Related Experiment Video

Updated: May 26, 2026

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

Release of mitochondrial apoptogenic factors and cell death are mediated by CK2 and NADPH oxidase

Gab Seok Kim1, Joo Eun Jung, Purnima Narasimhan

  • 1Department of Neurosurgery, Stanford University School of Medicine, Stanford, California 94305-5487, USA.

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
|December 8, 2011
PubMed

Insights

Casein kinase 2 (CK2) inhibition exacerbates neuronal death after ischemic brain injury by promoting oxidative stress and DNA damage. This mechanism involves NOX2 activation, reactive oxygen species release, and apoptotic factor release from mitochondria.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Neuronal death following cerebral ischemia and reperfusion is linked to NADPH oxidase subunit NOX2 activation and oxidative stress.
  • Casein kinase 2 (CK2) inhibition promotes neuronal survival, but the underlying mechanism remains unclear.

Purpose of the Study:

  • To elucidate the mechanism by which CK2 inhibition influences neuronal survival or death after ischemic brain injury.
  • To investigate the role of NOX2, oxidative stress, and apoptotic pathways in CK2-mediated effects.

Main Methods:

  • Utilized copper/zinc-superoxide dismutase transgenic (SOD1 Tg) and gp91 knockout (KO) mice subjected to middle cerebral artery occlusion (MCAO).
  • Administered CK2 inhibitors (pharmacological and ischemic reperfusion) and tetrabromocinnamic acid (TBCA).
  • Assessed CK2 subunit degradation, dephosphorylation, poly(ADP-ribose) polymer accumulation, apoptosis-inducing factor (AIF) and cytochrome c release, DNA damage markers (8-hydroxy-2'-deoxyguanosine, H2A.X phosphorylation), and brain infarction.

Main Results:

  • CK2 inhibition, particularly under ischemic conditions, enhanced poly(ADP-ribose) polymer accumulation, AIF translocation, and cytochrome c release.
  • Enhanced CK2 inhibition increased markers of DNA damage, including 8-hydroxy-2'-deoxyguanosine and phosphorylated H2A.X.
  • In SOD1 Tg and gp91 KO mice, CK2 inhibition with TBCA resulted in reduced AIF and cytochrome c release compared to WT mice.
  • CK2 inhibition in gp91 KO mice did not exacerbate brain infarction following ischemia-reperfusion.

Conclusions:

  • NOX2 activation, induced by CK2 inhibition, releases reactive oxygen species that trigger mitochondrial release of apoptogenic factors and DNA damage, contributing to neuronal death in ischemic brain injury.
  • The findings suggest a critical role for the NOX2-CK2 interaction in regulating cell death pathways after cerebral ischemia.

More Related Videos

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation06:12

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation

Published on: May 3, 2024

Strategies for Tracking Anastasis, A Cell Survival Phenomenon that Reverses Apoptosis12:55

Strategies for Tracking Anastasis, A Cell Survival Phenomenon that Reverses Apoptosis

Published on: February 16, 2015

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...