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1.
Cell ; 186(25): 5457-5471.e17, 2023 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-37979582

RESUMO

Extracellular perception of auxin, an essential phytohormone in plants, has been debated for decades. Auxin-binding protein 1 (ABP1) physically interacts with quintessential transmembrane kinases (TMKs) and was proposed to act as an extracellular auxin receptor, but its role was disputed because abp1 knockout mutants lack obvious morphological phenotypes. Here, we identified two new auxin-binding proteins, ABL1 and ABL2, that are localized to the apoplast and directly interact with the extracellular domain of TMKs in an auxin-dependent manner. Furthermore, functionally redundant ABL1 and ABL2 genetically interact with TMKs and exhibit functions that overlap with those of ABP1 as well as being independent of ABP1. Importantly, the extracellular domain of TMK1 itself binds auxin and synergizes with either ABP1 or ABL1 in auxin binding. Thus, our findings discovered auxin receptors ABL1 and ABL2 having functions overlapping with but distinct from ABP1 and acting together with TMKs as co-receptors for extracellular auxin.


Assuntos
Arabidopsis , Ácidos Indolacéticos , Reguladores de Crescimento de Plantas , Ácidos Indolacéticos/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Arabidopsis/química , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo
2.
Nature ; 599(7884): 278-282, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34707287

RESUMO

The phytohormone auxin controls many processes in plants, at least in part through its regulation of cell expansion1. The acid growth hypothesis has been proposed to explain auxin-stimulated cell expansion for five decades, but the mechanism that underlies auxin-induced cell-wall acidification is poorly characterized. Auxin induces the phosphorylation and activation of the plasma membrane H+-ATPase that pumps protons into the apoplast2, yet how auxin activates its phosphorylation remains unclear. Here we show that the transmembrane kinase (TMK) auxin-signalling proteins interact with plasma membrane H+-ATPases, inducing their phosphorylation, and thereby promoting cell-wall acidification and hypocotyl cell elongation in Arabidopsis. Auxin induced interactions between TMKs and H+-ATPases in the plasma membrane within seconds, as well as TMK-dependent phosphorylation of the penultimate threonine residue on the H+-ATPases. Our genetic, biochemical and molecular evidence demonstrates that TMKs directly phosphorylate plasma membrane H+-ATPase and are required for auxin-induced H+-ATPase activation, apoplastic acidification and cell expansion. Thus, our findings reveal a crucial connection between auxin and plasma membrane H+-ATPase activation in regulating apoplastic pH changes and cell expansion through TMK-based cell surface auxin signalling.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Membrana Celular/metabolismo , Parede Celular/metabolismo , Ácidos Indolacéticos/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Ácidos , Arabidopsis/citologia , Arabidopsis/enzimologia , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Membrana Celular/enzimologia , Ativação Enzimática , Concentração de Íons de Hidrogênio , Hipocótilo/enzimologia , Hipocótilo/crescimento & desenvolvimento , Hipocótilo/metabolismo , Proteínas de Membrana/genética , Fosforilação , Reguladores de Crescimento de Plantas/metabolismo , Proteínas Serina-Treonina Quinases/deficiência , Proteínas Serina-Treonina Quinases/genética , ATPases Translocadoras de Prótons/química , ATPases Translocadoras de Prótons/metabolismo , Prótons , Treonina/metabolismo
3.
Proc Natl Acad Sci U S A ; 120(19): e2218503120, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37126711

RESUMO

The plant hormone auxin plays a key role to maintain root stem cell identity which is essential for root development. However, the molecular mechanism by which auxin regulates root distal stem cell (DSC) identity is not well understood. In this study, we revealed that the cell cycle factor DPa is a vital regulator in the maintenance of root DSC identity through multiple auxin signaling cascades. On the one hand, auxin positively regulates the transcription of DPa via AUXIN RESPONSE FACTOR 7 and ARF19. On the other hand, auxin enhances the protein stability of DPa through MITOGEN-ACTIVATED PROTEIN KINASE 3 (MPK3)/MPK6-mediated phosphorylation. Consistently, mutation of the identified three threonine residues (Thr10, Thr25, and Thr227) of DPa to nonphosphorylated form alanine (DPa3A) highly decreased the phosphorylation level of DPa, which decreased its protein stability and affected the maintenance of root DSC identity. Taken together, this study provides insight into the molecular mechanism of how auxin regulates root distal stem cell identity through the dual regulations of DPa at both transcriptional and posttranslational levels.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Divisão Celular , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Raízes de Plantas/metabolismo , Células-Tronco/metabolismo
4.
Cell ; 143(1): 99-110, 2010 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-20887895

RESUMO

Auxin is a multifunctional hormone essential for plant development and pattern formation. A nuclear auxin-signaling system controlling auxin-induced gene expression is well established, but cytoplasmic auxin signaling, as in its coordination of cell polarization, is unexplored. We found a cytoplasmic auxin-signaling mechanism that modulates the interdigitated growth of Arabidopsis leaf epidermal pavement cells (PCs), which develop interdigitated lobes and indentations to form a puzzle-piece shape in a two-dimensional plane. PC interdigitation is compromised in leaves deficient in either auxin biosynthesis or its export mediated by PINFORMED 1 localized at the lobe tip. Auxin coordinately activates two Rho GTPases, ROP2 and ROP6, which promote the formation of complementary lobes and indentations, respectively. Activation of these ROPs by auxin occurs within 30 s and depends on AUXIN-BINDING PROTEIN 1. These findings reveal Rho GTPase-based auxin-signaling mechanisms, which modulate the spatial coordination of cell expansion across a field of cells.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/citologia , Arabidopsis/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Ácidos Indolacéticos/metabolismo , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Transdução de Sinais , Membrana Celular/metabolismo , Forma Celular , Folhas de Planta/citologia , Proteínas de Plantas/metabolismo , Receptores de Superfície Celular/metabolismo
5.
Nature ; 568(7751): 240-243, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30944466

RESUMO

The plant hormone auxin has crucial roles in almost all aspects of plant growth and development. Concentrations of auxin vary across different tissues, mediating distinct developmental outcomes and contributing to the functional diversity of auxin. However, the mechanisms that underlie these activities are poorly understood. Here we identify an auxin signalling mechanism, which acts in parallel to the canonical auxin pathway based on the transport inhibitor response1 (TIR1) and other auxin receptor F-box (AFB) family proteins (TIR1/AFB receptors)1,2, that translates levels of cellular auxin to mediate differential growth during apical-hook development. This signalling mechanism operates at the concave side of the apical hook, and involves auxin-mediated C-terminal cleavage of transmembrane kinase 1 (TMK1). The cytosolic and nucleus-translocated C terminus of TMK1 specifically interacts with and phosphorylates two non-canonical transcriptional repressors of the auxin or indole-3-acetic acid (Aux/IAA) family (IAA32 and IAA34), thereby regulating ARF transcription factors. In contrast to the degradation of Aux/IAA transcriptional repressors in the canonical pathway, the newly identified mechanism stabilizes the non-canonical IAA32 and IAA34 transcriptional repressors to regulate gene expression and ultimately inhibit growth. The auxin-TMK1 signalling pathway originates at the cell surface, is triggered by high levels of auxin and shares a partially overlapping set of transcription factors with the TIR1/AFB signalling pathway. This allows distinct interpretations of different concentrations of cellular auxin, and thus enables this versatile signalling molecule to mediate complex developmental outcomes.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Sequência de Aminoácidos , Arabidopsis/citologia , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas F-Box/metabolismo , Ácidos Indolacéticos/antagonistas & inibidores , Mutação , Reguladores de Crescimento de Plantas/antagonistas & inibidores , Ligação Proteica , Proteínas Serina-Treonina Quinases/genética , Receptores de Superfície Celular/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
6.
Nucleic Acids Res ; 51(21): 11568-11583, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-37850650

RESUMO

The cistrome consists of all cis-acting regulatory elements recognized by transcription factors (TFs). However, only a portion of the cistrome is active for TF binding in a specific tissue. Resolving the active cistrome in plants remains challenging. In this study, we report the assay sequential extraction assisted-active TF identification (sea-ATI), a low-input method that profiles the DNA sequences recognized by TFs in a target tissue. We applied sea-ATI to seven plant tissues to survey their active cistrome and generated 41 motif models, including 15 new models that represent previously unidentified cis-regulatory vocabularies. ATAC-seq and RNA-seq analyses confirmed the functionality of the cis-elements from the new models, in that they are actively bound in vivo, located near the transcription start site, and influence chromatin accessibility and transcription. Furthermore, comparing dimeric WRKY CREs between sea-ATI and DAP-seq libraries revealed that thermodynamics and genetic drifts cooperatively shaped their evolution. Notably, sea-ATI can identify not only positive but also negative regulatory cis-elements, thereby providing unique insights into the functional non-coding genome of plants.


Assuntos
Plantas , Fatores de Transcrição , Vocabulário , Cromatina , Ligação Proteica/genética , Sequências Reguladoras de Ácido Nucleico , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Plantas/genética
7.
Plant Physiol ; 192(3): 2243-2260, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37010107

RESUMO

The primary cell wall is a fundamental plant constituent that is flexible but sufficiently rigid to support the plant cell shape. Although many studies have demonstrated that reactive oxygen species (ROS) serve as important signaling messengers to modify the cell wall structure and affect cellular growth, the regulatory mechanism underlying the spatial-temporal regulation of ROS activity for cell wall maintenance remains largely unclear. Here, we demonstrate the role of the Arabidopsis (Arabidopsis thaliana) multicopper oxidase-like protein skewed 5 (SKU5) and its homolog SKU5-similar 1 (SKS1) in root cell wall formation through modulating ROS homeostasis. Loss of SKU5 and SKS1 function resulted in aberrant division planes, protruding cell walls, ectopic deposition of iron, and reduced nicotinamide adeninedinucleotide phosphate (NADPH) oxidase-dependent ROS overproduction in the root epidermis-cortex and cortex-endodermis junctions. A decrease in ROS level or inhibition of NADPH oxidase activity rescued the cell wall defects of sku5 sks1 double mutants. SKU5 and SKS1 proteins were activated by iron treatment, and iron over-accumulated in the walls between the root epidermis and cortex cell layers of sku5 sks1. The glycosylphosphatidylinositol-anchored motif was crucial for membrane association and functionality of SKU5 and SKS1. Overall, our results identified SKU5 and SKS1 as regulators of ROS at the cell surface for regulation of cell wall structure and root cell growth.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Parede Celular , Raízes de Plantas , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Parede Celular/metabolismo , Ferro/metabolismo , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Oxirredução , Oxirredutases/genética , Oxirredutases/metabolismo , Espécies Reativas de Oxigênio/metabolismo
8.
Exp Cell Res ; 427(1): 113572, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36990422

RESUMO

Long non-coding RNAs (lncRNAs) are pivotal regulators in heart disease, including myocardial ischemia/reperfusion (I/R) injury. LncRNA just proximal to XIST (JPX) is a molecular switch for X-chromosome inactivation. Enhancer of zeste homolog 2 (EZH2) is a core catalytic subunit of the polycomb repressive complex 2 (PRC2), which is involved in chromatin compaction and gene repression. This study aims to explore the mechanism of JPX regulating the expression of Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) by binding to EZH2 and preventing cardiomyocyte I/R damage in vivo and in vitro. First, we constructed mouse myocardial I/R and HL1 cell hypoxia/reoxygenation models, and found that JPX was low expressed in both models. JPX overexpression alleviated cardiomyocyte apoptosis in vivo and in vitro, reduced the I/R-induced infarct size in mouse hearts, lowered the serum cTnI concentration, and promoted mouse cardiac systolic function. The evidence implies that JPX can alleviate I/R-induced acute cardiac damage. Mechanistically, the FISH and RIP assays showed that JPX could bind to EZH2. The ChIP assay revealed EZH2 enrichment at the promoter region of SERCA2a. Both the EZH2 and H3K27me3 levels at the promoter region of SERCA2a were reduced in the JPX overexpression group compared to those in the Ad-EGFP group (P < 0.01). In summary, our results suggested that LncRNA JPX directly bound to EZH2 and reduced the EZH2-mediated H3K27me3 in the SERCA2a promoter region, protecting the heart from acute myocardial I/R injury. Therefore, JPX might be a potential therapeutic target for I/R injury.


Assuntos
Traumatismo por Reperfusão Miocárdica , RNA Longo não Codificante , Camundongos , Animais , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Histonas/metabolismo , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Apoptose/genética
9.
Proc Natl Acad Sci U S A ; 118(24)2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34099554

RESUMO

Differential concentrations of phytohormone trigger distinct outputs, which provides a mechanism for the plasticity of plant development and an adaptation strategy among plants to changing environments. However, the underlying mechanisms of the differential responses remain unclear. Here we report that a high concentration of auxin, distinct from the effect of low auxin concentration, enhances abscisic acid (ABA) responses in Arabidopsis thaliana, which partially relies on TRANS-MEMBERANE KINASE 1 (TMK1), a key regulator in auxin signaling. We show that high auxin and TMK1 play essential and positive roles in ABA signaling through regulating ABA INSENSITIVE 1 and 2 (ABI1/2), two negative regulators of the ABA pathway. TMK1 inhibits the phosphatase activity of ABI2 by direct phosphorylation of threonine 321 (T321), a conserved phosphorylation site in ABI2 proteins, whose phosphorylation status is important for both auxin and ABA responses. This TMK1-dependent auxin signaling in the regulation of ABA responses provides a possible mechanism underlying the high auxin responses in plants and an alternative mechanism involved in the coordination between auxin and ABA signaling.


Assuntos
Ácido Abscísico/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Epistasia Genética , Fosforilação , Fosfotreonina/metabolismo , Ligação Proteica
10.
Int Heart J ; 65(2): 292-299, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38556337

RESUMO

B-type natriuretic peptide (BNP) possesses protective cardiovascular properties; however, there has not been sufficient serious consideration of the side effects of BNP. As for sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a), it was once considered a new target for the treatment of heart failure (HF). Nevertheless, clinical trials of SERCA2a gene therapy in HF have finally become unsuccessful. Research has found that elevated BNP levels and decreased SERCA2a expression are two important HF characteristics, which are always negatively correlated. We hypothesize that BNP inhibits SERCA2a expression and, therefore, exerts negative effects on SERCA2a expression and function.The effects of BNP on endogenous SERCA2a expression and function were tested in mice with HF induced by transverse aortic constriction and neonatal rat cardiomyocytes (NRCM). Furthermore, to verify the effects of BNP on exogenous SERCA2a gene transduction efficacy, BNP was added to the myocardium and cardiomyocytes infected with an adenovirus overexpressing SERCA2a.In vivo, BNP levels were increased, SERCA2a expression was reduced in both the BNP intervention and HF groups, and BNP reduced the overexpressed exogenous SERCA2a protein in the myocardium. Our in vitro data showed that BNP dose-dependently inhibited the total and exogenous SERCA2a expression in NRCM by activating the cGMP-dependent protein kinase G. BNP also inhibited the effects of SERCA2a overexpression on Ca2+ transience in NRCM.The expression and function of endogenous and exogenous SERCA2a are inhibited by BNP. The opposite relationship between BNP and SERCA2a should be given serious attention in the treatment of HF via BNP or SERCA2a gene therapy.


Assuntos
Insuficiência Cardíaca , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático , Ratos , Camundongos , Animais , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Peptídeo Natriurético Encefálico/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo
11.
Plant Cell ; 32(1): 226-241, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31649122

RESUMO

Age and wounding are two major determinants for regeneration. In plants, the root regeneration is triggered by wound-induced auxin biosynthesis. As plants age, the root regenerative capacity gradually decreases. How wounding leads to the auxin burst and how age and wound signals collaboratively regulate root regenerative capacity are poorly understood. Here, we show that the increased levels of three closely-related miR156-targeted Arabidopsis (Arabidopsis thaliana) SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors, SPL2, SPL10, and SPL11, suppress root regeneration with age by inhibiting wound-induced auxin biosynthesis. Mechanistically, we find that a subset of APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factors including ABSCISIC ACID REPRESSOR1 and ERF109 is rapidly induced by wounding and serves as a proxy for wound signal to induce auxin biosynthesis. In older plants, SPL2/10/11 directly bind to the promoters of AP2/ERFs and attenuates their induction, thereby dampening auxin accumulation at the wound. Our results thus identify AP2/ERFs as a hub for integration of age and wound signal for root regeneration.


Assuntos
Proteínas de Arabidopsis/metabolismo , Etilenos/metabolismo , Proteínas de Homeodomínio/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Regeneração/fisiologia , Ácido Abscísico/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Homeodomínio/genética , Ácidos Indolacéticos/metabolismo , MicroRNAs/metabolismo , Proteínas Nucleares , Regiões Promotoras Genéticas , Regeneração/genética , Proteínas Repressoras , Fatores de Transcrição/metabolismo
12.
Heart Vessels ; 38(1): 40-48, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35915265

RESUMO

This study was designed to assess coronary microvascular obstruction (MVO) in patients with acute ST-segment elevation myocardial infarction (STEMI) by cardiac magnetic resonance T2-weighted short tau inversion recovery (T2-STIR) image and layer-specific analysis of 2-dimensional speckle tracking echocardiography combined with low-dose dobutamine stress echocardiography (LDDSE-LS2D-STE). 32 patients were enrolled to perform cardiac magnetic resonance and echocardiography 5-7 days after primary percutaneous coronary intervention. Infarcted myocardium was categorized into MVO+ group and MVO- group by late gadolinium enhancement as gold standard. At T2-weighted image, the area of hyper-intense region and hypo-intense core inside were marked as A1, A2 and A2/A1 > 0 represented MVO. Strain parameters were composed of longitudinal strain (LS), circumferential strain and radial strain at rest and dobutamine stress. There were 94 MVO+ segments, 136 MVO- segments according to gold standard. 96 segments had hypo-intense core at T2-STIR image. The sensitivity and specificity of T2-STIR in detecting MVO were 91.49 and 92.65%. Endocardial LS was superior to other parameters, and stress endocardial LS was higher than that of resting endocardial LS (sensitivity: 77.11% vs 72.29%, specificity: 93.28% vs 83.19%, AUC: 0.87 vs 0.82, P < 0.05). The combination of T2-STIR and stress endocardial LS in parallel test could improve sensitivity significantly (98.05% vs 91.49%). T2-STIR has higher diagnostic value in detecting MVO with some limitations. However, LDDSE-LS2D-STE with cost-effective and handling may be a good alternative to T2-STIR. It provides additional and reliable diagnostic tools to identify MVO in STEMI patients after reperfusion.


Assuntos
Oclusão Coronária , Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Ecocardiografia sob Estresse , Infarto do Miocárdio/patologia , Meios de Contraste , Gadolínio , Ecocardiografia/métodos , Espectroscopia de Ressonância Magnética , Imagem Cinética por Ressonância Magnética
13.
BMC Public Health ; 23(1): 1862, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37752456

RESUMO

BACKGROUND: In previous studies, sun-protective behaviors increased cardiovascular incidence. Our present article is to further analyze the potential relationship between sun-protective behaviors (staying in the shade, wearing long-sleeved clothing, and applying sunscreen) and hypertension. METHOD: The present cross-sectional study evaluated 8,613 participants (aged 20-60 years) from the National Health and Nutrition Examination Survey (NHANES) obtained between 2009 and 2014. We performed multiple logistic regression analysis to examine the relationship between sun-protective behaviors and hypertension. Subgroup analysis was then performed. Multiple linear regression analysis was utilized to examine the relationship of sun-protective behaviors and each sun-protective behavior with systolic and diastolic blood pressure, stratified by sex and race. RESULTS: A total of 8,613 participants (weighted n = 127,909,475) were applied in our study, including 1,694 hypertensive subjects. Our study demonstrated that sun-protective behaviors of the 2-3 category were associated with increased risk of hypertension, but not with higher systolic and diastolic blood pressure. In subgroup analysis, men, Mexican American, and 25 < BMI ≤ 30 who reported sun-protective behaviors (2-3) were prone to hypertension. Multiple linear regression models showed that non-Hispanic white men with sun-protective behaviors (2-3) were positively associated with systolic and diastolic blood pressure. The association between other-Hispanic men with frequent wearing long-sleeved clothing and diastolic blood pressure was positively correlated. CONCLUSION: Sun-protective behaviors of the 2-3 category could increase the incidence of hypertension, but not increase systolic and diastolic blood pressure. We only found that non-Hispanic white men who reported sun-protective behaviors (2-3) were positively associated with systolic and diastolic blood pressure. These findings suggested that excessive sun-protective behaviors should be avoided.


Assuntos
Hipertensão , Neoplasias Cutâneas , Masculino , Humanos , Inquéritos Nutricionais , Estudos Transversais , Comportamentos Relacionados com a Saúde , Hipertensão/epidemiologia , Hipertensão/prevenção & controle , Hipertensão/tratamento farmacológico , Protetores Solares/uso terapêutico
14.
Proc Natl Acad Sci U S A ; 117(23): 13127-13137, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32434921

RESUMO

Stomatal guard cells control gas exchange that allows plant photosynthesis but limits water loss from plants to the environment. In Arabidopsis, stomatal development is mainly controlled by a signaling pathway comprising peptide ligands, membrane receptors, a mitogen-activated protein kinase (MAPK) cascade, and a set of transcription factors. The initiation of the stomatal lineage requires the activity of the bHLH transcription factor SPEECHLESS (SPCH) with its partners. Multiple kinases were found to regulate SPCH protein stability and function through phosphorylation, yet no antagonistic protein phosphatase activities have been identified. Here, we identify the conserved PP2A phosphatases as positive regulators of Arabidopsis stomatal development. We show that mutations in genes encoding PP2A subunits result in lowered stomatal production in Arabidopsis Genetic analyses place the PP2A function upstream of SPCH. Pharmacological treatments support a role for PP2A in promoting SPCH protein stability. We further find that SPCH directly binds to the PP2A-A subunits in vitro. In plants, nonphosphorylatable SPCH proteins are less affected by PP2A activity levels. Thus, our research suggests that PP2A may function to regulate the phosphorylation status of the master transcription factor SPCH in stomatal development.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Regulação da Expressão Gênica de Plantas/fisiologia , Estômatos de Plantas/crescimento & desenvolvimento , Proteína Fosfatase 2/metabolismo , Proteínas de Arabidopsis/antagonistas & inibidores , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/isolamento & purificação , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Mutação , Fosforilação/fisiologia , Estômatos de Plantas/efeitos dos fármacos , Plantas Geneticamente Modificadas , Proteína Fosfatase 2/antagonistas & inibidores , Proteína Fosfatase 2/genética , Proteína Fosfatase 2/isolamento & purificação , Estabilidade Proteica/efeitos dos fármacos , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Nicotiana/genética
15.
J Integr Plant Biol ; 65(2): 343-370, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36610013

RESUMO

Asymmetric cell division (ACD) is a fundamental process that generates new cell types during development in eukaryotic species. In plant development, post-embryonic organogenesis driven by ACD is universal and more important than in animals, in which organ pattern is preset during embryogenesis. Thus, plant development provides a powerful system to study molecular mechanisms underlying ACD. During the past decade, tremendous progress has been made in our understanding of the key components and mechanisms involved in this important process in plants. Here, we present an overview of how ACD is determined and regulated in multiple biological processes in plant development and compare their conservation and specificity among different model cell systems. We also summarize the molecular roles and mechanisms of the phytohormones in the regulation of plant ACD. Finally, we conclude with the overarching paradigms and principles that govern plant ACD and consider how new technologies can be exploited to fill the knowledge gaps and make new advances in the field.


Assuntos
Divisão Celular Assimétrica , Plantas , Animais , Desenvolvimento Vegetal , Reguladores de Crescimento de Plantas , Polaridade Celular/fisiologia
16.
Cell Commun Signal ; 20(1): 38, 2022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-35331264

RESUMO

BACKGROUND: The incidence of coronary heart disease (CHD) in premenopausal women is significantly lower than that of men of the same age, suggesting protective roles of estrogen for the cardiovascular system against CHD. This study aimed to confirm the protective effect of estrogen on myocardium during myocardial ischemia/reperfusion (MI/R) injury and explore the underlying mechanisms. METHODS: Neonatal rat cardiomyocytes and Sprague-Dawley rats were used in this study. Different groups were treated by bilateral ovariectomy, 17ß-estradiol (E2), adenoviral infection, or siRNA transfection. The expression of sarcoplasmic reticulum Ca2+ ATPase pump (SERCA2a) and endoplasmic reticulum (ER) stress-related proteins were measured in each group to examine the effect of different E2 levels and determine the relationship between SERCA2a and ER stress. The cell apoptosis, myocardial infarction size, levels of apoptosis and serum cardiac troponin I, ejection fraction, calcium transient, and morphology changes of the myocardium and ER were examined to verify the effects of E2 on the myocardium. RESULTS: Bilateral ovariectomy resulted in reduced SERCA2a levels and more severe MI/R injury. E2 treatment increased SERCA2a expression. Both E2 treatment and exogenous SERCA2a overexpression decreased levels of ER stress-related proteins and alleviated myocardial damage. In contrast, SERCA2a knockdown exacerbated ER stress and myocardial damage. Addition of E2 after SERCA2a knockdown did not effectively inhibit ER stress or reduce myocardial injury. CONCLUSIONS: Our data demonstrate that estrogen inhibits ER stress and attenuates MI/R injury by upregulating SERCA2a. These results provide a new potential target for therapeutic intervention and drug discovery in CHD. Video Abstract.


Assuntos
Estresse do Retículo Endoplasmático , Estrogênios , Traumatismo por Reperfusão Miocárdica , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático , Animais , Apoptose , Estrogênios/farmacologia , Feminino , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos , Ratos , Ratos Sprague-Dawley , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
17.
BMC Cardiovasc Disord ; 22(1): 386, 2022 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-36030211

RESUMO

INTRODUCTION: To develop and validate clinical evaluators that predict adverse left ventricular remodeling (ALVR) in non-ST-elevation myocardial infarction (NSTEMI) patients after primary percutaneous coronary intervention (PCI). METHODS: The retrospective study analyzed the clinical data of 507 NSTEMI patients who were treated with primary PCI from the Affiliated Hospital of Xuzhou Medical University and the Second Affiliated Hospital of Xuzhou Medical University, between January 1, 2019 and September 31, 2021. The training cohort consisted of patients admitted before June 2020 (n = 287), and the remaining patients (n = 220) were assigned to an external validation cohort. The endpoint event was the occurrence of ALVR, which was described as an increase ≥ 20% in left ventricular end-diastolic volume (LVEDV) at 3-4 months follow-up CMR compared with baseline measurements. The occurrence probability of ALVR stemmed from the final model, which embodied independent predictors recommended by logistic regression analysis. The area under the receiver operating characteristic curve (AUC), Calibration plot, Hosmer-Lemeshow method, and decision curve analysis (DCA) were applied to quantify the performance. RESULTS: Independent predictors for ALVR included age (odds ratio (OR): 1.040; 95% confidence interval (CI): 1.009-1.073), the level of neutrophil to lymphocyte ratio (OR: 4.492; 95% CI: 1.906-10.582), the cardiac microvascular obstruction (OR: 3.416; 95% CI: 1.170-9.970), peak global longitudinal strain (OR: 1.131; 95% CI: 1.026-1.246), infarct size (OR: 1.082; 95% CI: 1.042-1.125) and left ventricular ejection fraction (OR: 0.925; 95% CI: 0.872-0.980), which were screened by regression analysis then merged into the nomogram model. Both internal validation (AUC: 0.805) and external validation (AUC: 0.867) revealed that the prediction model was capable of good discrimination. Calibration plot and Hosmer-Lemeshow method showed high consistency between the probabilities predicted by the nomogram (P = 0.514) and the validation set (P = 0.762) and the probabilities of actual occurrence. DCA corroborated the clinical utility of the nomogram. CONCLUSIONS: In this study, the proposed nomogram model enabled individualized prediction of ALVR in NSTEMI patients after reperfusion and conduced to guide clinical therapeutic schedules.


Assuntos
Infarto do Miocárdio sem Supradesnível do Segmento ST , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Valor Preditivo dos Testes , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda , Remodelação Ventricular
18.
Proc Natl Acad Sci U S A ; 116(42): 21285-21290, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31570617

RESUMO

In both plants and animals, multiple cellular processes must be orchestrated to ensure proper organogenesis. The cell division patterns control the shape of growing organs, yet how they are precisely determined and coordinated is poorly understood. In plants, the distribution of the phytohormone auxin is tightly linked to organogenesis, including lateral root (LR) development. Nevertheless, how auxin regulates cell division pattern during lateral root development remains elusive. Here, we report that auxin activates Mitogen-Activated Protein Kinase (MAPK) signaling via transmembrane kinases (TMKs) to control cell division pattern during lateral root development. Both TMK1/4 and MKK4/5-MPK3/6 pathways are required to properly orient cell divisions, which ultimately determine lateral root development in response to auxin. We show that TMKs directly and specifically interact with and phosphorylate MKK4/5, which is required for auxin to activate MKK4/5-MPK3/6 signaling. Our data suggest that TMK-mediated noncanonical auxin signaling is required to regulate cell division pattern and connect auxin signaling to MAPK signaling, which are both essential for plant development.


Assuntos
Divisão Celular/genética , Ácidos Indolacéticos/metabolismo , Organogênese Vegetal/genética , Desenvolvimento Vegetal/genética , Raízes de Plantas/genética , Transdução de Sinais/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Fosforilação/genética
19.
Proc Natl Acad Sci U S A ; 116(28): 14349-14357, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31239335

RESUMO

Endocytosis is essential to all eukaryotes, but how cargoes are selected for internalization remains poorly characterized. Extracellular cargoes are thought to be selected by transmembrane receptors that bind intracellular adaptors proteins to initiate endocytosis. Here, we report a mechanism for clathrin-mediated endocytosis (CME) of extracellular lanthanum [La(III)] cargoes, which requires extracellular arabinogalactan proteins (AGPs) that are anchored on the outer face of the plasma membrane. AGPs were colocalized with La(III) on the cell surface and in La(III)-induced endocytic vesicles in Arabidopsis leaf cells. Superresolution imaging showed that La(III) triggered AGP movement across the plasma membrane. AGPs were then colocalized and physically associated with the µ subunit of the intracellular adaptor protein 2 (AP2) complexes. The AGP-AP2 interaction was independent of CME, whereas AGP's internalization required CME and AP2. Moreover, we show that AGP-dependent endocytosis in the presence of La(III) also occurred in human cells. These findings indicate that extracellular AGPs act as conserved CME cargo receptors, thus challenging the current paradigm about endocytosis of extracellular cargoes.


Assuntos
Endocitose/genética , Galactanos/metabolismo , Lantânio/farmacologia , Metais Terras Raras/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/genética , Membrana Celular/efeitos dos fármacos , Clatrina/química , Endocitose/efeitos dos fármacos , Galactanos/genética , Humanos , Lantânio/química , Lantânio/metabolismo , Metais Terras Raras/química , Metais Terras Raras/metabolismo , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo
20.
J Integr Plant Biol ; 64(12): 2425-2437, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36250442

RESUMO

Callus induction, which results in fate transition in plant cells, is considered as the first and key step for plant regeneration. This process can be stimulated in different tissues by a callus-inducing medium (CIM), which contains a high concentration of phytohormone auxin. Although a few key regulators for callus induction have been identified, the multiple aspects of the regulatory mechanism driven by high levels of auxin still need further investigation. Here, we find that high auxin induces callus through a H3K36 histone methylation-dependent mechanism, which requires the methyltransferase SET DOMAIN GROUP 8 (SDG8). During callus induction, the increased auxin accumulates SDG8 expression through a TIR1/AFBs-based transcriptional regulation. SDG8 then deposits H3K36me3 modifications on the loci of callus-related genes, including a master regulator WOX5 and the cell proliferation-related genes, such as CYCB1.1. This epigenetic regulation in turn is required for the transcriptional activation of these genes during callus formation. These findings suggest that the massive transcriptional reprogramming for cell fate transition by auxin during callus formation requires epigenetic modifications including SDG8-mediated histone H3K36 methylation. Our results provide insight into the coordination between auxin signaling and epigenetic regulation during fundamental processes in plant development.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Histonas/metabolismo , Metilação , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Ácidos Indolacéticos/farmacologia , Ácidos Indolacéticos/metabolismo , Epigênese Genética , Domínios PR-SET , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Regulação da Expressão Gênica de Plantas
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