Dr. Zhi-Qi Xiong
Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (Cina)
24th April 2014, 12:00-13:00
MBC, Via Nizza 52, Seminars' Room
Hosts: Maurizio Giustetto, Ferdinando Di Cunto
A paper from the group of Emanuela Tolosano described a key role for the heme exporter FLVCR1a in hepatic heme metabolism and cytochrome P450 function.
The liver has one of the highest rate of synthesis of heme, 50% of of which is used to support the synthesis of cytochromes P450. These enzymes metabolize exogenous and endogenous compounds, including natural products, hormones, drugs, and carcinogens. FLVCR1a is a ubiquitously expressed plasma membrane heme exporter that has been shown to control intracellular heme content in hematopoietic lineages. In a recent paper published on Gastroenterology, Vinchi et al. addressed FLVCR1a function in the liver, by generating mice with conditional disruption of Flvcr1a in hepatocytes. With aging, these mice accumulated heme and iron in liver. As a mechanism to compensate for the lack of heme export, heme catabolism (HO-1) and iron storage (Ferritin) are increased. These findings highlight a crucial role for FLVCR1a in the maintenance of hepatic heme homeostasis. Flvcr1a export function was found closely associated with heme biosynthesis, required to sustain cytochrome induction. Hepatic heme accumulation in these mice causes the early inhibition of heme synthesis and increased degradation of heme, which finally reduced the expression and activity of cytochromes P450. As a consequence, these mice show a reduced ability to upregulate cytochrome P450 in response to drugs and xenobiotics. These observations suggest a direct implication of heme export in cytochromes P450 function and drug metabolism.
A paper from the groups of Ferdinando Di Cunto and Paola Defilippi establishes the crucial role of the p140Cap protein in synaptic plasticity and memory.
One of the major challenges in the neuroscience field is to identify the molecular and cellular mechanisms implicated in the establishment and in retrival of memories. Dendritic spines, i.e. small protrusions of neuronal cells which receive most of the excitatory inputs in the brain, are fundamental structures under this perspective. Indeed, the organization of dendritic spines and their efficiency in synaptic transmission are dramatically modified by experience. It has recently been shown that a molecular pathway linking dynamic microtubules to the actin cytoskeleton, involving the p140Cap protein, is crucial for the maintenance of dendritic spines. However it remained to be established whether this pathway is actually important for memory and how it may operate in detail. In a recent paper published on the Journal of Neuroscience, Daniele Repetto, Paola Camera and collaborators have established that p140Cap is important for different types memory. Moreover they have dissected the molecular cascade linking p140Cap to the reorganization of the dendritic spine cytoskeleton. These studies could be of great relevance for a better understanding of many congenital and acquired human diseases affecting memory capabilities, such as intellectual disabilities and neurodegenrative disorders.
Convenzione per l'attivazione di una Cell Factory presso l'Università di Torino (Torino, 28 novembre 2013).
Oggi nel Salone del Rettorato, il Rettore dell'Università degli Studi di Torino, Prof. Gianmaria Ajani, e il Responsabile Emea LA di Fresenius Medical Care, Prof. Emanuele Gatti, hanno firmato la Convenzione per l'attivazione di una Cell Factory presso l'Università di Torino per la produzione di cellule staminali finalizzate alla terapia dell'insufficienza renale ed epatica.