Browsing by Author "Ganesan, Shanthi"
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- Acute heat stress activated inflammatory signaling in porcine oxidative skeletal muscleGanesan, Shanthi; Volodina, Olga; Pearce, Sarah C.; Gabler, Nicholas K.; Baumgard, Lance H.; Rhoads, Robert P.; Selsby, Joshua T. (2017-08)Despite well-studied clinical manifestations, intracellular mechanisms of prolonged hyperthermic injury remain unclear, especially in skeletal muscle. Given muscle's large potential to impact systemic inflammation and metabolism, the response of muscle cells to heat-mediated injury warrants further investigation. We have previously reported increased activation of NF-κB signaling and increased NF-κB and AP-1-driven transcripts in oxidative skeletal muscle following 12 h of heat stress. The purpose of this investigation was to examine early heat stress-induced inflammatory signaling in skeletal muscle. We hypothesized that heat stress would increase NF-κB and AP-1 signaling in oxidative skeletal muscle. To address this hypothesis, 32 gilts were randomly assigned to one of four treatment groups (n = 8/group): control (0 h: 21°C) or exposed to heat stress conditions (37°C) for 2 h (n = 8), 4 h (n = 8), or 6 h (n = 8). Immediately following environmental exposure pigs were euthanized and the red portion of the semitendinosus muscle (STR) was harvested. We found evidence of NF-κB pathway activation as indicated by increased protein abundance of NF-κB activator IKK-α following 4 h and increased total NF-κB protein abundance following 6 h of heat stress. Heat stress also stimulated AP-1 signaling as AP-1 protein abundance was increased in nuclear fractions following 4 h of heat stress. Interleukin-6 protein abundance and activation of the JAK/STAT pathway were decreased in heat stressed muscle. These data indicate that heat stress activated inflammatory signaling in the porcine STR muscle via the AP-1 pathway and early activation of the NF-κB pathway.
- Heat stress causes dysfunctional autophagy in oxidative skeletal muscleBrownstein, Alexandra J.; Ganesan, Shanthi; Summers, Corey M.; Pearce, Sarah C.; Hale, Benjamin J.; Ross, Jason W.; Gabler, Nicholas K.; Seibert, Jacob T.; Rhoads, Robert P.; Baumgard, Lance H.; Selsby, Joshua T. (The Physiological Society, 2017-06)We have previously established that 24h of environmental hyperthermia causes oxidative stress and have implicated mitochondria as likely contributors to this process. Given this, we hypothesized that heat stress would lead to increased autophagy/mitophagy and a reduction in mitochondrial content. To address this hypothesis pigs were housed in thermoneutral (TN; 20 degrees C) or heat stress (35 degrees C) conditions for 1- (HS1) or 3- (HS3) days and the red and white portions of the semitendinosus collected. We did not detect differences in glycolytic muscle. Counter to our hypothesis, upstream activation of autophagy was largely similar between groups as were markers of autophagosome nucleation and elongation. LC3A/B-I increased 1.6-fold in HS1 and HS3 compared to TN (P < 0.05), LC3A/B-II was increased 4.1-fold in HS1 and 4.8-fold in HS3 relative to TN, (P < 0.05) and the LC3A/B-II/I ratio was increased 3-fold in HS1 and HS3 compared to TN suggesting an accumulation of autophagosomes. p62 was dramatically increased in HS1 and HS3 compared to TN. Heat stress decreased mitophagy markers PINK1 7.0-fold in HS1 (P < 0.05) and numerically by 2.4-fold in HS3 compared to TN and BNIP3L/NIX by 2.5-fold (P < 0.05) in HS1 and HS3. Markers of mitochondrial content were largely increased without activation of PGC-1 signaling. In total, these data suggest heat-stress-mediated suppression of activation of autophagy and autophagosomal degradation, which may enable the persistence of damaged mitochondria in muscle cells and promote a dysfunctional intracellular environment.
- Short-term heat stress alters redox balance in porcine skeletal muscleVolodina, Olga; Ganesan, Shanthi; Pearce, Sarah C.; Gabler, Nicholas K.; Baumgard, Lance H.; Rhoads, Robert P.; Selsby, Joshua T. (The Physiological Society, 2017-04)Heat stress contributes to higher morbidity and mortality in humans and animals and is an agricultural economic challenge because it reduces livestock productivity. Redox balance and associated mitochondrial responses appear to play a central role in heat stress-induced skeletal muscle pathology. We have previously reported increased oxidative stress and mitochondrial content in oxidative muscle following 12h of heat stress. The purposes of this investigation were to characterize heat stress-induced oxidative stress and changes in mitochondrial content and biogenic signaling in oxidative skeletal muscle. Crossbred gilts were randomly assigned to either thermal neutral (21 degrees C; n=8, control group) or heat stress (37 degrees C) conditions for 2h (n=8), 4h (n=8), or 6h (n=8). At the end, their respective environmental exposure, the red portion of the semitendinosus muscle (STR) was harvested. Heat stress increased concentration of malondialdehyde (MDA) following 2 and 4h compared to thermal neutral and 6h, which was similar to thermal neutral, and decreased linearly with time. Protein carbonyl content was not influenced by environment. Catalase activity was increased following 4h of heat stress and superoxide dismutase activity was decreased following 6h of heat stress compared to thermal neutral conditions. Heat stress-mediated changes in antioxidant activity were independent of altered protein abundance or transcript expression. Mitochondrial content and mitochondrial biogenic signaling were similar between groups. These data demonstrate that heat stress caused a transient increase in oxidative stress that was countered by a compensatory change in catalase activity. These findings contribute to our growing understanding of the chronology of heat stress-induced intracellular dysfunctions in skeletal muscle.