GINGEROL DISCHARGES NG115-401L NEURAL CELL Ca2+ STORES, ACTIVATES Ca2+ INFLUX AND PROMOTES CELL DEATH
Introduction/Abstract
6-gingerol, the main bioactive component of ginger, exhibits various therapeutic effects via its Ca2+ mobilizing effect. However, the underlying mechanism is elusive.
Purpose
To test gingerol’s effect on cytosolic free Ca2+ ([Ca2+]i) and sarco/endoplasmic reticulum Ca2+- ATPase (SERCA) activity on sarcoplasmic reticulum (SR) microsomes and NG115-401L, a neural cell line with diminished level of stromal interacting molecule 1 (STIM1) and deficient endoplasmic reticulum (ER)- regulated Ca2+ signaling pathways.
Method
Cells were loaded with the Ca2+ probe Fura-2 to detect [Ca2+]i changes, and Ca2+-ATPase enzymatic activity were measured by the coupled enzyme assay of NADH oxidation in skeletal muscle SR microsomes.
Results
Gingerol stimulates an approximately two-fold increase in ATP hydrolysis in skeletal muscle SR microsomes. Moreover, gingerol incubation nearly completely reverses SERCA enzymatic function against SERCA blocker cyclopiazonic acid (CPA). However, in NG115-401L cells, gingerol fails to enhance ER Ca2+ uptake, but induces a transient [Ca2+]i elevation in the absence of external Ca2+ much like thapsigargin (TG) and CPA. Additionally, gingerol is unable to protect 401L cells against CPA-induced apoptosis, confirming that the compound has no ER Ca2+ enhancing effect in 401L cells. Surprisingly, gingerol’s apparent ER Ca2+ depleting action couples to long-lived Ca2+ influx pathways, whereas those of TG and CPA do not.
Significance
These results argue for a finer regulatory control on SERCA function with gingerol actions revealing potentially novel routes of coupling altered pump regulation to the assembly of functional Ca2+ influx units.
Location
DeRosa University Center, Stockton campus, University of the Pacific
Format
Poster Presentation
GINGEROL DISCHARGES NG115-401L NEURAL CELL Ca2+ STORES, ACTIVATES Ca2+ INFLUX AND PROMOTES CELL DEATH
DeRosa University Center, Stockton campus, University of the Pacific
6-gingerol, the main bioactive component of ginger, exhibits various therapeutic effects via its Ca2+ mobilizing effect. However, the underlying mechanism is elusive.
