Transcriptional Regulation of Inflammation

Nuclear factor-KB (NF-kB) is a major transcription factor involved in the regulation of inflammation induced by focal cerebral ischemia (1). NF-kB is normally located in the cytoplasm and combines with its natural inhibitor, known as the IkB family. The IkB family consists of iKB-a, IkB-P, and iKB-y. Phosphorylation of IKB-a by an upstream IkB kinase (IKK) liberates NF-kB and allows it to translocate to the nucleus. ROS, cytokines, and excess intracellular Ca2+ might activate IKK during stroke. In the nucleus, NFk-B binds to kB sites, which are specific domains within the promoters of downstream genes to activate their transcription. It is known that a variety of genes involved in inflammation contain functional kB sites within their promoters and are induced by NF-kB; for example, genes that express proteins of TNF-a, ICAM-1, COX-2, and IL-6 are activated by focal ischemia. However, the function of NF-kB in stroke is still controversial. Consistent with a damaging role, mild hypothermia, a robust neuroprotectant, was found to attenuate NFk-B by inhibiting IKK-P and IKK-y following transient focal cerebral ischemia (138). Furthermore, mice deficient in NFk-B's p50 subunit were protected from experimental stroke (139). However, another study reported that rats given an NFk-B inhibitor, diethyldithiocarbamate, experienced enhanced neuron DNA fragmentation and larger infarct volume, compared with controls (140).

Metabolism Masterclass

Metabolism Masterclass

Are You Sick And Tired Of All The Fat-Burning Tricks And Trends That Just Don’t Deliver? Well, Get Set To Discover The Easy, Safe, Fast, And Permanent Way To Mega-Charge Your Metabolism And Lose Excess Fat Once And For All! This Weight Blasting Method Is Easy AND Natural… And Will Give You The Hot Body And Killer Energy Levels You’ve Been Dreaming Of.

Get My Free Ebook

Post a comment