I am looking to activate autophagy under autophagic inhibition conditions, by supplementing cells with extracellular calcium source, which can activate calmodulin and intern activate autophagy, cell survival and proliferation!
Hi Gaurav, extracellular Ca²⁺ can activate calmodulin, but only if it enters the cell via Ca²⁺ channels. This may trigger autophagy through the CaMKKβ–AMPK pathway, although its effects can be context-dependent. Ensure that your calcium source actually increases intracellular Ca²⁺ (e.g., CaCl₂ plus an ionophore), and then verify the autophagy markers.
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Hi Gaurav,
The question is how autophagy is being inhibited. If the inhibition is achieved by blocking calcium channels or preventing calcium influx, then reintroducing extracellular calcium replenishes these critical signals, allowing them to initiate the downstream mechanisms required for autophagosome formation and function. Moreover, the specific cell type, the concentration of calcium added, and the overall cellular context will significantly influence the outcome.
The role of calcium is complex. The overall effect of calcium on autophagy isn't always straightforward. In some instances, calcium can also have anti-autophagic actions, particularly if it interferes with cellular energy status or other essential processes.
Best,
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