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.
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References
Bellmann K, Charette SJ, Nadeau PJ, Poirier DJ, Loranger A, Landry J (2010) The mechanism whereby heat shock induces apoptosis depends on the innate sensitivity of cells to stress. Cell Stress Chaperones 15:101–113. https://doi.org/10.1007/s12192-009-0126-9
Broughton BR, Reutens DC, Sobey CG (2009) Apoptotic mechanisms after cerebral ischemia. Stroke 40:e331–e339. https://doi.org/10.1161/STROKEAHA.108.531632
Chen Y, Yu T (2017) Glucocorticoid receptor activation is associated with increased resistance to heat-induced hyperthermia and injury. Acta Physiol (Oxf) 222:e13015. https://doi.org/10.1111/apha.13015
Chiesa ST, Trangmar SJ, Gonzalez-Alonso J (2016) Temperature and blood flow distribution in the human leg during passive heat stress. J Appl Physiol 120:1047–1058. https://doi.org/10.1152/japplphysiol.00965.2015
Crandall CG, Wilson TE, Marving J, Vogelsang TW, Kjaer A, Hesse B, Secher NH (2008) Effects of passive heating on central blood volume and ventricular dimensions in humans. J Physiol 586:293–301. https://doi.org/10.1113/jphysiol.2007.143057
Cvoro A, Dundjerski J, Trajkovic D, Matic G (1998) Heat stress affects the glucocorticoid receptor interaction with heat shock protein Hsp70 in the rat liver. Biochem Mol Biol Int 46:63–70. https://doi.org/10.1080/15216549800203562
Eefting F, Rensing B, Wigman J, Pannekoek WJ, Liu WM, Cramer MJ, Lips DJ, Doevendans PA (2004) Role of apoptosis in reperfusion injury. Cardiovasc Res 61:414–426. https://doi.org/10.1016/j.cardiores.2003.12.023
Fisher GA, Anderson RL, Hahn GM (1986) Glucocorticoid-induced heat resistance in mammalian cells. J Cell Physiol 128:127–132. https://doi.org/10.1002/jcp.1041280119
Flippo KH, Strack S (2017) Mitochondrial dynamics in neuronal injury, development and plasticity. J Cell Sci 130:671–681. https://doi.org/10.1242/jcs.171017
Gu ZT, Wang H, Li L, Liu YS, Deng XB, Huo SF, Yuan FF, Liu ZF, Tong HS, Su L (2014) Heat stress induces apoptosis through transcription-independent p53-mediated mitochondrial pathways in human umbilical vein endothelial cell. Sci Rep 4:4469. https://doi.org/10.1038/srep04469
Islam A, Abraham P, Hapner CD, Andrews-Shigaki B, Deuster P, Chen Y (2013) Heat exposure induces tissue stress in heat-intolerant, but not heat-tolerant, mice. Stress 16:244–253. https://doi.org/10.3109/10253890.2012.696754
Jezek J, Cooper KF, Strich R (2018) Reactive oxygen species and mitochondrial dynamics: the yin and yang of mitochondrial dysfunction and cancer progression. Antioxidants (Basel) 7:13. https://doi.org/10.3390/antiox7010013
Kalogeris T, Baines CP, Krenz M, Korthuis RJ (2012) Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol 298:229–317. https://doi.org/10.1016/B978-0-12-394309-5.00006-7
Kim J, Villarroel JP, Zhang W et al (2016) The responses of tissues from the brain, heart, kidney, and liver to resuscitation following prolonged cardiac arrest by examining mitochondrial respiration in rats. Oxidative Med Cell Longev 2016:7463407–7463407. https://doi.org/10.1155/2016/7463407
Kregel KC (2002) Heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance. J Appl Physiol 92:2177–2186. https://doi.org/10.1152/japplphysiol.01267.2001
Milleron RS, Bratton SB (2006) Heat shock induces apoptosis independently of any known initiator caspase-activating complex. J Biol Chem 281:16991–17000. https://doi.org/10.1074/jbc.M512754200
Porta F, Takala J, Weikert C, Bracht H, Kolarova A, Lauterburg BH, Borotto E, Jakob SM (2006) Effects of prolonged endotoxemia on liver, skeletal muscle and kidney mitochondrial function. Crit Care 10:R118. https://doi.org/10.1186/cc5013
Rakesh V, Stallings JD, Helwig BG, Leon LR, Jackson DA, Reifman J (2013) A 3-D mathematical model to identify organ-specific risks in rats during thermal stress. J Appl Physiol (1985) 115:1822–1837. https://doi.org/10.1152/japplphysiol.00589.2013
Rao RV, Bredesen DE (2004) Misfolded proteins, endoplasmic reticulum stress and neurodegeneration. Curr Opin Cell Biol 16:653–662. https://doi.org/10.1016/j.ceb.2004.09.012
Redza-Dutordoir M, Averill-Bates DA (2016) Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta 1863:2977–2992. https://doi.org/10.1016/j.bbamcr.2016.09.012
Rolfe DF, Brown GC (1997) Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol Rev 77:731–758. https://doi.org/10.1152/physrev.1997.77.3.731
Slimen IB, Najar T, Ghram A et al (2014) Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage. A review. Int J Hyperth 30:513–523. https://doi.org/10.3109/02656736.2014.971446
van Bommel J, Siegemund M, Henny Ch P, Ince C (2008) Heart, kidney, and intestine have different tolerances for anemia. Transl Res 151:110–117. https://doi.org/10.1016/j.trsl.2007.11.001
Yu T, Deuster P, Chen Y (2016) Role of dynamin-related protein 1-mediated mitochondrial fission in resistance of mouse C2C12 myoblasts to heat injury. J Physiol 594:7419–7433. https://doi.org/10.1113/JP272885
Yu T, Ferdjallah I, Elenberg F, Chen SK, Deuster P, Chen Y (2018) Mitochondrial fission contributes to heat-induced oxidative stress in skeletal muscle but not hyperthermia in mice. Life Sci 200:6–14. https://doi.org/10.1016/j.lfs.2018.02.031
Acknowledgments
We thank Jacob Dohl for the technical assistance.
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This work was supported by the Congressionally Directed Medical Research Program Award W81XWH-14-2-0133.
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Chen, Y., Yu, T. Mouse liver is more resistant than skeletal muscle to heat-induced apoptosis. Cell Stress and Chaperones 26, 275–281 (2021). https://doi.org/10.1007/s12192-020-01163-4
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DOI: https://doi.org/10.1007/s12192-020-01163-4