Characterization of zebrafish (Danio rerio) muscle ankyrin repeat proteins reveals their conserved response to endurance exercise

Abstract

Muscle proteins with ankyrin repeats (MARPs) ANKRD1 and ANKRD2 are titin-associated proteins with a putative role as transcriptional co-regulators in striated muscle, involved in the cellular response to mechanical, oxidative and metabolic stress. Since many aspects of the biology of MARPs, particularly exact mechanisms of their action, in striated muscle are still elusive, research in this field will benefit from novel animal model system. Here we investigated the MARPs found in zebrafish for protein structure, evolutionary conservation, spatiotemporal expression profiles and response to increased muscle activity. Ankrd1 and Ankrd2 show overall moderate conservation at the protein level, more pronounced in the region of ankyrin repeats, motifs indispensable for their function. The two zebrafish genes, ankrd1a and ankrd1b, counterparts of mammalian ANKRD1/Ankrd1, have different expression profiles during first seven days of development. Mild increase of ankrd1a transcript levels was detected at 72 hpf (1.74±0.24 fold increase relative to 24 hpf time point), while ankrd1b expression was markedly upregulated from 24 hpf onward and peaked at 72 hpf (92.18±36.95 fold increase relative to 24 hpf time point). Spatially, they exhibited non-overlapping expression patterns during skeletal muscle development in trunk (ankrd1a) and tail (ankrd1b) somites. Expression of ankrd2 was barely detectable. Zebrafish MARPs, expressed at a relatively low level in adult striated muscle, were found to be responsive to endurance exercise training consisting of two bouts of 3 hours of forced swimming daily, for five consecutive days. Three hours after the last exercise bout, ankrd1a expression increased in cardiac muscle (6.19±5.05 fold change), while ankrd1b and ankrd2 were upregulated in skeletal muscle (1.97±1.05 and 1.84±0.58 fold change, respectively). This study provides the foundation to establish zebrafish as a novel in vivo model for further investigation of MARPs function in striated muscle.

Longitudinal serum biomarker screening identifies malate dehydrogenase 2 as candidate prognostic biomarker for Duchenne muscular dystrophy

“…Strong correlation with age in DMD patients had previously been described for six of these 30 proteins (CA3, MDH2, MYL3, ETFA, TNNT3, and CK); however, these proteins did not correlate with age in healthy controls, suggesting that these associations are disease specific and not shared by healthy individuals. Most of the proteins showing a negative association with age are known to have a role in muscle contraction (DES, TTN, TNNT2, TNNT3, and MYL3), muscle function (CA3, ANKRD2, and MAP 4), and energy production (CK, MDH2, ETFA, LDHB, and ENO3). The effect of lack of dystrophin on energy production and more specifically on mitochondria are supported by a body of literature showing effects on respiration activity, metabolic dysfunction, and macroautophagy .…”

Towards a personalised approach in exercise-based cardiovascular rehabilitation: How can translational research help? A ‘call to action’ from the Section on Secondary Prevention and Cardiac Rehabilitation of the European Association of Preventive Cardiology

“…177 Beside the classical animal models (mouse and rat) used to analyse the effect of exercise training on molecular and physiological parameters, other species have been used more recently such as drosophila and zebrafish. [178][179][180][181] Exercise training in drosophila results in improvements of physiological and molecular measures, which include enhanced climbing speed, flight performance, aconitase levels and cardiac contractility. Clearly, while the main advantage of using flies as an animal model is that you can train several thousand flies simultaneously, the question of whether and to what extent these findings translate to humans looms large.…”

Swimming exercise as potential measure to improve flesh quality of cultivable fish: A review

“…MARPs in mammals (consisting of Ankrd1/CARP, Ankrd2/ARPP, Ankrd3/DARP) and several lines of evidence strongly confirm that the expression of Ankrd2/ARPP is highly responsible to the muscle plasticity induced by exercise training (Kojic et al, 2011;Miller et al, 2003). The expression of MARP in zebrafish muscle is up-regulated after a relatively short swimming exercise, indicating that it can enhance the activity of striated muscle and promote the development of segment (Boskovic et al, 2018).…”

“…In Boskovic et al, 2018). MARPs in mammals (consisting of Ankrd1/CARP, Ankrd2/ARPP, Ankrd3/DARP) and several lines of evidence strongly confirm that the expression of Ankrd2/ARPP is highly responsible to the muscle plasticity induced by exercise training (Kojic et al, 2011;Miller et al, 2003).…”