Scriptaid/exercise-induced lysine acetylation is another type of posttranslational modification occurring in titin

Abstract

Titin serves important functions in skeletal muscle during exercise, and posttranslational modifications of titin participate in the regulation of titin-based sarcomeric functions. Scriptaid has exercise-like effects through the inhibition of HDAC and regulatory acetylation of proteins. However, it remains mostly unclear if exercise could result in titin’s acetylation and whether Scriptaid could regulate acetylation of titin. We treated C57BL/6 mice with 6-wk treadmill exercise and 6-wk Scriptaid administration to explore Scriptaid’s effects on mice exercise capacity and whether Scriptaid administration/exercise could induce titin’s acetylation modification. An exercise endurance test was conducted to explore their effects on mice exercise capacity, and proteomic studies were conducted with gastrocnemius muscle tissue of mice from different groups to explore titin’s acetylation modification. We found that Scriptaid and exercise did not change titin’s protein expression, but they did induce acetylation modification changes of titin. In total, 333 acetylated lysine sites were identified. Exercise changed the acetylation levels of 33 lysine sites of titin, whereas Scriptaid changed acetylation levels of 31 titin lysine sites. Exercise treatment and Scriptaid administration shared 11 lysine sites. In conclusion, Scriptaid increased exercise endurance of mice by increasing the time mice spent running to fatigue. Acetylation is a common type of posttranslational modification of titin, and exercise/Scriptaid changed the acetylation levels of titin and titin-interacting proteins. Most importantly, titin may be a mediator through which Scriptaid and exercise modulate the properties and functions of exercise-induced skeletal muscle at the molecular level. NEW & NOTEWORTHY Scriptaid administration increased mouse exercise endurance. Acetylation is another type of posttranslational modification of titin. Scriptaid/exercise changed acetylation levels of titin and titin-interacting proteins. Titin may mediate exercise-induced skeletal muscle properties and functions.

Role of Histone Deacetylases in Skeletal Muscle Physiology and Systemic Energy Homeostasis: Implications for Metabolic Diseases and Therapy

“…of C57BL/6 mice (Gaur et al, 2016). One possible explanation of above observation is the potential target of scriptaid inhibition of titin (a structure protein of sarcomere) deacetylation and downstream genes of Class IIa HDACs (Gaur et al, 2016;Huang et al, 2019).…”

Synaptic Protein Phosphorylation Networks Are Associated With Electroacupuncture-Induced Circadian Control in the Suprachiasmatic Nucleus

“…The protein solution was reduced with 5 mM dithiothreitol at 56°C for 30 min, followed by the addition of iodoacetamide to a final concentration of 11 mM and incubation in the dark for 15 min. Subsequently, the protein was digested with trypsin at 1:50 and 1:100, respectively ( Huang et al, 2020 ; Feb 1). The peptide was solubilized in 0.5 M TEAB and labeled according to the TMT kit protocol method.…”

Protein nanomechanics in biological context

“…Modulation of the content of titin isoforms is well documented under several physiological and pathological situations, resulting in changes of the mechanical output of the tissue as in the case of hypertensive cardiomyopathy (Linke and Hamdani 2014). A more rapid adjustment of the mechanical properties of titin can be achieved by post-translational modifications like phosphorylation, acetylation, and oxidation, which in turn can also be influenced by force (Abdellatif et al 2021;Herrero-Galán et al 2020;Herrero-Galán et al 2019;Huang et al 2020;Linke and Hamdani 2014;Loescher et al 2020).…”