Cells that are about to die send a signal to a “harvest protein”. But sometimes, cells manage to resist and regenerate, essentially becoming “zombie cells”. It’s a biological plot that veers into sci-fi horror territory.
When cells are about to die, they send signals that trigger proteins that are supposed to destroy them, but it doesn’t always happen that way: some activate the signal but then resist the “executor proteins”, even in extremely adverse conditions, such as intense radiation.
Enzymes known as caspases are the “harvest proteins” in charge of picking up the cells in your last breath.
Frequently called executorsthese proteases — enzymes that disaggregate peptide bonds through hydrolysis — are catalysts that initiate the process of apoptosisor programmed cell death.
This is how dismember the proteins of a dying cell. These proteins are then reused to support the functions of living cells, explains .
Caspases, which are activated through specific cell death pathwaysthey take away cells that are too compromised — whether by pathogens or molecular damage.
Which almost pushes caspases to the horror sci-fi territory is the fact that they can effectively cause cells on the verge of death to turn into zombies.
A declining cell initially signals an initiator caspase so that it can trigger its own self-destruction, and the initiator induces “effector caspases” to tear your proteins apart.
But this doesn’t always happen so directly. Something that has puzzled scientists for the last fifty years is why caspases cause some cells to teeter on the brink of apoptosis. regenerate tissue damaged and even increase resilience.
These cells start to go into self-destruct modebut in an unlikely twist end up being undead.
In their laboratory at the Weizmann Institute of Science, in Israel, the team of molecular geneticists Eli Arama and Tslil Brown finally discovered how cells programmed to die manage to survive.
The team had previously experimented bomb larvae of fruit flies with ionizing radiation, which should have been lethal at the cellular level.
With improved technologies that would give them a deeper understanding, they recently repeated this experiment using a sensor that identified zombie cells. That’s how they discovered Why do cells at the epithelial, or outer, level of tissue they didn’t all die.
Between aces seven caspases encoded by the genome of the fruit fly (Drosophila melanogaster) are found initiator Dronc and effectors Drice and Dcp-1which are activated by the Dark protein to dismantle cells after the Dronc caspase has been signaled.
Living cells inhibit caspases, but when they are ready to die, this is reversed by a protein familyaptly named Reaperwhich binds to the inhibitor and initiates apoptosis.
There were cells that not only escaped the effects of irradiation but also repaired damaged tissue and multiplied enough to replace almost half of the tissue which could not be recovered. This is the phenomenon of “compensatory proliferation“.
The cells behind this resurrection worthy of Frankenstein they were DARE cells (epithelial cells resistant to radiation-induced apoptosis and activating Dronc) and NARE (epithelial cells resistant to radiation-induced apoptosis and not activating Dronc).
“We identified two populations of epithelial cells resistant to apoptosis that mediate regeneration after ionizing radiation, Dronc-activating (DARE) and non-activating (NARE) cells”, explain the authors of the , recently published in the journal Nature Communications.
“Dronc activity in DARE cells, independent of Dark and effector caspases, drives regeneration both autonomously and non-autonomously in relation to the cell”, they add.
Although the signal for the initiator caspase was activated in these cells, not even a bombardment of radiation could destroy them. Arama thinks this was possible due to a protein that prevented caspase initiator of activating the executors by attaching it to the cell membrane; DARE cells died and tissue was unable to regenerate as easily when this protein was deactivated.
As cells give and slogan they need each other to function efficiently. DARE cells secrete growth signals that give NARE cells an advantage, while NARE cells contribute to homeostasis by preventing DARE cells from multiplying out of control.
DARE cells also prevent the overproliferation of NARE cells. Preventing cell death may actually be harmful in cancerous tumors, giving them the power to resist radiation treatment.
Unraveling how DARE and NARE cells work is an advance that could be used to develop resistant cancer treatments, that would otherwise continue to spread.
