Premium
INCREASED CARBONYLATION OF VENTRICULAR MYOSIN HEAVY CHAINS DURING DIABETES
Author(s) -
Bidasee Keshore R,
Rozanski George J,
Nagai Ryoji,
Horiuchi Seikoh,
Stockdale Frank,
Patel Kaushik,
Shao ChunHong
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.989.7
Subject(s) - chemistry , myosin , medicine , endocrinology , streptozotocin , major histocompatibility complex , diabetes mellitus , cardiac function curve , biochemistry , heart failure , gene
The present study was undertaken to assess whether ventricular myosin heavy chains (MHC) become carbonylated during diabetes and whether formation of these adducts impairs MHC function and the force of cardiac contractions. Type 1 diabetes was induced in male Sprague‐Dawley rats using streptozotocin (STZ). Two weeks after STZ injection, diabetic rats were randomly divided into two groups. One group of diabetic rats was treated with aminoguanidine via drinking water while the other received no treatment. After eight weeks of diabetes basal cardiac ejection fraction, fractional shortening, rate of left ventricular pressure increase and myocyte evoked shortening decreased by 9%, 16%, 34% and 18%. MHC‐β was the dominant isozyme, accounting for 86% of total MHC proteins. Ca 2+ ‐ and Mg 2+ ‐actomyosin ATPase activities and peak actomyosin syneresis (strong myosin‐actin interactions) were reduced by 35%, 28%, and 72%. Trypsin digestion and mass spectrometric analysis revealed elevated levels of carbonyl adducts on MHC‐β and MHC‐α. Crosslinking pentosidine adducts were also found on MHC using adduct‐specific antibodies. Six weeks of aminoguanidine treatment blunted reductions in cardiac function and MHC activity. Aminoguanidine treatment also significantly reduced formation of carbonyl adducts on MHC without altering MHC ratio. These new data suggest that in addition to isozyme switching, carbonylation of MHC contributes to the reduction in the force of cardiac contractions during diabetes (Supported by ADA and NIH).