PKC translocation and ERK1/2 activation in compensated right ventricular hypertrophy secondary to chronic emphysema.
BACKGROUND
Right ventricular hypertrophy (RVH) is an important complication of chronic lung disease. However, the signal transduction pathways involved as well as the physiological changes to the right ventricle have not been investigated. Emphysema was produced in male, Syrian Golden hamsters by intra-tracheal instillation of 250 IU/kg elastase (Emp, n = 17). Saline treated animals served as controls (Con, n = 15).


RESULTS
Nine months later, Emp hamsters had 75% greater lung volume, and evidence of RVH at the gross and myocyte level (RV:tibia length Emp 6.84 +/- 1.18 vs. Con 5.14 +/- 1.11 mg/mm; myocyte cross sectional area Emp 3737 vs. Con 2695 microm2), but not left ventricular hypertrophy. Serial echocardiographic analysis from baseline to nine months after induction of emphysema revealed increasing right ventricular internal dimension and decreased pulmonary artery acceleration time only in Emp hamsters. There was an increase in translocation of PKC betaI and PKC epsilon from cytosolic to membranous cell fractions in RV of Emp hamsters. Phosphorylation of PKC epsilon was unchanged. Translocation of PKC alpha and betaII were unchanged. Emp animals had a 22% increase in phospho-ERK 1/2, but no change in levels of total ERK 1/2 compared to Con.


CONCLUSIONS
These data suggest that PKC betaI, epsilon and ERK 1/2 may play a role in mediating compensated RVH secondary to emphysema and may have clinical relevance in the pathogenesis of RVH.
Avelar
Erick
E
Division of Nutrition, University of Utah, Salt Lake City, UT 84112, USA. erick.avelar@hsc.utah.edu <erick.avelar@hsc.utah.edu>
Jalili
Thunder
T
Dong
Li
L
Arvizo
Joel
J
Hu
Ping
P
Litwin
Sheldon E
SE
Mattson
John P
JP
D000818:Animals; D001692:Biological Transport; D002908:Chronic Disease; D006224:Cricetinae; D004452:Echocardiography; D004646:Emphysema / Q000150:complications*; D004789:Enzyme Activation; D017380:Hypertrophy, Right Ventricular / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000209:etiology*; D008297:Male; D008647:Mesocricetus; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D051744:Protein Kinase C-epsilon / Q000378:metabolism
D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051744:Protein Kinase C-epsilon; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3