Regulation of Neuronal Ferritin Heavy Chain, A New Player in Opiate-Induced Chemokine Dysfunction

Abstract

The heavy chain subunit of ferritin (FHC), a ubiquitous protein best known for its iron-sequestering activity as part of the ferritin complex, has recently been described as a novel inhibitor of signaling through the chemokine receptor CXCR4. Levels of FHC as well as its effects on CXCR4 activation increase in cortical neurons exposed to mu-opioid receptor agonists such as morphine, an effect likely specific to neurons. Major actions of CXCR4 signaling in the mature brain include a promotion of neurogenesis, activation of pro-survival signals, and modulation of excitotoxic pathways; thus FHC up-regulation may contribute to the neuronal dysfunction often associated with opiate drug abuse. This review summarizes our knowledge of neuronal CXCR4 function, its regulation by opiates and the role of FHC in this process, and known mechanisms controlling FHC production. We speculate on the mechanism involved in FHC regulation by opiates, and offer FHC as a new target in opioid-induced neuropathology.

Neuronal ferritin heavy chain and drug abuse affect HIV-associated cognitive dysfunction

“…Our previous studies demonstrated the regulation of FHC by morphine and the specific involvement of MORs in this effect (27,57); in vivo or in vitro deletion of FHC in neurons abolished the inhibitory action of morphine exposure on CXCL12/CXCR4 signaling, emphasizing the importance of the FHC/CXCR4 interaction promoted by morphine. Here, we extend these findings to show a similar effect caused by HIV infection in the absence of opiate exposure.…”

Survivin inhibition by an interacting recombinant peptide, derived from the human ferritin heavy chain, impedes tumor cell growth

“…Recently, additional functions have been explored for FTH1, and connections to major signaling pathways have been established. It acts as an inhibitor of signaling exerted by the chemokine receptor CXCR4 in cortical neurons (Abt and Meucci 2011). Ferritin, the spherical molecule of 24 subunits of FTH1 and FTL (ferritin light chain), not only stores iron within cells, but has also been found in the circulation and binds to different cell types.…”

Drugs of Abuse Effects on Immunity and Microbial Pathogenesis

“…There are seven reviews, five original contributions and one brief report. In the reviews by Roy et al, Abt and Meucci and Wang et al, the current status of the consequence of opiates on immune function and opportunistic infection are highlighted (Abt and Meucci 2011;Roy et al 2011;. Although opioid-induced immunosuppression has been demonstrated in cell culture experiments and in animal models, there is a paucity of confirmatory studies in humans.…”