Mouse liver is more resistant than skeletal muscle to heat-induced apoptosis

Abstract

During passive heat stress, shifting of blood flow from the hepato-splanchnic to peripheral regions produces less favorable physiological conditions in the liver than in the skeletal muscle. We were wondering if the two organs differ in susceptibility to heat injury and thus examined the effects of heat shock exposure on apoptotic and heat stress-related markers in the gastrocnemius muscle and liver of mice. During heat exposure, mice had a peak core body temperature of 41.1 ± 0.7 °C. Heat-exposed mice showed higher levels of reactive oxygen species (ROS), cleaved caspases, fragmented DNA, and Drp1 protein expression in the gastrocnemius muscles than control mice. These changes were not observed in the livers of heat-exposed mice. Furthermore, the levels of glucocorticoid receptor, HSP70, and HSF1 proteins were significantly elevated in the gastrocnemius muscles of heat-exposed mice compared with that of control mice. The livers of heat-exposed mice also revealed increased expression of HSP70 but no changes in the other proteins. These results demonstrate that heat exposure induces significantly lower levels of the stress response and apoptosis in the liver than in the skeletal muscle of mice. The liver tissue resistance against heat stress is associated with low levels of heat-induced ROS production and mitochondrial fission protein expression.

Keywords: DNM1L; Heat tolerance; Hepatic ischemia; Hyperthermia; Mitochondrial dynamics.

Fig. 1

Representative images and quantitative analysis of dihydroethidium (DHE) imaging showing reactive oxygen species (ROS) formation in gastrocnemius muscle (a) and liver (b) tissues of heat-exposed (heat) and unexposed mice (control). RLU, relative light units. Results are described as mean ± SD, n = 6 mice per group, *p < 0.001 versus control

Fig. 2

Representative images and quantitative analysis of activated caspase 3/7 in gastrocnemius muscle (a) and liver (b) tissues of heat-exposed (heat) and unexposed mice (control). Statistics show quantification of caspase 3/7 activity per visual field (20 fields each animal). RLU, relative light units. Results are described as mean ± SD, n = 6 mice per group, *p < 0.001 versus control

Fig. 3

Representative images and quantitative analysis of TUNEL staining in gastrocnemius muscle (a) and liver (b) tissues of heat-exposed (heat) and unexposed mice (control). Statistics show the quantification of TUNEL-positive nuclei per visual field (20 fields each animal). RLU, relative light units. Results are described as mean ± SD, n = 6 mice per group, *p < 0.001 versus control

Fig. 4

Representative Western blot and quantitative analysis of GR, HSP70, HSF1, and Drp1 proteins in gastrocnemius muscle (a) and liver (b) tissues of heat-exposed (heat) and unexposed mice (control). Results are described as mean ± SD, n = 6 mice per group, *p < 0.001 versus control