Low concentrations of zinc in gastric mucosa are associated with increased severity of Helicobacter pylori-induced inflammation.

Background: Chronic Helicobacter pylori infection is the most common cause of gastric cancer. H. pylori induces oxidative stress while zinc deficiency results in increased sensitivity to it.

Activation of the calcium/calmodulin-dependent protein kinases as a consequence of oxidative stress.

Oxygen radicals have diverse effects on cells. In many cases, exposure to reactive oxygen intermediates (ROI) can induce cell death. Conversely, there is also evidence that suggests oxygen radicals can activate signaling pathways that are thought to prevent cell death.

Molecular pathways leading to oxidative stress-induced phosphorylation of Akt.

Oxidative stress can activate a variety of intracellular signaling pathways. The authors previously reported the CaM-K inhibitor KN-93 inhibited hydrogen peroxide-induced phosphorylation of Akt on threonine 308 (T308). In this report they demonstrate that phosphorylation of T308 in response to hydrogen peroxide treatment is not inhibited by LY294002, suggesting that phosphorylation of this residue in response to oxidative stress is largely PI3K independent.

Inhibition of the CaM-kinases augments cell death in response to oxygen radicals and oxygen radical inducing cancer therapies in MCF-7 human breast cancer cells.

Many cancer treatments induce cell death through lethal oxidative stress. Oxidative stress also induces the activation of the calcium/calmodulin-dependent kinases (CaM-Ks), CaM-KII and CaM-KIV. In turn, the CaM-Ks are known to induce the activation of antiapoptotic signaling pathways, such as Akt, ERK, and NF-kappaB in many different cell types.

Calcium/calmodulin-dependent protein kinases as potential targets in cancer therapy.

In this review the authors discuss the expression and activation of a family of protein kinases known as the calcium/calmodulin-dependent kinases (CaM-kinase) and the role that these kinases have in the activation of antiapoptotic signalling pathways. In addition, the authors outline a novel mechanism of activation of these kinases by oxidative stress. Founded on this novel mechanism of activation and the role that these kinases have in activating antiapoptotic signalling pathways, the authors propose that the CaM-kinases would make very good targets for sensitising cancer cells to certain therapeutic treatments.

Calcium/calmodulin-dependent kinase I and calcium/calmodulin-dependent kinase kinase participate in the control of cell cycle progression in MCF-7 human breast cancer cells.

Calcium is universally required for cell growth and proliferation. Calmodulin is the main intracellular receptor for calcium. Although calcium and calmodulin are well known to be required for cell cycle regulation, the target pathways for their action remain poorly defined.

Inhibition of CREB transcriptional activity in human T lymphocytes by oxidative stress.

Hydrogen peroxide (HP) induced the phosphorylation of cAMP response element binding protein (CREB) on Ser133 in Jurkat T lymphocytes via p38 and MSK1. Although CREB Ser133 was phosphorylated, increases in HP-stimulated CREB-mediated transcription were absent. T lymphocyte stimulation with anti-CD3 and anti-CD28 induced CREB Ser133 phosphorylation, as well as CREB-mediated transcriptional activity.

Models of anergy in the human Jurkat T cell line.

We investigated two model systems to study anergy in a human T cell line. OKT3 or calcium ionophore stimulation of Jurkat cells, in the absence of costimulation, resulted in a steep reduction in the transcription and secretion of IL-2 in response to subsequent stimulation via CD3 and CD28. Treatment of anergic Jurkat cells with the combination of the phorbol ester, PMA, and ionomycin restored IL-2 production in cells rendered anergic by both mechanisms.

Participation of the calcium/calmodulin-dependent kinases in hydrogen peroxide-induced Ikappa B phosphorylation in human T lymphocytes.

NF-kappaB is an important transcription factor that has a role in a variety of responses such as inflammation, oncogenesis, apoptosis, and viral replication. Oxidative stress is well known to induce the activation of NF-kappaB. Cells can be exposed to either endogenously produced oxidants or oxidants produced by surrounding cells.