Short-term heat stress causes altered intracellular signaling in oxidative skeletal muscle1

Heat stress (HS) causes morbidities and mortalities, in part by inducing organ-specific injury and dysfunction. Further, HS markedly reduces farm animal productivity, and this is especially true for lean tissue accretion. The purpose of this investigation was to determine the extent to which short-term HS caused muscle dysfunction in skeletal muscle. We have previously found increased free radical injury in skeletal muscle following 24 h of HS. Thus, we hypothesized that HS would lead to apoptosis, autophagy, and decreased mitochondrial content in skeletal muscle. To test this hypothesis, crossbred gilts were divided into 3 groups (n = 8/group): thermal neutral (TN: 21°C), HS (37°C), and pair-fed thermal neutral (PFTN: feed intake matched with heat-stressed animals). Following 12 h of treatment, animals were euthanized and red (STR) and white (STW) portions of the semitendinosus were recovered. Heat stress did not alter intracellular signaling in STW. In STR, the oxidative stress marker malondialdehyde protein and concentration were increased in HS (P = 0.007) compared to TN and PFTN, which was matched by an inadequate antioxidant response, including an increase in superoxide dismutase (SOD) I (P = 0.03) and II relative protein abundance (P = 0.008) and total SOD activity (P = 0.02) but a reduction (P = 0.006) in catalase activity in HS compared to TN. Further, B-cell lymphoma 2–associated X protein (P = 0.02) and apoptotic protease activating factor 1 (P = 0.01) proteins were increased by HS compared to TN and PFTN. However, caspase 3 activity was similar between groups, indicating a lack of apoptotic execution. Despite increased initiation, autophagy appeared to be inhibited by HS as the microtubule-associated protein A/B light chain 3 II/I ratio and mitofusin-2 proteins were decreased (p < 0.03) and sequestosome 1(p62) protein abundance was increased (P = 0.001) in HS compared to TN and PFTN. Markers of mitochondrial content cytochrome c, cytochrome c oxidase IV, voltage-dependent anion channel, pyruvate dehydrogenase, and prohibitins 1 were increased (P < 0.05) in HS compared to TN, whereas mitochondrial biogenesis and mitophagy markers were similar between groups. These data demonstrate that HS caused aberrant intracellular signaling, which may contribute to HS-mediated muscle dysfunction.