Journal of Jilin University(Medicine Edition) ›› 2021, Vol. 47 ›› Issue (4): 849-856.doi: 10.13481/j.1671-587X.20210405

• Research in basic medicine • Previous Articles     Next Articles

Effect of asparagine synthetase on reduction of skeletal muscle in APP/PS1 mice transplanted with melanoma

Ying DONG1,Hang LYU1,Jianv GUO1,2,3,Hong ZHENG1,2,3,Dan GUO1,Like WANG1,Dan WANG1,Changjie CHEN2,Liankun SUN3,Yong ZHANG3,Chunyan YU1()   

  1. 1.Department of Pathology,College of Basic Medical Sciences,Beihua University,Jilin 132013,China
    2.Department of Laboratory,Affiliated Hospital,Beihua University,Jilin 132013,China
    3.Department of Pathophysiology,School of Basic Medical Sciences,Jilin University,Changchun 130021,China
  • Received:2020-12-11 Online:2021-07-28 Published:2021-07-22
  • Contact: Chunyan YU E-mail:gchunyanyu@163.com

Abstract: Objective

To investigate the role of asparagine synthetase(ASNS) on reduction of skeletal muscle in the amyloid precursor protein/presenilin 1(APP/PS1) mice transplanted with melanoma,and to clarify its mechanism.

Methods

The C57BL/6J(C57) and APP/PS1 mice were transplarted with melanoma cells (C57 transplanted tumor group and APP/PS1 transplanted tumor group),at the same time, C57 control group and APP/PS1 control group were set up.The mass of gastrocnemius was measured and the sarcopenia index (SI) was calculated with the gastrocnemius mass to body weight ratio.The morphology of gastrocnemius tissue of the mice was determined by HE staining. The mRNA expression levels of muscle specific atrophy gene E3 ubiquitin protein ligase 1 (Atrogin-1),muscle ring finger protein 1(MuRF1) and ASNS in gastrocnemius tissue of the mice were measured by Real-time fluorescence quantitative PCR(RT-qPCR). The expression levels of ASNS and endoplasmic stress related glucose regulated protein 78(GRP78),activating transcription factor-4(ATF4),eukaryotic cell initiation factor 2α(eIF2α),phosphorylated eIF2α(p-eIF2α) in gastrocnemius tissue of the mice were measured by Western blotting method.

Results

Compared with C57 control group, the SI of the mice in C57 transplanted tumor group was decreased (P<0.05),gastrocnemius cells had hyaline degeneration,the sarcoplasm was stained blue, and some muscle fiber showed intranuclear migration; the expression levels of Atrogin-1,MuRF1 and ASNS mRNA in gastrocnemius tissue of the mice were increased (P<0.05), and the expression level of ASNS protein was increased (P<0.05);the expression levels of GRP78 and ATF4 and the ratio of p-eIF2α/eIF2α were increased(P<0.05).Compared with APP/PS1 control group,the SI of the mice in APP/PS1 transplanted tumor group was decreased (P<0.05), some muscle fibers of gastrocnemius were swelling, and some were thin; intranuclear migration was easily seen, and the sarcoplasm was red; the expression levels of Atrogin-1,MuRF1 and ASNS mRNA in gastrocnemius tissue were increased (P<0.05),and the expression level of ASNS protein was increased (P<0.05);the expression levels of GPR78 and ATF4 proteins and the ratio of p-eIF2α/eIF2α were increased(P<0.05).Compared with C57 transplanted tumor group,the SI of the mice in APP/PS1 transplanted tumor group was decreased (P<0.05),the level of Atrogin-1 mRNA was increased (P<0.05),and the level of ASNS mRNA in gastrocnemius tissue was decreased (P<0.05); there was no difference in the expression level of ASNS protein(P>0.05);the expression levels of GRP78 and ATF4 proteins and the ratio of p-eIF2α/eIF2α were decreased (P<0.05).

Conclusion

Gastrocnemius in the APP/PS1 transplanted melanoma mice is more prone to reduction of skeletal muscle, and its mechanism may be associated with the reduced levels of adaptive response in ASNS transcription, and endoplasmic reticulum stress in PERK-eIF2a-ATF4 signaling pathway may be involved in the regulation of ASNS transcriptional activity.

Key words: asparagine synthetase, reduction of skeletal muscle, amyloid precursor protein/presenilin 1, transplanted tumor, melanoma B16 cells

CLC Number: 

  • R739.5