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
• 负责人: Bruce, Heather
• 金额: $ 2.19万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=612346
• 关键词: Alteration; collagen; synthesis; cross; link

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.

使用β-肾上腺素能激动剂（ß-AA），例如克伦特罗作为人类医学中的支气管扩张剂来控制哮喘和慢性阻塞性疾病的症状。随着肌肉细胞中胶原蛋白的积累增加，导致心脏和骨骼肌肉组织探测。在加拿大，随着促销剂增加瘦肉和饲料的饲料。已经增加了韧性的增加。 RAC，p <0.001）USCLE（2.86对2.60 nmol pyr/g原始肌肉，控制对与RAC，p <0.05）基础（HGP）。但是，它在摩尔Trol与经过处理的胶原蛋白crlagenk ehrlich的Chromogen（EC）和每克原始肌肉基础上（4.34至4.78 nmol /g原始肌肉，控制与治疗，p <0.05） PYR/MOL胶原蛋白（P <0.1）。尸体组成是众所周知的，它们对肌内胶原蛋白的影响不是AA的施用，而HGP会影响Matlagen胶原蛋白交联的密度，并将其更改为胶原蛋白。 AA在骨骼肌胶原蛋白中产生了不同的结构修饰，表明胶原蛋白论文和周转率显着不同，以阐明ß化学途径，通过这些途径，这些目标是这些目标在这些目标中是下一个逻辑步骤。致力于控制胶原蛋白的合成和交联的机制及其对肉类的影响在治疗人类损伤或疾病期间的组织Fissis的疗程将有助于培训六个高度合格的人。