Does ER stress cause apoptosis?

If the stress is prolonged, or the adaptive response fails, apoptotic cell death ensues. Many studies have focused on how this failure initiates apoptosis, as ER stress-induced apoptosis is implicated in the pathophysiology of several neurodegenerative and cardiovascular diseases.

What is endoplasmic reticulum stress-induced apoptosis?

ER stress-induced cell death. Under ER stress, PERK is activated and phosphorylates and inactivates eIF2a. This results in the selective induction of ATF4 and its downstream proteins CHOP and Noxa, resulting in cell death. JNK can induce apoptosis by inhibiting anti- apoptotic proteins such as Bcl-2 and Bcl-xL.

What is ER stress in cells?

ER stress occurs when the capacity of the ER to fold proteins becomes saturated. ER stress may be caused by factors that impair protein glycosylation or disulfide bond formation, or by overexpression of or mutations in proteins entering the secretory pathway.

What is ER stress caused by?

ER stress may be caused by factors that impair protein glycosylation or disulfide bond formation, or by overexpression of or mutations in proteins entering the secretory pathway. Ultimately, signaling from these stress-sensing proteins protects the cell or, alternatively, promotes cell death.

What does caspase-3 do in apoptosis?

Caspase-3 is known as an executioner caspase in apoptosis because of its role in coordinating the destruction of cellular structures such as DNA fragmentation or degradation of cytoskeletal proteins (1).

How does Celastrol cause apoptosis in cancer cells?

Celastrol is a natural bioactive compound that was recently shown to increase ROS levels and cause apoptosis in cancer cells. However, the underlying mechanism for this cytotoxic action remains unclear and direct molecular targets of Celastrol have not been identified.

What kind of enzyme does Celastrol bind to?

Results:Our data show that Celastrol directly binds to an antioxidant enzyme, peroxiredoxin-2 (Prdx2), which then inhibits its enzyme activity at both molecular and cellular level.

How is Celastrol used to treat gastric cancer?

Inhibition of Prdx2 by Celastrol increased cellular ROS levels and led to ROS-dependent endoplasmic reticulum stress, mitochondrial dysfunction, and apoptosis in gastric cancer cells. Functional tests demonstrated that Celastrol limits gastric cancer cells, at least in part, through targeting Prdx2.