Acute Heat Exposure Alters Autophagy Signaling in C2C12 Myotubes

Abstract

Autophagy is a major intracellular degradation process that is essential for the clearance of unnecessary proteins/organelles and the maintenance of cellular homeostasis. The inhibition of autophagy results in cellular consequences associated with many skeletal muscle pathologies, and therapies designed to elevate autophagic activity may provide protection from such pathologies. Acute exposure to low levels of heat has therapeutic effects; however, the impact of heat on skeletal muscle autophagy remains unclear. In the present study, C2C12 myotubes were maintained at 37 • C thermoneutral (TN) or heated at 40 • C heat treatment (HT) for 1 h. Myotubes were harvested immediately after heating, or returned to 37 • C for recovery of 2 or 24 h. HT resulted in an elevation in pAMPK (T172), Beclin-1, and LC3 II, a marker for autophagosome formation, but no change in p62. In the context of autophagy inhibition with Bafilomycin A1, HT resulted in lower LC3 II compared to TN. The applied heat load induced the heat shock response, as evidenced by immediate upregulation of HSF1 and Hsp70. Hsp70 continued to increase during recovery, whereas pHsp27 was downregulated acutely in response to HT, but retuned to TN levels by 2 h of recovery. HT also reduced the phosphorylation of the MAP-kinases p38 and JNK. These findings suggest that an acute, short bout of mild heat may be beneficial to skeletal muscle by increasing AMPK activity, markers of autophagasome formation, and the heat shock response.

An Integrative Bioorthogonal Nanoengineering Strategy for Dynamically Constructing Heterogenous Tumor Spheroids

“…Mitochondria are therefore activated and improve ATP production and respiratory coupling efficiency, mainly due to the increasing of AMP‐activated protein kinase (AMPK) activity. [ 49 ] As a result, high mitochondrial activity is often observed in cells undergoing dynamic culture conditions. Meanwhile, western blot data also show that the protein levels of PCNA and Ki67, standard markers of cell proliferation, [ 50 ] increased in PDC group (Figure 4M and Figure S14, Supporting Information), suggesting that dynamic photothermal culture can increase cell metabolism to promote tumor spheroid growth.…”

Strategies for the Management of Spike Protein-Related Pathology

“…Spermidine, a polyanion compound found in high concentrations in wheat germ [ 175 ], can potently stimulate autophagy [ 176 ]. Other factors which influence autophagy are acute heat exposure, as one would experience in a sauna [ 177 , 178 ], flavonoid consumption [ 179 ], phenolic compounds [ 180 , 181 ], and coffee [ 182 ]. Resveratrol can also induce fasting, as it acts as a protein restriction mimetic [ 183 ], and metformin, a diabetes medication, can influence autophagy signaling [ 184 ].…”

Strategies for the Management of Spike Protein-Related Pathology

“…Spermidine, a polyanion compound found in high concentrations in wheat germ 126 , can potently stimulate autophagy 127 . Other factors which influence autophagy are acute heat exposure, as one would experience in a sauna 128,129 , flavonoid consumption 130 , phenolic compounds 131,132 , and coffee 133 . Resveratrol can also induce fasting, as it acts as a protein restriction mimetic 134 , and metformin, a diabetes medication, can influence autophagy signalling 135 .…”