Effect of HSP25 loss on muscle contractile function and running wheel activity in young and old mice

Abstract

Aging is associated with an adverse decline in muscle function, often manifesting as decreased strength and increased muscle fatigability that negatively affects the overall health of the elderly. Heat shock proteins (HSPs), a family of stress inducible proteins known to protect cells from damage, are highly induced in muscle cells following exercise, but both basal and inducible levels decline with age. Utilizing young and old mice lacking HSP25 (Hsp25−/−) we tested the hypothesis that HSP25 is required to maintain normal muscle function and that age related decreases in HSP25 directly contribute to declining muscle function. Running wheel distances over 14 days for young Hsp25−/− mice were significantly lower than for the corresponding Hsp25+/+ genotype (81238 vs. 33956 AUC, respectively). While older groups both ran significantly less than young groups, in aged mice HSP25 loss did not lead to any additional decrease. Significantly lower myofibrillar (contractile) protein levels in young Hsp25−/− vs. Hsp25+/+ (15.7 ± 0.2 vs. 13.4 ± 0.3 mg/mg muscle) mice suggests HSP25 loss was associated with greater muscle breakdown during voluntary wheel running. In vivo, plantarflexor maximal isometric force was significantly decreased in aged vs. young mice, but the loss of HSP25 had no effect on either group. However, plantarflexor fatigability over 10 contractions was significantly higher in young Hsp25−/− vs. Hsp25+/+ mice (59 ± 3 vs. 49 ± 4% of initial force, respectively) but no similar effect of genotype was detected in the older groups. There was no difference in muscle caspase-3 activity between Hsp25−/− and Hsp25+/+ mice, whether young or old, but there was a significant genotype independent increase in activity with age. Overall, the results suggest that the absence of HSP25 primarily contributes to muscle fatigue resistance, rather than maximal force production, and that this effect is most evident in young compared to older mice.

Functional effects of milk bioactive peptides on skeletal muscle of rats

“…Exercise promotes the HSP70 response (Milne & Noble, 2002;Salo et al, 1991), and this effect is also in agreement with the results of the present study because, independently of the peptide consumed, exercise caused HSP70 upregulation. HSP25 is detectable in unstressed tissue and may elevate its expression as a result of environmental perturbations (Gernold et al, 1993), including exercise (Huey & Meador, 2008;Huey et al, 2013). Our data showed that exercise elevated only the HSP25 expression in the groups that received Leu-Val, whereas the HSP25 expression in the groups that received the other peptides did not differ from that of the control (rest).…”

“…Similarly, the predominant accumulation of HSP25 in muscle tissue is involved in the organization of the intracellular matrix, the preservation of cell structure, stress resistance (Gernold, Knauf, Gaestel, Stahl, & Kloetzel, 1993), the prevention of and protection against oxidative and thermal damage (Musch, Kapil, & Chang, 2004) and the repair of muscle damage (Huey et al, 2013). Mice lacking HSP25 (Hsp25 −/−) run shorter distances, have reduced myofibrillar (contractile) protein levels and develop fatigue more rapidly than the Hsp25+/+ mice, suggesting that HSP25 expression is required to maintain adequate muscle function (Huey et al, 2013). The HSP70 and HSP25 responses both promote stress resistance (Gernold et al, 1993), protect tissues during exercise (Huey & Meador, 2008), and alter homeostasis (Nishizawa et al, 2013).…”

“…Current evidence suggests that the discovery of new HSP inducers could improve several health parameters (Silverstein et al, 2014), including muscle function (Brinkmeier & Ohlendieck, 2014;Huey et al, 2013;Silverstein et al, 2014). Previous studies showed that dietary proteins and supplementation with certain amino acids may influence the HSP response (De Moura et al, 2014;Wischmeyer, 2002).…”

“…HSPs participate in the restoration and/or stabilization of damaged proteins (Cumming, Paulsen, Wernbom, Ugelstad, & Raastad, 2014) thus stimulating higher cell resistance, tolerance and survival (Santoro, 2000). In skeletal muscle, HSPs are involved in the prevention of protein degradation and aggregation, the removal and stabilization of misfolded non-functional muscle proteins, the facilitation of correct folding, the maintenance of muscle integrity (Brinkmeier & Ohlendieck, 2014) and the stimulation of normal muscle function (Huey, Hilliard, & Hunt, 2013).…”

The Invalidation of HspB1 Gene in Mouse Alters the Ultrastructural Phenotype of Muscles

“…g . increased physical activity [ 10 ] [ 11 ] including lifelong training [ 12 ], endurance training [ 13 ], and eccentric exercise [ 14 ]. Some protective functions of Hsp27 are suggested by its translocation from the cytosolic to myofibrillar fraction and binding to cytoskeletal structures such as Z-disk proteins [ 15 ] [ 14 ].…”