposta a Proteínas não Dobradas
15.
Evol Psychol ; 15(3): 1474704917723912, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28828887

RESUMO

This study aimed to use evolutionary psychology to explain conspicuous consumption's relationship with mating goals among women. We used experiments to show that power moderates conspicuous consumption's relationship with mating goals among women through an underlying relationship with women's social comparison tendencies. In Study 1, the participants read a passage describing a young woman wearing a coat made by a conspicuous brand (vs. an ordinary brand) who aimed to attract a desired man (vs. aiming to guard against potential competitors' attempts to disrupt her established intimate relationship). Participants in the conspicuous-brand condition were more confident that the young woman would succeed in mate attraction and guarding than participants in the ordinary-brand condition, suggesting the participants believed the conspicuous brands facilitated mate attraction and mate guarding more than ordinary brands. Study 2 manipulated the participants' power states and mating goals and measured participants' social comparison tendencies and conspicuous consumption index values. In the mate-guarding condition, high-power participants showed more inclination toward conspicuous consumption than low-power participants. In the mate-attraction condition, low-power participants showed a greater inclination toward conspicuous consumption than did high-power participants. Comparison orientation also mediated power's effect on conspicuous consumption inclination. The evolutionary psychological basis for the above findings is discussed, and suggestions are offered regarding product marketing.


Assuntos
Comportamento do Consumidor , Poder Psicológico , Comportamento Sexual/psicologia , Comportamento Social , Mulheres/psicologia , Adulto , Feminino , Humanos , Adulto Jovem
16.
Biomed Res Int ; 2017: 7587395, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28828388

RESUMO

Yeast MET18, a subunit of the cytosolic iron-sulfur (Fe/S) protein assembly (CIA) machinery which is responsible for the maturation of Fe/S proteins, has been reported to participate in the oxidative stress response. However, the underlying molecular mechanisms remain unclear. In this study, we constructed a MET18/met18Δ heterozygous mutant yeast strain and found that MET18 deficiency in yeast cells impaired oxidative stress resistance as evidenced by increased sensitivity to hydrogen peroxide (H2O2) and cumene hydroperoxide (CHP). Mechanistically, the mRNA levels of catalase A (CTA1) and catalase T (CTT1) as well as the total catalase activity were significantly reduced in MET18-deficient cells. In contrast, overexpression of CTT1 or CTA1 in MET18-deficient cells significantly increased the intracellular catalase activity and enhanced the resistance ability against H2O2 and CHP. In addition, MET18 deficiency diminished the replicative capacity of yeast cells as evidenced by the shortened replicative lifespan, which can be restored by CTT1 overexpression, but not by CTA1, in the MET18-deficient cells. These results suggest that MET18, in a catalase-dependent manner, plays an essential role in enhancing the resistance of yeast cells to oxidative stress and increasing the replicative capacity of yeast cells.


Assuntos
Envelhecimento/genética , Catalase/genética , Estresse Oxidativo/genética , Proteínas de Saccharomyces cerevisiae/genética , Fatores de Transcrição/genética , Envelhecimento/fisiologia , Derivados de Benzeno/toxicidade , Citosol/metabolismo , Peróxido de Hidrogênio/toxicidade , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Fatores de Transcrição/deficiência
17.
Mech Ageing Dev ; 164: 27-36, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28347693

RESUMO

Ksplp is a nuclear-localized Ser/Thr kinase that is not essential for the vegetative growth of yeast. A global gene function analysis in yeast suggested that Ksplp was involved in the oxidative stress response; however, the underlying mechanism remains unclear. Here, we showed that KSP1-deficient yeast cells exhibit hypersensitivity to the DNA alkylating agent methyl methanesulphonate (MMS), and treatment of the KSP1-deficient strain with MMS could trigger abnormal mitochondrial membrane potential and up-regulate reactive oxygen species (ROS) production. In addition, the mRNA expression level of the catalase gene CTT1 (which encodes cytosolic catalase) and total catalase activity were strongly down-regulated in the KSP1-deleted strain compared with those in wild-type cells. Moreover, the KSP1 deficiency also leads to a shortened replicative lifespan, which could be restored by the increased expression of CTT1. On the other hand, KSP1-overexpressed (KSP1OX) yeast cells exhibited increased resistance towards MMS, an effect that was, at least in part, CTT1 independent. Collectively, these findings highlight the involvement of Ksplp in the DNA damage response and implicate Ksplp as a modulator of the replicative lifespan.


Assuntos
Catalase/biossíntese , Regulação Enzimológica da Expressão Gênica , Regulação Fúngica da Expressão Gênica , Proteínas Serina-Treonina Quinases/deficiência , Espécies Reativas de Oxigênio/metabolismo , Saccharomyces cerevisiae , Catalase/genética , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae
19.
Age (Dordr) ; 37(3): 9788, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25936926

RESUMO

Pmt1p is an important member of the protein O-mannosyltransferase (PMT) family of enzymes, which participates in the endoplasmic reticulum (ER) unfolded protein response (UPR), an important pathway for alleviating ER stress. ER stress and the UPR have been implicated in aging and age-related diseases in several organisms; however, a possible role for PMT1 in determining lifespan has not been previously described. In this study, we report that deletion of PMT1 increases replicative lifespan (RLS) in the budding yeast Saccharomyces cerevisiae, while overexpression of PMT1 (PMT1-OX) reduces RLS. Relative to wild-type and PMT1-OX strains, the pmt1Δ strain had enhanced HAC1 mRNA splicing and elevated expression levels of UPR target genes. Furthermore, the increased RLS of the pmt1Δ strain could be completely abolished by deletion of either IRE1 or HAC1, two upstream modulators of the UPR. The double deletion strains pmt1Δhac1Δ and pmt1Δire1Δ also displayed generally reduced transcription of UPR target genes. Collectively, our results suggest that PMT1 deficiency enhances basal activity of the ER UPR and extends the RLS of yeast mother cells through a mechanism that requires both IRE1 and HAC1.


Assuntos
Envelhecimento/genética , Longevidade/genética , Manosiltransferases/genética , Saccharomyces cerevisiae/genética , Resposta a Proteínas não Dobradas , Envelhecimento/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Western Blotting , Estresse do Retículo Endoplasmático , Manosiltransferases/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Reação em Cadeia da Polimerase , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
20.
PLoS One ; 9(8): e105995, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25153992

RESUMO

Chronic infection with Schistosoma japonicum is an important cause of hepatic fibrosis (HF). Human 9q33.3 is one of the most important loci for stress-related diseases. We examined the potential associations of 43 single-nucleotide polymorphisms (SNPs) with S. japonicum infection and HF in epidemic region in China. We identified a SNP (rs10118570 GG in mitogen-activated protein kinase associated protein 1, MAPKAP1) contributes to anti-infection (adjusted OR = 0.35) and anti-fibrogenesis (adjusted RR = 0.44) in the discovery study. Replicative and combined studies showed consistent protective quality for this genotype (replicative: adjusted OR = 0.37 for anti-infection, and adjusted RR = 0.40 for anti-fibrogenesis; Combined: adjusted OR = 0.45 for anti-infection, and adjusted RR = 0.42 for anti-fibrogenesis). Univariate and multivariate analysis in the discovery, replicative and combined studies, suggested that durations (years), splenomegaly, serum ALB and rs10118570 were independent predictors influencing the fibrogenesis. The analysis of gene-gene interaction showed rs10118570 functions independently. We conclude that MAPKAP1 may represent a novel anti-infection and anti-fibrogenesis genomic locus in chronic schistosomiasis japonica. And rs10118570 may be a potential biomarker and target for the treatment of this life-threatening ancient disease.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Predisposição Genética para Doença/genética , Doenças Negligenciadas/genética , Polimorfismo de Nucleotídeo Único/genética , Esquistossomose Japônica/genética , Adulto , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética/métodos , Genótipo , Humanos , Cirrose Hepática/genética , Masculino , Pessoa de Meia-Idade
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