Alteration of collagen synthesis and cross-link profile by beta-adrenergic agonists

β-肾上腺素能激动剂改变胶原合成和交联特征

基本信息

  • 批准号:
    RGPIN-2014-06641
  • 负责人:
  • 金额:
    $ 2.19万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Discovery Grants Program - Individual
  • 财政年份:
    2018
  • 资助国家:
    加拿大
  • 起止时间:
    2018-01-01 至 2019-12-31
  • 项目状态:
    已结题

项目摘要

The use of beta-adrenergic agonists (ß-AA) such as clenbuterol as bronchial dilators in human medicine to control the symptoms of asthma and chronic pulmonary obstructive disease is widespread. Long-term (greater than or equal to one day) use is associated with increased accumulation of collagen in muscle cells, and can lead to both cardiac and skeletal muscle tissue diseases. This is a concern not only to human medicine but to animal agriculture as well because the ß-AA ractopamine hydrochloride (RAC) and zilpaterol hydrochloride (ZIL) are approved for use in Canada as growth promotants and re-partitioning agents to increase lean meat yield and feed efficiency in cattle. That RAC and ZIL have the potential to affect intramuscular collagen suggests that they may also affect meat eating quality because the quantity of collagen and the density of its mature, heat-stable crosslinks have been linked to increased toughness. Recent research by the applicant indicated that supplementation of cattle diets with RAC did not increase the total collagen in the muscles of cattle, but did decrease the density of the heat-stable collagen crosslink pyridinoline (PYR) on a molar (0.23 and 0.17 mole PYR/mole collagen, control versus RAC, P < 0.001) and per gram raw muscle (2.86 versus 2.60 nmol PYR/g raw muscle, control versus RAC, P < 0.05) basis. Further research by the applicant and her team showed that the implantation of beef cattle with estrogen-progesterone hormone growth promotants (HGP) also did not change total collagen concentration in the gluteus medius muscle (GM, top sirloin), but it did increase the concentration of another mature collagen crosslink Ehrlich's Chromogen (EC) on a molar (0.38 to 0.43 mol EC/mol collagen, control versus treated, P < 0.05) and per gram raw muscle basis (4.34 to 4.78 nmol/g raw muscle, control versus treated, P < 0.05). Additionally, there was a trend for the concentration of PYR to increase with HGP use from 0.18 (control) to 0.21 mol PYR/mol collagen (P < 0.1). These results suggested that the contribution of collagen to cooked beef toughness may decrease with ß-AA administration but increase with the use of steroidal growth promotants. The use of commercially available growth promoting substances in the beef industry is widespread and although their effects on body weight gain, feed efficiency and carcass composition are well known, their impact on intramuscular collagen is not. These results are the first to indicate that administration of ß-AA and HGP can affect the density of intramuscular mature collagen crosslinks and change the contribution of collagen to cooked beef toughness. That HGP and ß-AA produced different structural modifications in skeletal muscle collagen indicated that the mechanisms of collagen synthesis and turnover in response to these growth promotants were markedly different; consequently, the short term objectives of the proposed research are to elucidate the biochemical pathways by which ß-AA and HGP affect collagen crosslinking. These objectives are the next logical steps in a long term research program devoted to investigating the mechanisms controlling the synthesis and crosslinking of collagen and its impact on meat quality. This research is fundamental to fully understand the control mechanisms of collagen synthesis systemically and will have broad applications not only for animal production but for the prevention of tissue fibrosis during the treatment of human injury or disease and will contribute to the training of six highly qualified personnel.
β-肾上腺素能激动剂(β-AA)如克仑特罗在人类医学中作为支气管扩张剂以控制哮喘和慢性肺阻塞性疾病的症状是广泛使用的。 长期(大于或等于一天)使用与肌肉细胞中胶原蛋白积聚增加有关,并可能导致心脏和骨骼肌组织疾病。 这不仅是人类医学的关注点,而且也是畜牧业的关注点,因为在加拿大批准将A-AA盐酸莱克多巴胺(RAC)和盐酸齐帕特罗(ZIL)用作生长促进剂和再分配剂,以增加牛的瘦肉产量和饲料效率。 RAC和ZIL有可能影响肌内胶原蛋白,这表明它们也可能影响肉类食用质量,因为胶原蛋白的数量及其成熟的热稳定交联密度与韧性增加有关。 申请人最近的研究表明,用RAC补充牛饮食不会增加牛肌肉中的总胶原蛋白,但确实降低了摩尔胶原蛋白上的热稳定胶原蛋白交联吡啶啉(PYR)的密度。(0.23和0.17摩尔PYR/摩尔胶原,对照对RAC,P < 0.001)和每克生肌(2.86对2.60 nmol PYR/g生肌,对照对RAC,P < 0.05)基础。 申请人及其团队的进一步研究表明,用雌激素-孕酮激素生长促进剂(HGP)植入肉牛也没有改变臀中肌中的总胶原蛋白浓度(GM,顶级牛腩),但它确实增加了另一种成熟胶原交联埃利希色原(EC)在磨牙上的浓度(0.38至0.43 mol EC/mol胶原,对照组与处理组,P < 0.05)和每克生肌基础(4.34至4.78 nmol/g生肌,对照组与处理组,P < 0.05)。 此外,PYR的浓度有随着HGP的使用而增加的趋势,从0.18(对照)增加到0.21 mol PYR/mol胶原(P < 0.1)。 这些结果表明,胶原蛋白对煮熟的牛肉韧性的贡献可能会随着α-AA的施用而减少,但随着类固醇生长促进剂的使用而增加。 在牛肉工业中广泛使用市售的生长促进物质,尽管它们对体重增加、饲料效率和胴体组成的影响是众所周知的,但它们对肌内胶原蛋白的影响却不是。 这些结果首次表明,给予α-AA和HGP可以影响肌内成熟胶原交联的密度,并改变胶原对熟牛肉韧性的贡献。 HGP和HGP-AA在骨骼肌胶原中产生不同的结构修饰,这表明胶原合成和周转对这些生长促进剂的反应机制明显不同;因此,拟议研究的短期目标是阐明HGP-AA和HGP影响胶原交联的生化途径。这些目标是长期研究计划的下一个逻辑步骤,该计划致力于研究控制胶原蛋白合成和交联的机制及其对肉质的影响。 这项研究对于全面了解胶原蛋白合成的控制机制是至关重要的,不仅对动物生产,而且对预防人类损伤或疾病治疗期间的组织纤维化具有广泛的应用,并将有助于培养六名高素质的人员。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Bruce, Heather其他文献

Effects of independent versus dependent stressful life events on major symptom domains of schizophrenia.
  • DOI:
    10.1038/s41537-023-00415-3
  • 发表时间:
    2023-12-08
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Ma, Yizhou;Chiappelli, Joshua;Kvarta, Mark D.;Bruce, Heather;van der Vaart, Andrew;Goldwaser, Eric L.;Du, Xiaoming;Sampath, Hemalatha;Lightner, Samantha;Endres, Jane;Yusuf, Akram;Yuen, Alexa;Narvaez, Samantha;Campos-Saravia, Danny;Kochunov, Peter;Hong, L. Elliot
  • 通讯作者:
    Hong, L. Elliot
Cortical connectomic mediations on gamma band synchronization in schizophrenia.
  • DOI:
    10.1038/s41398-022-02300-6
  • 发表时间:
    2023-01-19
  • 期刊:
  • 影响因子:
    6.8
  • 作者:
    Du, Xiaoming;Hare, Stephanie;Summerfelt, Ann;Adhikari, Bhim M. M.;Garcia, Laura;Marshall, Wyatt;Zan, Peng;Kvarta, Mark;Goldwaser, Eric;Bruce, Heather;Gao, Si;Sampath, Hemalatha;Kochunov, Peter;Simon, Jonathan Z. Z.;Hong, L. Elliot
  • 通讯作者:
    Hong, L. Elliot
Association between brain similarity to severe mental illnesses and comorbid cerebral, physical, and cognitive impairments.
  • DOI:
    10.1016/j.neuroimage.2022.119786
  • 发表时间:
    2023-01
  • 期刊:
  • 影响因子:
    5.7
  • 作者:
    Ma, Yizhou;Kvarta, Mark D.;Adhikari, Bhim M.;Chiappelli, Joshua;Du, Xiaoming;van der Vaart, Andrew;Goldwaser, Eric L.;Bruce, Heather;Hatch, Kathryn S.;Gao, Si;Summerfelt, Ann;Jahanshad, Neda;Thompson, Paul M.;Nichols, Thomas E.;Hong, L. Elliot;Kochunov, Peter
  • 通讯作者:
    Kochunov, Peter
Cerebral blood flow and cardiovascular risk effects on resting brain regional homogeneity.
  • DOI:
    10.1016/j.neuroimage.2022.119555
  • 发表时间:
    2022-11-15
  • 期刊:
  • 影响因子:
    5.7
  • 作者:
    Adhikari, Bhim M.;Hong, L. Elliot;Zhao, Zhiwei;Wang, Danny J. J.;Thompson, Paul M.;Jahanshad, Neda;Zhu, Alyssa H.;Holiga, Stefan;Turner, Jessica A.;van Erp, Theo G. M.;Calhoun, Vince D.;Hatch, Kathryn S.;Bruce, Heather;Hare, Stephanie M.;Chiappelli, Joshua;Goldwaser, Eric L.;Kvarta, Mark D.;Ma, Yizhou;Du, Xiaoming;Nichols, Thomas E.;Shuldiner, Alan R.;Mitchell, Braxton D.;Dukart, Juergen;Chen, Shuo;Kochunov, Peter
  • 通讯作者:
    Kochunov, Peter

Bruce, Heather的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Bruce, Heather', 18)}}的其他基金

Formation of intramuscular collagen cross-links in cattle
牛肌内胶原交联的形成
  • 批准号:
    RGPIN-2021-02714
  • 财政年份:
    2022
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual
Validation of rapid evaporative ionization mass spectrometry (REIMS) for prediction of beef tenderness
验证快速蒸发电离质谱 (REIMS) 预测牛肉嫩度
  • 批准号:
    561225-2020
  • 财政年份:
    2021
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Alliance Grants
Formation of intramuscular collagen cross-links in cattle
牛肌内胶原交联的形成
  • 批准号:
    RGPIN-2021-02714
  • 财政年份:
    2021
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual
NSERC CREATE for the Canadian Meat Education and Training Network (MEaTnet) for Assuring Meat Safety and Quality
NSERC CREATE 为加拿大肉类教育和培训网络 (MEaTnet) 创建,以确保肉类安全和质量
  • 批准号:
    448107-2014
  • 财政年份:
    2019
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Collaborative Research and Training Experience
NSERC CREATE for the Canadian Meat Education and Training Network (MEaTnet) for Assuring Meat Safety and Quality
NSERC CREATE 为加拿大肉类教育和培训网络 (MEaTnet) 创建,以确保肉类安全和质量
  • 批准号:
    448107-2014
  • 财政年份:
    2018
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Collaborative Research and Training Experience
NSERC CREATE for the Canadian Meat Education and Training Network (MEaTnet) for Assuring Meat Safety and Quality
NSERC CREATE 为加拿大肉类教育和培训网络 (MEaTnet) 创建,以确保肉类安全和质量
  • 批准号:
    448107-2014
  • 财政年份:
    2017
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Collaborative Research and Training Experience
Alteration of collagen synthesis and cross-link profile by beta-adrenergic agonists
β-肾上腺素能激动剂改变胶原合成和交联特征
  • 批准号:
    RGPIN-2014-06641
  • 财政年份:
    2017
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual
Alteration of collagen synthesis and cross-link profile by beta-adrenergic agonists
β-肾上腺素能激动剂改变胶原合成和交联特征
  • 批准号:
    RGPIN-2014-06641
  • 财政年份:
    2016
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual
NSERC CREATE for the Canadian Meat Education and Training Network (MEaTnet) for Assuring Meat Safety and Quality
NSERC CREATE 为加拿大肉类教育和培训网络 (MEaTnet) 创建,以确保肉类安全和质量
  • 批准号:
    448107-2014
  • 财政年份:
    2016
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Collaborative Research and Training Experience
NSERC CREATE for the Canadian Meat Education and Training Network (MEaTnet) for Assuring Meat Safety and Quality
NSERC CREATE 为加拿大肉类教育和培训网络 (MEaTnet) 创建,以确保肉类安全和质量
  • 批准号:
    448107-2014
  • 财政年份:
    2015
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Collaborative Research and Training Experience

相似国自然基金

骨胶原(Bio-Oss Collagen)联合龈下喷砂+骨皮质切开术治疗 根分叉病变的临床疗效研究
  • 批准号:
    2024JJ9542
  • 批准年份:
    2024
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
靶向A2BR/CollagenⅠ通路抑制循环肿瘤细胞团形成阻断肺癌转移的机制研究
  • 批准号:
    82303467
  • 批准年份:
    2023
  • 资助金额:
    30 万元
  • 项目类别:
    青年科学基金项目
铜募集微纳米网片上调LOX活性稳定胶原网络促进盆底修复的研究
  • 批准号:
    82371638
  • 批准年份:
    2023
  • 资助金额:
    49.00 万元
  • 项目类别:
    面上项目
HRD1通过调控自噬介导肺纤维化肌成纤维细胞collagen-Ⅰ高分泌的机制研究
  • 批准号:
    82200080
  • 批准年份:
    2022
  • 资助金额:
    30 万元
  • 项目类别:
    青年科学基金项目
Collagen VI 通过线粒体代谢/巨噬细胞调节机制调控CINP 的发生发展
  • 批准号:
    2021JJ41060
  • 批准年份:
    2021
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
基于Collagen/GPVI通路调控肿瘤基质屏障/凝血屏障增强anti-PD-1治疗乳腺癌药效及机制研究
  • 批准号:
  • 批准年份:
    2021
  • 资助金额:
    30 万元
  • 项目类别:
    青年科学基金项目
肝星型细胞分泌 collagen I 激活盘状结构域受体DDR1-STAT3信号轴促进葡萄膜黑色素瘤肝转移的研究
  • 批准号:
    82003797
  • 批准年份:
    2020
  • 资助金额:
    16.0 万元
  • 项目类别:
    青年科学基金项目
四跨膜蛋白Tetraspanin 1结合Collagen I在特发性肺纤维化发病中的分子机制研究
  • 批准号:
  • 批准年份:
    2020
  • 资助金额:
    55 万元
  • 项目类别:
    面上项目
基于皮肤类器官模型探究TGFβ-Collagen-ROCK分子模块调控皮肤及其附属器官再生的机制
  • 批准号:
    82003384
  • 批准年份:
    2020
  • 资助金额:
    24.0 万元
  • 项目类别:
    青年科学基金项目
CDX2/MMP1/Collagen-I正反馈通路介导的细胞外基质重构在结直肠癌侵袭转移中的作用机制研究
  • 批准号:
    81972720
  • 批准年份:
    2019
  • 资助金额:
    55.0 万元
  • 项目类别:
    面上项目

相似海外基金

Preclinical Development of a Novel Therapeutic Agent for Idiopathic Pulmonary Fibrosis
特发性肺纤维化新型治疗剂的临床前开发
  • 批准号:
    10696538
  • 财政年份:
    2023
  • 资助金额:
    $ 2.19万
  • 项目类别:
Mechanical Causation of Corneal Stromal Matrix Synthesis and Fibrosis
角膜基质基质合成和纤维化的机械原因
  • 批准号:
    10659976
  • 财政年份:
    2023
  • 资助金额:
    $ 2.19万
  • 项目类别:
The non-canonical Collagen I-DDR1 signaling regulating protein synthesis during metastasis
非经典胶原蛋白 I-DDR1 信号在转移过程中调节蛋白质合成
  • 批准号:
    10607947
  • 财政年份:
    2023
  • 资助金额:
    $ 2.19万
  • 项目类别:
Interaction of fibroblasts with cell corpses increases collagen synthesis during lung repair
成纤维细胞与细胞尸体的相互作用增加了肺修复过程中的胶原蛋白合成
  • 批准号:
    10736792
  • 财政年份:
    2023
  • 资助金额:
    $ 2.19万
  • 项目类别:
CST6-mRNA activated matrices for efficient bone regeneration
CST6-mRNA 激活基质可实现高效骨再生
  • 批准号:
    10576944
  • 财政年份:
    2022
  • 资助金额:
    $ 2.19万
  • 项目类别:
Understanding and Manipulating Mechanics-Based Collagen Synthesis to Advance Functional Biomaterials
了解和操纵基于力学的胶原蛋白合成以推进功能性生物材料
  • 批准号:
    2140127
  • 财政年份:
    2022
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Standard Grant
A Model for Human Liver Fibrosis
人类肝纤维化模型
  • 批准号:
    10685178
  • 财政年份:
    2022
  • 资助金额:
    $ 2.19万
  • 项目类别:
Novel Biomarkers for Post-Liver Transplant NASH Fibrosis
肝移植后 NASH 纤维化的新型生物标志物
  • 批准号:
    10667657
  • 财政年份:
    2022
  • 资助金额:
    $ 2.19万
  • 项目类别:
Obesity promoting protein malonylation and chondrocyte metabolic dysfunction in osteoarthritis development
肥胖促进骨关节炎发展中的蛋白质丙二酰化和软骨细胞代谢功能障碍
  • 批准号:
    10424671
  • 财政年份:
    2022
  • 资助金额:
    $ 2.19万
  • 项目类别:
Aza-Heck/C-C cleavage/cross coupling cascades of pinene derivatives for the synthesis of zoanthamine alkaloids
蒎烯衍生物的 Aza-Heck/C-C 裂解/交叉偶联级联用于合成佐安胺生物碱
  • 批准号:
    10328890
  • 财政年份:
    2021
  • 资助金额:
    $ 2.19万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了