Effect of adriamycin on expression and content of myocardial structural and regulatory proteins

• Published in: Kardiologiia Vol. 42; no. 9; p. 60
• Main Authors: Dudnakova, T V, Lakomkin, V L, Tsyplenkova, V G, Shekhonin, B V, Shirinskiĭ, V P, Kapel'ko, V I
• Format: Journal Article
• Language: Russian
• Published: Russia (Federation) 2002
• Subjects: Animals; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacology; Cytoskeletal Proteins - drug effects; Cytoskeletal Proteins - metabolism; Doxorubicin - adverse effects; Doxorubicin - pharmacology; Extracellular Matrix Proteins - drug effects; Extracellular Matrix Proteins - metabolism; Heart - drug effects; Myocardium - metabolism; Rats; Rats, Wistar
• ISSN: 0022-9040

The biochemical and morphological study of the cytoskeleton and extracellular matrix of rat heart was carried out after single injection of adriamycin (2.2 or 0.44 mg/kg). Hearts were taken for the study after 2 hours and 3 weeks after injection. The light and electronic microscopy, immunohistochemical determination of type I, III and IV collagens and fibronectin using specific antibodies were implied for morphological study; electrophoresis and immunoblotting were implied for the determination of the content of some proteins of cardiomyocytes (KRP or telokin, desmin, tubulin and vinculin), and extracellular matrix (fibronectin) and vascular smooth muscle cells (MLCK, myosin light chain kinase). Adriamycin injection in the dose 2.2 mg/kg which is close to therapeutic and known to alter intracellular membranes approximately in the half of cardiomyocytes, did not influence the relative volume and structure of collagen network but distinctly reduced the density of fibronectin-distribution. The content of tubulin, fibronectin, MLCK and KRP was significantly decreased by 18-24%, while contents of desmin and vinculin were changed insignificantly. After 3 weeks, an increased density and extension of collagen network indicating the development of diffuse fibrosis were observed. Contents of tubulin and KRP were increased above control level by 50 and 20%, respectively. Similar hyperrestitution of tubulin, fibronectin and KRP content by 15-25% was determined after smaller dose of adriamycin (0.44 mg/kg). Only content of MLCK out of proteins studied remained at lower level in both groups by 25-34%. Isolated chick embryo cardiomyocytes subjected to adriamycin responded by increased level of KRP expression by 20% in 4 days while the level of tubulin expression remained unchanged. Results showed that damage of cardiomyocytes and extracellular matrix after single injection of adriamycin in the dose close to therapeutic was followed by increased expression of some proteins of cytoskeleton and extracellular matrix. KRP seems to play active role in this reparative response while the steadily reduced level of MLCK expression may disturb the control of coronary vessels.