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Investigating the activity and role of store operated calcium entry (SOCE) in a cellular model of senescence

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Seshadri, V and Azimi, I, Investigating the activity and role of store operated calcium entry (SOCE) in a cellular model of senescence, Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting, 29 November - 2 December 2021, Online Web Conference (2021) [Conference Extract]


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Abstract

Introduction: Calcium (Ca2+) homeostasis dysregulation has been linked to many age-related diseases such as Alzheimer's, Parkinsons disease, Huntington's disease and many more. SOCE is one of the major pathways involved in the regulation of Ca2+ homeostasis intracellularly. Human derived fibroblasts (HDFs) have limited replicative capacity known as the Hayflick limit after which cells undergo growth arrest known as replicative senescence. Aims. To study the activity of SOCE in cellular ageing and the effect of pharmacological modulation of SOCE on cellular senescence.

Methods: The activity of SOCE in young and aged HDFs was assessed in calcium influx assays using Fluo-4 calcium indicator. To understand the effect of SOCE modulation on cellular senescence, HDFs were treated with DMSO control or SOCE agonist, IA65 (1, 3 and 10 然), or SOCE inhibitor, Synta-66 (1 and 10 然) and cells were passaged at fixed time interval of four and three days. Cumulative population doublings (CPD) were calculated at each passage until the cells reached the plateau phase of cell growth (Passage 38).

Results: Calcium influx assays demonstrated that SOCE pathway is active in the HDFs and can be regulated by its pharmacological modulators, IA65 and Synta-66. In addition, HDFs treated with IA65 at 3 然 concentration showed a delayed plateauing of the CPD curve compared to the other treatment groups.

Discussion: SOCE is present in HDF and can be modulated using IA65 and Synta-66. Preliminary data shows that there is a modest effect of SOCE activator, IA65 at 3 然, on delaying the onset of replication arrest, however further investigation is needed to confirm the effect of the drug on delaying cellular senescence. Given the implication of cellular senescence in various pathological conditions, identification of novel therapeutic targets against cellular senescence, may pave the way to treatment of these conditions.

Item Details

Item Type:Conference Extract
Keywords:store operated calcium entry, senescence
Research Division:Biomedical and Clinical Sciences
Research Group:Pharmacology and pharmaceutical sciences
Research Field:Basic pharmacology
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the health sciences
UTAS Author:Azimi, I (Dr Iman Azimi)
ID Code:151416
Year Published:2021
Deposited By:Pharmacy
Deposited On:2022-07-28
Last Modified:2022-07-28
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