Succinate promotes skeletal muscle protein synthesis via Erk1/2 signaling pathway
Authors: Qingyan Jiang
Yaqiong Xu
Bingqing Liang
Canjun Zhu
Xiaotong Zhu
Songbo Wang
Ping Gao
Gang Shu
Yexian Yuan
Jingren Xu
Xingcai Cai
Lina Wang
Yongliang Zhang
Xiuqi Wang
Journal: Molecular Medicine Reports (2017)
Discipline: CLINICAL MEDICINE
Keywords: Endurance training; Succinate; Protein synthesis; Skeletal muscle; AKT
Affiliations: Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong 510642, P.R. China.

Abstract:  It is well known that endurance training is effective to attenuate skeletal muscle atrophy. Succinate is a typical TCA metabolite, of which exercise could dramatically increase the content. The present study aimed to investigate the effect of succinate on protein synthesis in skeletal muscle, and try to delineate the underlying mechanism. The in vitro study revealed that succinate dose‑dependently increased protein synthesis in C2C12 myotube along with the enhancement of phosphorylation levels of AKT Serine/Threonine Kinase 1(Akt), mammalian target of rapamycin, S6, eukaryotic translation initiation factor 4E, 4E binding protein 1 and forkhead box O (FoxO) 3a. Furthermore, it was demonstrated that 20 mM succinate markedly increased [Ca2+]i. Then, the phospho‑extracellular regulated kinase (Erk), ‑Akt level and the crosstalk between Erk and Akt were elevated in response to succinate. Notably, the Erk antagonist (U0126) or mTOR inhibitor (rapamycin) abolished the effect of succinate on protein synthesis. The in vivo study verified that succinate dose‑dependently increased the protein synthesis, in addition to phosphorylation levels of Erk, Akt and FoxO3a in gastrocnemius muscle. In summary, these findings demonstrated that succinate promoted skeletal muscle protein deposition via Erk/Akt signaling pathway. 

Retracted: No

PubPeer comments:
  In this study, 37 pairs of specimens were selected from surgically treated BCa cases, and BCa tissues and their corresponding adjacent tissues were collected and then stored at -80u00b0C. The collection of clinical specimens was approved by the Ethics Monitoring Committee . **Which** ethics committee? The authors are spread across two hospitals, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai; and the Ninth Peopleu2019s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai. The lack of detail about where the putative patients were recruited, and the source of the ethics approval, does not foster confidence in their existence. ------------------------------------------------------------------------- Figs 1D and 3C.  Kaplan Meier survival curve of bladder cancer patients based on HOXA10 expression; the prognosis of patients with high expression was significantly worse than that of low expression group ...  Kaplan Meier survival curve of bladder cancer patients based on FOSL1 expression was shown; the prognosis of patients with low expression was significantly worse than that of high expression group . ![file] It is clear that when the 37 bladder-cancer cases are dichotomised by high- or low-expression of HOXA10, the total survival for the group is much lower than when they are dichotomised by high- or low-FOSL1 expression, so the latter is better from the perspective of patients. 1D is another manifestation of  Hoya s Law for J.BUOn ERMPS :  When 40 or 50 cases of any given cancer are dichotomised into half-groups of high- or low-expression of any given noncoding RNA, survival rate for one half-group or both *always* drops to 0% at 75 months. Some other examples, from left to right: - Fig 1 from [Zang et al (2020)] - Fig 1 from [Li et al (2020)] - Fig 1, and Fig 4D, from [Cui et al (2019)] - Fig 1D from [Gao et al (2019)] . ![file] *[left]* Figure 1C from [Wu et al (2020)] . *[right]* Figs 1D, 3E from [Wu et al (2019)] . ![file] 1D from [Luo, Yan Liu] : ![] ,