Time Course Of Transcription Cascades In Skeletal Muscle Mitochondrial Biogenesis During Acute Exercise And Recovery

Mitochondrial biogenesis can be induced by acute exercise, with the increasing number of mitochondria and the improvement of its functions, which can be considered as one of the main mechanisms that acute exercise can lead stress reaction changes in structures and functions of skeletal muscle. Mitochondrial biogenesis is influenced and regulated by both nuclear gene and mitochondrial gene. As a result, it is difficult to study the coordination between nuclear and mitochondrial, as well as the complexity of mitochondrial biogenesis. The transcription cascades in mitochondrial biogenesis show us that co-activators, such as PGC-1α/β, can coactivate transcription factors, such as NRF-1/2, which can activate the nuclear-cod ing mitochontrial gene sequences, such as Tfam and TFBMs. What’s more, after the ingration of PGC-1and NRF-1, both of them can coordinate the promoter of Tfam, the latter one then can directly regulate the transcription and replication of mitochondrial gene, and induce mitochondrial biogenesis.It is generally considered that like PGC-1α, PGC-1p is mainly expressed in mitochondria-rich parts, and has the similar structure as PGC-1α, but they make use of different nuclear receptors. Although PGC-1β can not directly guide the expression of NRF-1, it can combine with NRF-1and act as the coactivator of target gene of NRF-1, as a result increase the expression of mtDNA. Both in vitro and in vivo, PGC-1β can measure the synthesis and metabolism of mitochondria, then enhance mitochondrial biogenesis; All of Tfam, TFB1M and TFB2M are the key targets to regulate both the amount of mtDNA and the related pathway of transcription and replication, as well as to adjust the expression of mtDNA-coding mitochondrial metabolism-related factors, in order to boost mitochondrial biogenesis. Thus, physical movement can induce the expression and the changes in protein of Tfam, TFB1M and TFB2M, while PGC-1famliy can play the key roll in the body’s stress reaction to acute exercise. So far, it is proved that long-term regulated exercise can lead to mitochondrial biogenesis, which is related to the adaptive activation in the pathway of PGC-1transcription cascades. Mitochondria have enduring and dynasmic changes of structure and non-periodic replication and transcription, all of them mentioned above suggest that during acute exercise and recovery period, mitochondrial biogenesis may face a drastic alteration of energy between supply and demand, and have high sensitivity of time course. But there is few study can improve that transcription cascades of PGC-1are possibly included in this course that need to be researched in the future.Objective:To discuss the effects of acute exercise and recovery on time course of transcription cascades of PGC-1β, Tfam and TFBMs in mice’s skeletal muscle, and then from the view of gene transcription, to discuss the impact of acute exercise on skeletal muscle mitochondrial biogenesis.Methods:After three-day’s adaptive training,80male ICR mice were randomly divided into control (A), acute exercise (B) and recovery (C) groups. According to difference of both exercise endure time and recovery time, mice in B and C groups were divided into9groups, including B45、B90、B120、B150and C3、C6、C12、 C18、C24,respectively, n=8. Mice in B and C groups were treated with treadmill exercise at Incremental load, remaining45min、90min、120min and150min in B groups and150min in C groups. After each training mice in B groups were killed immediately and mice in C group were killed after3h、6h、12h、18h and24h, respectively. Their sketetal muscle was extracted, then the extraction of total RNA was used to detect the mRNA expresstion of PGC-1β, Tfam, TFB1M and TFB2M gene; and the extraction of sketetal muscle mitochondria to the level of NO and NOS.Results:(1) Compared with A group, the content of mice’s skeletal muscle mitochondrial NO in B group was significantly increase from B45, reached the peak at B90and then significantly decreased from C18; While the activity of NOS reached the minimum at C3and significantly increased from C18.(2) There was no significant difference in the mRNA expression of mice’s skeletal muscle PGC1-β between A and B group, as same as that between A and C group; But the expressions at B120, B150and C18were significantly increase compared with A. (3) Compared with A group, the mRNA expressions of mice’s skeletal muscle Tfam、 TFB1M and TFB2M in B group was significantly increase at B45and then decrease with the endurance of exercise; The mRNA expression of Tfam was significantly decrease from B120and reached the minimum at C6, peak at C18in recovery group, while TFB1M reached the peak at B45and TFB2M reached the minimum at B150; In recovery group, the mRNA expressions of TFB1M and TFB2M in total were decrease with the endurance of recovery, but there were temporary significant increases at C12.Conclusion:(1) During acute exercise, the content of mitochodrialNO was increase, but that of NOS activity wasn’t significantly increase; In recovery stage, the content of NO fell back to resting state, while NOS activity was gradually increase. What is mentioned above suggest that NO may originate out of mitochondria (there is much possibility for mitochondria to arise oxidative damage). Also, the gradual increase ofNOS activity during recovery stage may be one promoting signal, which demonstrate that mitochondrial endogenous NO can induce mitochondrial biogenesis after exercise.(2) The mRNA expression of Tfam, TFB1M and TFB2M were rapidly up-regulated at the first time of acute exercise, and were down-regulated to varying degrees. While the up-regulation of PGC-1βwas delayed until the end of exercise, when its mRNA expression reached the peak, and then during recovery stage it kept up-regulating, indicating that acute exercise can immediately promote transcriptional signal of mitochondrial biogenesis,as well as Tfam, TFB1M and TFB2M were sensitive to exercise-induced changes of energy demand. Although PGC-1β responsed slowly to exercise, it can play the transcriptional coactivating role in mitochondrial biogenesis after physical movements.