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Endurance Exercise is Associated with Decreased Calpain to Calpastatin Ratios in Aged Rat Hearts
Author(s) -
Sepe Joseph J,
Hacker Timothy A,
Diffee Gary M
Publication year - 2017
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.31.1_supplement.688.8
Subject(s) - calpastatin , calpain , sed , endurance training , medicine , treadmill , endocrinology , proteases , cardiac function curve , endogeny , chemistry , heart failure , biochemistry , enzyme
The Ca2+‐activated protease calpain has been shown to play a deleterious role in the heart during the aging process, which ultimately impacts cardiac function. Calpastatin is an endogenous inhibitor of calpain, and the ratio of calpain to calpastatin in cardiac myocytes is physiologically important because this ratio greatly impacts the ability of Ca2+ to activate calpain. It has been suggested that activation of calpain may lead to proteolytic degradation of sarcomeric proteins, which ultimately contributes to impaired contractile function in the aging heart. Exercise training has been shown to mitigate and even reverse many aspects of the aging process in the heart. However, little is known about the effects of endurance exercise training on cardiac levels of calpain I, calpain II, or calpastatin in senescent hearts. To address this question, we conducted a 3‐month endurance treadmill training study in aged rats. Exercise capacity (as measured by time to exhaustion, EX‐TIME) and VO2max were measured in 22 month old rats and then animals were divided into Sedentary (SED) vs. Exercise (EX) groups. EX animals were trained 5 days a week for 3 months, with speed and duration gradually increased to the point that animals were running at 14 m/min for 45 min. At the end of the 3‐month training period, exercise capacity and VO2max were again measured in all animals. Mean EX‐TIME and VO2max values significantly (p <0.05) declined in SED animals from Pre‐training (PRE) to Post‐training (POST). EX‐TIME declined by 58% in POST compared to PRE, while VO2max declined by 21% in POST vs. PRE. In the EX animals there were significant (p <0.05) increases in EX‐TIME (POST values 172% of PRE) and VO2max (POST values 141% of PRE). To assess cardiac function, echocardiography was used to measure Ejection Fraction (EF%) and Fractional Shortening (FS%). EX training significantly (p <0.05) improved EF% and FS% compared to SED animals (EF% was 36% greater in EX compared to SED; FS% was 26% higher in EX compared to SED). Following sacrifice, rat hearts were quickly excised, and the left ventricle was dissected and flash frozen for Western blot analysis. Endurance exercise training was associated with decreased calpain to calpastatin ratios in aged hearts compared to sedentary counterparts (p <0.05). There was no significant difference in calpain II levels between EX and SED hearts. The improved calpain/calpastatin ratio exhibited by EX animals appears to be due to a significant decrease in calpain I levels compared to SED animals (p <0.05). These results show that endurance exercise increased cardiac function in senescent rats, and that this increase was associated with a decrease in the ratio of calpain to calpastatin. Changes in the cardiac levels of calpain I appear to underlie the decrease in this ratio. Support or Funding Information Marsh Center for Research in Exercise and Movement, University of Wisconsin‐Madison