Gene interactions and pathways from curated databases and text-mining
Arterioscler Thromb Vasc Biol 2011, PMID: 21415389

mTOR complex 2 activation by reconstituted high-density lipoprotein prevents senescence in circulating angiogenic cells.

Guo, Xianrong; Yu, Miao; Kang, Xiaomin; Yin, Hongchao

OBJECTIVE

Circulating angiogenic cells (CACs) participate in neovascularization and arterial repair. Although high-density lipoprotein (HDL) is known to enhance the functional activity of CACs, the mechanisms underlying this regulation are poorly understood. Here, we examined the mechanism(s) by which reconstituted HDL (rHDL) affects CAC senescence.

RESULTS

CACs isolated from human peripheral blood and treated with rHDL displayed reduced senescence, as measured by acidic β-galactosidase staining. This protective effect was blocked by the mammalian target of rapamycin (mTOR) inhibitor (rapamycin). According to Western blot analysis and immunoprecipitation results, rHDL promoted mTOR phosphorylation, mTOR-rictor complex formation, and mTOR-rictor-dependent Akt activation, which were accompanied by increased nuclear translocation of human telomerase reverse transcriptase and enhanced nuclear telomerase activity. Suppression of rictor gene expression with a small interfering RNA blocked mTOR-rictor complex formation and Akt activation. The suppression also abolished the rHDL-induced inhibition of CAC senescence and promotion of nuclear telomerase activity. Treatment of aged mice with rHDL attenuated spleen-derived CAC senescence. In CACs isolated from rHDL-treated aged mice, the phosphorylated mTOR and Akt levels were significantly enhanced.

CONCLUSIONS

rHDL stimulates sustained mTOR phosphorylation and mTOR-rictor complex formation and inhibits senescence onset in CACs through mTOR complex 2 pathway activation.

Document information provided by NCBI PubMed

Text Mining Data

Akt → mTOR-rictor: " According to Western blot analysis and immunoprecipitation results, rHDL promoted mTOR phosphorylation, mTOR-rictor complex formation, and mTOR-rictor dependent Akt activation, which were accompanied by increased nuclear translocation of human telomerase reverse transcriptase and enhanced nuclear telomerase activity "

mTOR → mTOR-rictor: " According to Western blot analysis and immunoprecipitation results, rHDL promoted mTOR phosphorylation, mTOR-rictor complex formation, and mTOR-rictor dependent Akt activation , which were accompanied by increased nuclear translocation of human telomerase reverse transcriptase and enhanced nuclear telomerase activity "

Manually curated Databases

No curated data.