Redox and mTOR-dependent regulation of plasma lamellar calcium influx controls the senescence-associated secretory phenotype.
Akshaya ChandrasekaranMay Y LeeXuexin ZhangShaheen HasanHabben DestaScott A TenenbaumJuan Andres MelendezPublished in: Experimental biology and medicine (Maywood, N.J.) (2020)
Through its ability to evoke responses from cells in a paracrine fashion, the senescence-associated secretory phenotype (SASP) has been linked to numerous age-associated disease pathologies including tumor invasion, cardiovascular dysfunction, neuroinflammation, osteoarthritis, and renal disease. Strategies which limit the amplitude and duration of SASP serve to delay age-related degenerative decline. Here we demonstrate that the SASP regulation is linked to shifts in intracellular Ca2+ homeostasis and strategies which rescue redox-dependent calcium entry including enzymatic H2O2 scavenging, TRP modulation, or mTOR inhibition block SASP and TRPC6 gene expression. As Ca2+ is indispensable for secretion from both secretory and non-secretory cells, it is exciting to speculate that the expression of plasma lamellar TRP channels critical for the maintenance of intracellular Ca2+ homeostasis may be coordinately regulated with the SASP.
Keyphrases
- induced apoptosis
- gene expression
- cell cycle arrest
- dna damage
- poor prognosis
- dna methylation
- oxidative stress
- traumatic brain injury
- rheumatoid arthritis
- endoplasmic reticulum stress
- cell death
- transcription factor
- protein kinase
- reactive oxygen species
- signaling pathway
- nitric oxide
- cognitive impairment
- stress induced
- brain injury
- knee osteoarthritis
- binding protein
- lps induced
- lipopolysaccharide induced
- functional connectivity
- vascular smooth muscle cells