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1.
Molecules ; 29(8)2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38675711

RESUMO

Although much less common than anthocyanins, 3-Deoxyanthocyanidins (3-DAs) and their glucosides can be found in cereals such as red sorghum. It is speculated that their bioavailability is higher than that of anthocyanins. Thus far, little is known regarding the therapeutic effects of 3-DAs and their O-ß-D-glucosides on cancer, including prostate cancer. Thus, we evaluated their potential to decrease cell viability, to modulate the activity of transcription factors such as NFκB, CREB, and SOX, and to regulate the expression of the gene CDH1, encoding E-Cadherin. We found that 4',7-dihydroxyflavylium chloride (P7) and the natural apigeninidin can reduce cell viability, whereas 4',7-dihydroxyflavylium chloride (P7) and 4'-hydroxy-7-O-ß-D-glucopyranosyloxyflavylium chloride (P3) increase the activities of NFkB, CREB, and SOX transcription factors, leading to the upregulation of CDH1 promoter activity in PC-3 prostate cancer cells. Thus, these compounds may contribute to the inhibition of the epithelial-to-mesenchymal transition in cancer cells and prevent the metastatic activity of more aggressive forms of androgen-resistant prostate cancer.


Assuntos
Antocianinas , Caderinas , Glucosídeos , Regiões Promotoras Genéticas , Neoplasias da Próstata , Sorghum , Humanos , Masculino , Antocianinas/farmacologia , Antocianinas/química , Antígenos CD/metabolismo , Antígenos CD/genética , Caderinas/efeitos dos fármacos , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glucosídeos/farmacologia , Glucosídeos/química , NF-kappa B/metabolismo , Células PC-3 , Regiões Promotoras Genéticas/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Sorghum/química
2.
Biochem Biophys Res Commun ; 663: 32-40, 2023 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-37119763

RESUMO

Cadherins are transmembrane proteins that mediate cell-to-cell adhesion and various cellular processes. In Sertoli cells of the testis, Cdh2 contributes to the development of the testis and the formation of the blood-testis barrier, being essential for germ cells' protection. Analyses of chromatin accessibility and epigenetic marks in adult mouse testis have shown that the region from -800 to +900 bp respective to Cdh2 transcription start site (TSS) is likely the active regulatory region of this gene. In addition, the JASPAR 2022 matrix has predicted an AP-1 binding element at about -600 bp. Transcription factors of the activator protein 1 (AP-1) family have been implicated in the regulation of the expression of genes encoding cell-to-cell interaction proteins such as Gja1, Nectin2 and Cdh3. To test the potential regulation of Cdh2 by members of the AP-1 family, siRNAs were transfected into TM4 Sertoli cells. The knockdown of Junb led to a decrease in Cdh2 expression. ChIP-qPCR and luciferase reporter assays with site-directed mutagenesis confirmed the recruitment of Junb to several AP-1 regulatory elements in the proximal region of the Cdh2 promoter in TM4 cells. Further investigation with luciferase reporter assays showed that other AP-1 members can also activate the Cdh2 promoter albeit to a lesser extent than Junb. Taken together, these data suggest that in TM4 Sertoli cells, Junb is responsible for the regulation of Cdh2 expression which requires its recruitment to the proximal region of the Cdh2 promoter.


Assuntos
Células de Sertoli , Fator de Transcrição AP-1 , Camundongos , Masculino , Animais , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Células de Sertoli/metabolismo , Testículo/metabolismo , Caderinas/genética , Caderinas/metabolismo , Luciferases/metabolismo , Fatores de Transcrição/metabolismo
3.
Mol Reprod Dev ; 90(1): 27-41, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36468795

RESUMO

In Sertoli cells of the testis, cadherins (Cdh) are important cell-to-cell interaction proteins and contribute to the formation of the blood-testis barrier being essential for germ cells' protection. P-cadherin or Cdh3 is only expressed in Sertoli cells from embryonic to prepubertal development. Interestingly, the expression profile of Cdh3 correlates with that of activating protein-1 (AP-1) transcription factors during Sertoli cells development. To assess their potential implications in the regulation of Cdh3, different AP-1 transcription factors were overexpressed in 15P-1 Sertoli cells. We found that the overexpressions of Junb and Fosl2 activated Cdh3 promoter. ChIP-qPCR assay and luciferase reporter assay with 5' promoter deletions and site-directed mutagenesis confirmed the recruitment of Junb and Fosl2 to an AP-1 regulatory element at -47 bp in the proximal region of Cdh3 promoter in 15P-1 cells. These findings were further supported by histone modification markers and chromatin accessibility surrounding Cdh3 promoter in mouse testis. Moreover, the knockdowns of Junb and/or Fosl2 by siRNA decreased Cdh3 protein levels. Taken together, these data suggest that in 15P-1 Sertoli cells, the AP-1 family members Junb and Fosl2 are responsible for the regulation of Cdh3 expression, which requires the recruitment of both factors to the proximal region of the Cdh3 promoter.


Assuntos
Células de Sertoli , Fator de Transcrição AP-1 , Animais , Masculino , Camundongos , Caderinas/genética , Caderinas/metabolismo , Regiões Promotoras Genéticas , Células de Sertoli/metabolismo , Testículo/metabolismo , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Fatores de Transcrição/genética
4.
Mol Cell Biochem ; 478(4): 791-805, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36094721

RESUMO

Connexin 43 (Cx43, also known as Gja1) is the most abundant testicular gap junction protein. It has a crucial role in the support of spermatogenesis by Sertoli cells in the seminiferous tubules as well as in androgen synthesis by Leydig cells. The multifunctional family of Ca2+/calmodulin-dependent protein kinases (CaMK) is composed of CaMK I, II, and IV and each can serve as a mediator of nuclear Ca2+ signals. These kinases can control gene expression by phosphorylation of key regulatory sites on transcription factors. Among these, AP-1 members cFos and cJun are interesting candidates that seem to cooperate with CaMKs to regulate Cx43 expression in Leydig cells. In this study, the Cx43 promoter region important for CaMK-dependent activation is characterized using co-transfection of plasmid reporter-constructs with different plasmids coding for CaMKs and/or AP-1 members in MA-10 Leydig cells. Here we report that the activation of Cx43 expression by cFos and cJun is increased by CaMKI. Furthermore, results from chromatin immunoprecipitation suggest that the recruitment of AP-1 family members to the proximal region of the Cx43 promoter may involve another uncharacterized AP-1 DNA regulatory element and/or protein-protein interactions with other partners. Thus, our data provide new insights into the molecular regulatory mechanisms that control mouse Cx43 transcription in testicular Leydig cells.


Assuntos
Células Intersticiais do Testículo , Neoplasias , Masculino , Camundongos , Animais , Células Intersticiais do Testículo/metabolismo , Conexina 43/genética , Conexina 43/metabolismo , Proteína Quinase Tipo 1 Dependente de Cálcio-Calmodulina/metabolismo , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Neoplasias/metabolismo
5.
Reprod Fertil Dev ; 35(14): 641-660, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37717581

RESUMO

Cadherins (CDH) are crucial intercellular adhesion molecules, contributing to morphogenesis and creating tissue barriers by regulating cells' movement, clustering and differentiation. In the testis, classical cadherins such as CDH1, CDH2 and CDH3 are critical to gonadogenesis by promoting the migration and the subsequent clustering of primordial germ cells with somatic cells. While CDH2 is present in both Sertoli and germ cells in rodents, CDH1 is primarily detected in undifferentiated spermatogonia. As for CDH3, its expression is mainly found in germ and pre-Sertoli cells in developing gonads until the establishment of the blood-testis barrier (BTB). This barrier is made of Sertoli cells forming intercellular junctional complexes. The restructuring of the BTB allows the movement of early spermatocytes toward the apical compartment as they differentiate during a process called spermatogenesis. CDH2 is among many junctional proteins participating in this process and is regulated by several pathways. While cytokines promote the disassembly of the BTB by enhancing junctional protein endocytosis for degradation, testosterone facilitates the assembly of the BTB by increasing the recycling of endocytosed junctional proteins. Mitogen-activated protein kinases (MAPKs) are also mediators of the BTB kinetics in many chemically induced damages in the testis. In addition to regulating Sertoli cell functions, follicle stimulating hormone can also regulate the expression of CDH2. In this review, we discuss the current knowledge on regulatory mechanisms of cadherin localisation and expression in the testis.


Assuntos
Caderinas , Testículo , Masculino , Animais , Testículo/metabolismo , Caderinas/metabolismo , Células de Sertoli/metabolismo , Espermatogênese , Espermatócitos/metabolismo
6.
J Interprof Care ; 37(3): 504-514, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35543316

RESUMO

Despite the importance of teamwork in the operating room (OR), teamwork can often be conflated with teamwork components (e.g., communication, cooperation). We reviewed the existing literature pertaining to OR teamwork to understand which teamwork components have been assessed. Following PRISMA guidelines for scoping reviews, 4,233 peer-reviewed studies were identified using MEDLINE and Embase. Eighty-seven studies were included for synthesis and analysis. Using the episodic model of teamwork as an organizing framework, studies were grouped into the following teamwork categories: (a) transition processes (e.g., goal specification), (b) action processes (e.g., coordination), (c) interpersonal processes (e.g., conflict management), (d) emergent states (e.g., psychological safety), or (e) omnibus topics (a combination of higher-order teamwork processes). Results demonstrated that action processes were most frequently explored, followed by transition processes, omnibus topics, emergent states, and interpersonal processes. Although all studies were framed as investigations of teamwork, it is important to highlight that most explored only one or a few constructs under the overarching umbrella of teamwork. We advocate for enhanced specificity with descriptions of OR teamwork, reporting practices pertaining to interprofessional demographics and outcomes, and increased diversity in study design and surgery type to advance understanding of teamwork and its implications.


Assuntos
Relações Interprofissionais , Salas Cirúrgicas , Humanos , Comunicação , Comportamento Cooperativo , Equipe de Assistência ao Paciente
7.
Int J Mol Sci ; 23(21)2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36361676

RESUMO

Transcription factors members of the basic leucine zipper (bZIP) class play important roles in the regulation of genes and functions in testicular Leydig cells. Many of these factors, such as cAMP responsive element binding protein 1 (CREB1) and CCAAT enhancer binding protein beta (CEBPB), are regulated by the cAMP/protein kinase A (PKA) pathway, the main signaling pathway activated following the activation of the luteinizing hormone/choriogonadotropin membrane receptor LHCGR by the - hormone LH. Others, such as X-box binding protein 1 (XBP1) and members of the cAMP responsive element binding protein 3 (CREB3)-like superfamily, are implicated in the endoplasmic reticulum stress by regulating the unfolded protein response. In this review, the influences of bZIP transcription factors, including CREB1, CEBPB and activator protein 1 (AP-1) family members, on the regulation of genes important for cell proliferation, steroidogenesis and Leydig cell communication will be covered. In addition, unresolved questions regarding the mechanisms of actions of bZIP members in gene regulation will be identified.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica , Células Intersticiais do Testículo , Masculino , Humanos , Células Intersticiais do Testículo/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Regulação da Expressão Gênica , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Zíper de Leucina/genética
8.
Curr Issues Mol Biol ; 44(1): 73-93, 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-35723385

RESUMO

In aging males, androgen production by testicular Leydig cells decreases at a rate of approximately 1% per year. Phenolic compounds may enhance testosterone biosynthesis and delay the onset of male hypogonadism. Gigantol is a bibenzyl compound isolated from several types of orchids of the genus Dendrobium. This compound has various biological activities, including antioxidant activity. However, its capacity to regulate gene expression and steroid production in testicular Leydig cells has never been evaluated. We investigated the effect of gigantol on MA-10 Leydig cells' gene expression using an RNA-Seq approach. To further investigate the structure-function relationship of the hydroxy-methoxyphenyl moiety of gigantol, experiments were also performed with ferulic acid and isoferulic acid. According to transcriptomic analysis, all genes coding for cholesterol biosynthesis-related enzymes are increased in response to gigantol treatment, resulting in increased lipid droplets accumulation. Moreover, treatments with 10 µM gigantol increased StAR protein levels and progesterone production from MA-10 Leydig cells. However, neither ferulic acid nor isoferulic acid influenced StAR protein synthesis and progesterone production in MA-10 Leydig cells. Thus, our findings indicate that gigantol improves cholesterol and steroid biosynthesis within testicular Leydig cells.

9.
Andrologia ; 53(2): e13960, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33400304

RESUMO

Leydig cell tumours represent 1%-3% of all cases of testicular tumours in men. Such tumours respond poorly to radiation or chemotherapy, including bleomycin-etoposide-cisplatin (BEP) combinatorial therapy. In this study, we investigated an alternative approach involving luteolin to improve the efficacy of chemotherapy. LC540 tumour Leydig cells were treated with BEP (bleomycin 40 µg/ml, etoposide 4 µg/ml, cisplatin 8 µg/ml) and/or luteolin 10 µM for comparison with DMSO-treated cells. We performed a transcriptome analysis using RNA-Seq to characterise changes in biological processes and signalling pathways. Treatments of LC540 tumour Leydig cells with luteolin significantly decreased the expression of genes involved in cholesterol biosynthesis, while increasing the expression of genes related to glutathione conjugation (p < .05). Genes being significantly upregulated in response to BEP treatment were involved in the response to toxic substances and transcriptional regulation. Oppositely, genes being significantly downregulated by BEP treatment were enriched for intracellular signal transduction, cell migration, cell adhesion, reproductive system development and cholesterol biosynthesis. BEP chemotherapy proved to be effective in increasing gene expression related to apoptosis of tumour Leydig cells. However, addition of luteolin to BEP treatment had no other effects on biological processes or pathways related to cancer treatment.


Assuntos
Cisplatino , Neoplasias Testiculares , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Bleomicina/farmacologia , Bleomicina/uso terapêutico , Cisplatino/farmacologia , Etoposídeo/farmacologia , Etoposídeo/uso terapêutico , Humanos , Células Intersticiais do Testículo , Luteolina/farmacologia , Luteolina/uso terapêutico , Masculino , Ratos , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/genética , Transcriptoma
10.
J Sport Exerc Psychol ; 43(3): 248-258, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33952704

RESUMO

The authors explored how sport structure predisposed a team to subgroup formation and influenced athlete interactions and team functioning. A season-long qualitative case study was undertaken with a nationally ranked Canadian track and field team. Semistructured interviews were conducted with coaches (n = 4) and athletes (n = 11) from different event groups (e.g., sprinters, jumpers) at the beginning and at the end of the season. The results highlighted constraints that directly impacted athlete interactions and predisposed the group to subgroup formation (e.g., sport/event type, facility/schedule limitations, team size/change over time). The constraints led to structural divides that impacted interactions but could be overcome through team building, engaging with leaders, and prioritizing communication. These findings underline how structure imposed by the design of sports impacts teammate interactions and how practitioners, coaches, and athletes can manage groups when facing such constraints. The authors describe theoretical and practical implications while also proposing potential future directions.


Assuntos
Esportes , Atletas , Canadá , Humanos , Estações do Ano
11.
J Sport Exerc Psychol ; 43(6): 441-449, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702789

RESUMO

This study used ecological sampling methods to examine associations between youth athletes' experiences receiving and engaging in behaviors indicative of in-group ties, cognitive centrality, and in-group affect (i.e., social identity) during a 3-day competitive ice hockey tournament. Forty-five youth (Mage = 12.39 years; SDage = 1.14 years; 94% male) from nine teams wore an electronically activated recorder that captured brief (50-s) audio observations throughout the tournament. Participants also completed daily diary questionnaires for each day of competition. Multilevel structural equation modeling demonstrated that athletes were more likely to engage in behaviors indicative of in-group affect and cognitive centrality on days when they received as higher-than-average frequency of behaviors indicative of cognitive centrality from teammates, coaches, and parents. The findings suggest that when team members interact in ways that demonstrate they are thinking about their team, they influence fellow members to behave in ways that promote a sense of "us."


Assuntos
Hóquei , Identificação Social , Adolescente , Atletas/psicologia , Feminino , Hóquei/psicologia , Humanos , Masculino , Análise Multinível , Pais
12.
Cell Biol Toxicol ; 36(1): 31-49, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31201582

RESUMO

In males, androgens are mainly produced by Leydig cells from the testis. A critical and highly regulated step of steroidogenesis involves the importation of cholesterol within the mitochondria by the steroidogenic acute regulatory (STAR) protein. During aging, STAR protein levels in Leydig cells gradually decrease, leading to a reduced entry of cholesterol into mitochondria and lower testosterone production. In addition to preserving its steroidogenic capacity, tumor Leydig cells can also be excellent models for evaluating the mechanisms of action of anticancer agents. In this study, we examined whether polyphenolics having structural similarities to luteolin could promote steroidogenic and cancer-related gene expressions within rat L540 tumor Leydig cells. In this cell model, luteolin activated Star expression and increased progesterone as well as testosterone productions. Interestingly, luteolin decreased gene expression related to cholesterol biosynthesis, possibly inhibiting membrane synthesis and cell proliferation. In addition, increased expression of genes such as Fas, Cdkn1a, Atp7b, and Tp53, as well as increased accumulation of cleaved caspase 3 and PARP, in response to luteolin treatment indicates that apoptosis is being activated. Luteolin also modulated the expression of genes involved in stress response, such as glutathione-S transferases Gsta1 and Gstt2, and the unfolded protein response. Thus, dietary luteolin may be effective in Leydig cell tumor chemoprevention and in maintaining steroidogenesis in aging males.


Assuntos
Células Intersticiais do Testículo/metabolismo , Luteolina/metabolismo , Animais , Apoptose/genética , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colesterol/biossíntese , Colesterol/metabolismo , AMP Cíclico/metabolismo , Expressão Gênica/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa Transferase/metabolismo , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/fisiologia , Luteolina/genética , Luteolina/farmacologia , Masculino , Mitocôndrias/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Ratos , Esteroides/biossíntese , Esteroides/metabolismo , Estresse Fisiológico/genética , Estresse Fisiológico/fisiologia , Testosterona/biossíntese , Testosterona/farmacologia
13.
Curr Cardiol Rep ; 22(12): 168, 2020 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-33040200

RESUMO

PURPOSE OF REVIEW: Although rare, sudden cardiac death (SCD) in the young is a tragic event, having a dramatic impact upon all involved. The psychosocial burden associated with SCD can leave friends, families, and entire communities bereft. With only limited evidence to describe the volatile emotional reactions associated with a young SCD, there is an urgent need for care providers to better understand the psychological complexities and impacts faced by both at-risk individuals and those directly affected by these tragic events. RECENT FINDINGS: Current knowledge of the psychosocial implications associated with SCD in the young has recently generated interest in the cardiovascular community, with the goal of addressing prevention strategies (screening), family bereavement, and the psychological impact of at-risk or surviving individuals. With the emergence of novel strategies aimed at reducing the public health impact of SCD in the young, further discussion regarding the psychosocial impact of SCD, encompassing prevention, survivorship, and the downstream communal effects of a young death is required. Support systems and intervention could assist in the management of the associated psychosocial burden, yet there is a lack of clinical guidelines to direct this form of care. There is an important need for multidisciplinary collaboration across subspecialties to provide support to grieving individuals and manage patient well-being throughout the screening process for SCD. This collaborative approach requires the integration of cardiovascular and psychological expertise where relevant.


Assuntos
Morte Súbita Cardíaca , Programas de Rastreamento , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Humanos
14.
Biochem Biophys Res Commun ; 512(4): 678-683, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-30922563

RESUMO

Sertoli cells are localized in seminiferous tubules within the testis. They are the first testicular cells to differentiate during male sex determination. In the adult, Sertoli cells provide nutrients to germ cells, control factors for spermatogenesis and protection by establishing the blood-testis barrier (BTB). This BTB is composed of tight junctions, basal ectoplasmic specializations, adherent junctions and gap junctions. The transcription factor SOX8 is necessary for the maintenance of spermatogenesis during adult life whereas SOX4 is involved in developmental processes. These factors are highly expressed in Sertoli cells. However, few of their target genes in adult Sertoli cells are known. Hence, we compared the transcriptomes of TM4 Sertoli cells overexpressing or not SOX4 or SOX8 using RNA-Seq followed by pathways and networks analyses. We found that SOX4 overexpression leads to downregulated genes enriched for cell junction organization and positive regulation of cell-to-cell adhesion. Upregulated genes in response to SOX8 overexpression were enriched for Sertoli cell development and differentiation. However, downregulated genes were enriched for cell-to-cell adhesion, tight junction interactions, gap junctions' assembly, as well as extracellular matrix binding. Hence, our results confirm that SOX8 is an important mediator of Sertoli cell maturation, whereas SOX4 and SOX8 influence gene expression related to regulation of blood-testis barrier assembly. In addition, TM4 cells can be considered as a useful model to better define the regulatory mechanisms of SOX4 or SOX8 on gene transcription in Sertoli cells.


Assuntos
Fatores de Transcrição SOXC/genética , Fatores de Transcrição SOXE/genética , Células de Sertoli/citologia , Regulação para Cima , Animais , Comunicação Celular , Linhagem Celular , Masculino , Camundongos , Células de Sertoli/metabolismo , Transcriptoma
15.
Mol Reprod Dev ; 85(11): 875-886, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30080944

RESUMO

Within the seminiferous tubules of the testis, Gja1-encoded connexin43 plays a critical role in intercellular communication between Sertoli cells. These cells nurture, protect and stimulate the developing germ cells and spermatids. SOX transcription factors are known to play an important role in male fertility and sex determination; however, their physiological function and the identity of their target genes in postnatal Sertoli cells remain to be defined. Members of the activating protein-1 (AP-1) family have been shown to regulate Gja1 expression in myometrial and testicular cells and to physically interact with SOX members, suggesting that these transcription factors may regulate its expression within the testis. Hence, we performed co-transfections of expression plasmids encoding SOX4, SOX8, SOX9 and cJUN with different mouse Gja1 promoter/luciferase reporter constructs within TM4 and 15P-1 Sertoli cells. We showed that a functional cooperation between cJUN and SOX8 or SOX9 regulates Gja1 expression and may involve DNA regulatory elements located between -132 and -26 bp. Such synergy relies on the recruitment of cJUN to the -47 base pair (bp) AP-1 DNA regulatory element of the mouse Gja1 promoter. Hence, SOX and AP-1 members cooperate to regulate Gja1 within testicular Sertoli cells.


Assuntos
Conexina 43/metabolismo , Regulação da Expressão Gênica , Proteínas Proto-Oncogênicas c-jun/metabolismo , Fatores de Transcrição SOX9/metabolismo , Fatores de Transcrição SOXE/metabolismo , Células de Sertoli/metabolismo , Animais , Linhagem Celular , Conexina 43/genética , Masculino , Camundongos , Proteínas Proto-Oncogênicas c-jun/genética , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOXE/genética , Células de Sertoli/citologia
16.
Mol Cell Biochem ; 447(1-2): 175-187, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29383560

RESUMO

SRY-related box (Sox) transcription factors are conserved among vertebrate species. These proteins regulate multiple processes including sex determination and testis differentiation of the male embryo. Members of the Sox family have been identified in pre- and postnatal testis and are known to play an important role in sex determination (Sry, Sox9), male gonadal development, and fertility (Sox4, Sox8, Sox30). However, their expression profiles per cell types remain elusive. The objectives of this research were to characterize the expression profiles of Sox family members within adult testes using publically available datasets and to determine whether these findings are consistent with literature as well as immunofluorescence and in situ hybridization results. We have found that Sox4, Sox8, Sox9, and Sox12 are highly expressed in Sertoli cells, whereas Sox5, Sox6, and Sox30 were typically expressed in spermatocytes and spermatids. Spermatogonia were characterized by the expressions of Sox3, Sox4, Sox12, Sox13, and Sox18. Hence, these results suggest that Sox transcription factors may play different roles according to cell types of the adult mammalian testis.


Assuntos
Regulação da Expressão Gênica/fisiologia , Fatores de Transcrição SOX/biossíntese , Células de Sertoli/metabolismo , Espermátides/metabolismo , Espermatócitos/metabolismo , Animais , Perfilação da Expressão Gênica , Masculino , Camundongos , Células de Sertoli/citologia , Espermátides/citologia , Espermatócitos/citologia
17.
Cell Biol Toxicol ; 34(1): 23-38, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28455626

RESUMO

Testicular Leydig cells are major contributors of androgen synthesis and secretion, which play an important role in testis development, normal masculinization, maintenance of spermatogenesis, and general male fertility. The rate-limiting step in testosterone biosynthesis involves the transfer of cholesterol to the mitochondrial inner membrane by the steroidogenic acute regulatory (Star) protein, a critical factor in steroid hormone biosynthesis. Once inside the mitochondria, cholesterol is metabolized by the steroidogenic enzyme Cyp11a1 to pregnenolone, which is further converted to testosterone by the action of other steroidogenic enzymes. Interestingly, the Star protein level declines during Leydig cell aging, resulting in defective mitochondrial cholesterol transfer and lower testosterone production. It is possible to delay the age-related decline in testosterone production by increasing Star and/or Cyp11a1 gene expression using supplementation with flavonoids, a group of polyphenolic compounds widely distributed in fruits and vegetables. In this study, we examined whether the distribution of hydroxyl groups among flavones could influence their potency to stimulate steroidogenesis within Leydig cells. Low levels of apigenin, luteolin, chrysin, and baicalein (10 µM) stimulated cAMP-dependent Star, Cyp11a1, and Fdx1 promoters' activation and may increase steroidogenesis within Leydig cells. Indeed, luteolin effectively increased cAMP-dependent accumulation of progesterone from MA-10 Leydig cells, possibly through activation of Star and Fdx1 transcription. Thus, dietary luteolin could be potentially effective to maintain steroid production within aging males.


Assuntos
AMP Cíclico/metabolismo , Flavonas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Esteroides/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Células Intersticiais do Testículo/efeitos dos fármacos , Masculino , Camundongos , Modelos Biológicos , Regiões Promotoras Genéticas
18.
BMC Public Health ; 18(Suppl 2): 1038, 2018 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-30285681

RESUMO

BACKGROUND: Physical literacy is a complex construct influenced by a range of physical, behavioural, affective, and cognitive factors. Researchers are interested in relationships among these constituent factors. The purpose of this study was to investigate how age, gender, and physical competence components of physical literacy relate to a child's adequacy in and predilection for physical activity. METHODS: A sample of 8530 Canadian youth (50% girl) aged 8.0 to 12.9 years participated in the study. Participants completed the Canadian Assessment of Physical Literacy (CAPL) protocol, which assesses physical literacy in four domains: Physical Competence, Daily Behaviour, Motivation and Confidence, and Knowledge and Understanding. Stepwise multiple regression analyses were conducted to investigate the relationship between physical competence components of physical literacy (Progressive Aerobic Cardiovascular Endurance Run [PACER], Canadian Agility and Movement Skill Assessment [CAMSA], sit and reach, handgrip, plank, and body mass index) and children's perceived adequacy and predilection toward physical activity as measured by subscales from the Children's Self-Perceptions of Adequacy in and Predilection for Physical Activity scale (CSAPPA). RESULTS: The variable most strongly associated with adequacy and predilection was the PACER shuttle run score. The PACER accounted for 10.9% of the variance in adequacy and 9.9% of the variance in predilection. Participants' age was inversely related to adequacy (ß = - 0.374) and predilection (ß = - 0.621). The combination of other variables related to adequacy brought the total variance explained to 14.7%, while the model for predilection explained a total of 13.7%. CONCLUSIONS: Results indicate an association between cardiorespiratory fitness and measures of physical activity adequacy and predilection. These findings suggest that practitioners should consider the physiological and psychological makeup of the child, and ways to enhance adequacy and predilection among children with limited cardiorespiratory fitness, in order to create the best possible environment for all children to participate in physical activity.


Assuntos
Exercício Físico , Letramento em Saúde/estatística & dados numéricos , Canadá , Aptidão Cardiorrespiratória , Criança , Estudos Transversais , Feminino , Humanos , Masculino
19.
BMC Public Health ; 18(Suppl 2): 1037, 2018 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-30285703

RESUMO

BACKGROUND: Physical literacy is the foundation of a physically active lifestyle. Sedentary behaviour displays deleterious associations with important health indicators in children. However, the association between sedentary behaviour and physical literacy is unknown. The purpose of this study was to identify the aspects of physical literacy that are associated with key modes of sedentary behaviour among Canadian children participating in the RBC-CAPL Learn to Play study. METHODS: A total of 8,307 children aged 8.0-12.9 years were included in the present analysis. Physical literacy was assessed using the Canadian Assessment of Physical Literacy, which measures four domains (Physical Competence, Daily Behaviour, Motivation and Confidence, Knowledge and Understanding). Screen-based sedentary behaviours (TV viewing, computer and video game use), non-screen sedentary behaviours (reading, doing homework, sitting and talking to friends, drawing, etc.) and total sedentary behaviour were assessed via self-report questionnaire. Linear regression models were used to determine significant (p<0.05) correlates of each mode of sedentary behaviour. RESULTS: In comparison to girls, boys reported more screen time (2.7±2.0 vs 2.2±1.8 hours/day, Cohen's d=0.29), and total sedentary behaviour (4.3±2.6 vs 3.9±2.4 hours/day, Cohen's d=0.19), but lower non-screen-based sedentary behaviour (1.6±1.3 vs 1.7±1.3 hours/day, Cohen's d=0.08) (all p< 0.05). Physical Competence (standardized ß's: -0.100 to -0.036, all p<0.05) and Motivation and Confidence (standardized ß's: -0.274 to -0.083, all p<0.05) were negatively associated with all modes of sedentary behaviour in fully adjusted models. Knowledge and Understanding was negatively associated with screen-based modes of sedentary behaviour (standardized ß's: -0.039 to -0.032, all p<0.05), and positively associated with non-screen sedentary behaviour (standardized ß: 0.098, p<0.05). Progressive Aerobic Cardiovascular Endurance Run score and log-transformed plank score were negatively associated with all screen-based modes of sedentary behaviour, while the Canadian Agility and Movement Skill Assessment score was negatively associated with all modes of sedentary behaviour other than TV viewing (all p<0.05). CONCLUSIONS: These results highlight differences in the ways that screen and non-screen sedentary behaviours relate to physical literacy. Public health interventions should continue to target screen-based sedentary behaviours, given their potentially harmful associations with important aspects of physical literacy.


Assuntos
Comportamento Infantil , Exercício Físico , Letramento em Saúde/estatística & dados numéricos , Comportamento Sedentário , Canadá , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Autorrelato
20.
BMC Public Health ; 18(Suppl 2): 1042, 2018 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-30285783

RESUMO

BACKGROUND: Physical literacy is an emerging construct in children's health promotion, and may impact their lifelong physical activity habits. However, recent data reveal that only a small portion of Canadian children are regularly physically active and/or meet sedentary behaviour guidelines. To our knowledge, no study has investigated the association between physical literacy and movement behaviour guidelines. Therefore, the purpose of this study was to examine the relationship between physical literacy scores in Canadian children who meet or do not meet physical activity and sedentary behaviour guidelines. METHODS: Children (n = 2956; 56.6% girls) aged 8-12 years from 10 Canadian cities had their physical literacy levels measured using the Canadian Assessment of Physical Literacy, which consists of four domains (Physical Competence; Daily Behaviour; Knowledge and Understanding; and Motivation and Confidence) that are aggregated to provide a composite physical literacy score. Physical activity levels were measured by pedometers, and sedentary behaviour was assessed through self-report questionnaire. Analyses were conducted separately for each guideline, comparing participants meeting versus those not meeting the guidelines. Comparisons were performed using MANOVA and logistic regression to control for age, gender, and seasonality. RESULTS: Participants meeting physical activity guidelines or sedentary behaviour guidelines had higher physical literacy domain scores for Physical Competence and for Motivation and Confidence compared to those not meeting either guideline (both p < 0.0001). Participants had increased odds of meeting physical activity guidelines and sedentary behaviour guidelines if they met the minimum recommended level of the Physical Competence and Motivation and Confidence domains. Significant age (OR 0.9; 95% CI: 0.8, 0.9), gender (OR 0.4; 95% CI: 0.3, 0.5) and seasonality effects (OR 1.6; 95% CI: 1.2, 2.2 spring and OR 1.7; 95% CI: 1.2, 2.5 summer, reference winter) were seen for physical activity guidelines, and age (OR 0.8; 95% CI: 0.7, 0.8) and gender effects (OR 1.7; 95% CI: 1.4, 2.0) for sedentary behaviour guidelines. Knowledge and Understanding of physical activity principles was not related to guideline adherence in either model. CONCLUSIONS: These cross-sectional findings demonstrate important associations between physical literacy and guideline adherence for physical activity and sedentary behaviour. Future research should explore the causality of these associations.


Assuntos
Exercício Físico , Fidelidade a Diretrizes/estatística & dados numéricos , Letramento em Saúde/estatística & dados numéricos , Canadá , Criança , Estudos Transversais , Feminino , Guias como Assunto , Humanos , Masculino , Comportamento Sedentário
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