The Effects of Antioxidants and Pulsed Magnetic Fields on Slow and Fast Skeletal Muscle Atrophy Induced by Streptozotocin: A Preclinical Study

Figure 1

Multifaceted signaling pathways governing skeletal muscle atrophy and hypertrophy: a systematic overview. The PI3K/Akt/mTOR, extracellular insulin, and insulin-like growth factor-1 pathways are essential for protein synthesis in skeletal muscle. Upon activation, PI3K converts PIP2 to PIP3 with phosphorylation, which activates PDK1, leading to the phosphorylation and activation of Akt. Subsequently, p-Akt phosphorylates and activates mTOR, which induces protein synthesis via subpathways. Akt also phosphorylates and inhibits 4E-BP1, which plays a negative regulatory role in protein synthesis, and activates p70S6K by phosphorylation. FoxOs, when active, upregulate FBXO32 and TRIM63, which are involved in muscle atrophy. Upregulated FBXO32 ubiquitinates and degrades its substrates, and similarly, TRIM63 ubiquitinates and degrades sarcomeric proteins, leading to muscle atrophy. Myostatin inhibits Akt and MyoD, a transcription factor involved in the induction of protein synthesis. TNF-α inhibits NF-κB and downregulates TRIM63. In the case of GLUT4, p-Akt suppresses AS160, which inhibits the translocation of GLUT4 vesicles, facilitating glucose uptake. Lastly, the ubiquitin proteasome system plays a crucial role in protein breakdown via E1, E2, and E3 enzymes. The ZNF216 receptors in the 26S proteasome system recognize Ub proteins and transfer them to the proteasome. Note that in the figure, activation of proteins is depicted by blue arrows, while inhibition is represented by red blunt-tipped arrows.