Expressions of matrix metalloproteinases and their inhibitor are modified by beta-adrenergic agonist Ractopamine in skeletal fibroblasts and myoblasts.

摘要

The beta-adrenergic agonist ractopamine is known to promote growth and improve feed efficiency in animal production, in part by suppressing muscle protein degradation. This investigation aims to determine whether ractopamine modifies the expression of enzymes principally involved in intramuscular connective tissue turnover, the matrix metalloproteinases (MMPs) and their inhibitors, in the principal cell types of skeletal muscle. Mouse skeletal muscle fibroblasts (NOR-10 cells) and myoblasts (C2C12 cells) were cultured with or without 2 or 10 micro M ractopamine for 6 or 24 h. Cellular MMP-2 expression was increased (P<0.05) by ractopamine in both cell lines. Cellular MMP-3 expression was also increased in response to ractopamine in myoblasts (P<0.03). The amount of a tissue inhibitor of MMPs (TIMP-1) in cell lysates of both cell lines was increased (P<0.05) by the 6-h ractopamine treatment. The extracellular expression of MMP-2 and TIMP-1 was increased (P<0.05) in myoblasts, but not in fibroblasts. The elevated TIMP-1 expression in medium is in the order of three times higher (P<0.02) than the increased activity of MMP-2 expressed by myoblasts at 6 h. In summary, ractopamine treatment results in a higher cellular expression of MMP-2 and MMP-3 as compared with the expression of their inhibitor TIMP-1. However, the increased extracellular MMP-2 activity is counterbalanced by the increased presence of TIMP-1. The findings show that ractopamine has the potential to alter connective tissue turnover in treated animals.