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Metallothioneins (MTs) constitute a family of proteins characterized by a high heavy metal [Zn(II), Cu(I)] content and also by an unusual cysteine abundance. Mammalian MTs are comprised of four major isoforms designated MT-1 trough MT-4. MT-1 and MT-2 are expressed in most tissues including the brain, whereas MT-3 (also called growth inhibitory factor) and(More)
The influence of protein kinase A activity on transport of newly synthesized vesicular stomatitis virus G glycoprotein along the exocytic pathway was examined. Transport of vesicular stomatitis virus G glycoprotein to the cell surface was inhibited by N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), a selective inhibitor of protein kinase(More)
Following exercise, AMP-activated protein kinase (AMPK) activity is increased several fold in rat liver and adipose tissue as well as muscle; however, the mechanism by which this occurs is not known. Interleukin-6 (IL-6) is released from muscle in large amounts during and after sustained physical activity resulting in up to 100-fold increases in its plasma(More)
We have evaluated the physiological relevance of metallothionein-1+2 (MT-1+2) in the CNS following damage caused by a focal cryolesion onto the cortex. In comparison to normal mice, transgenic mice overexpressing the MT-1 isoform (TgMTI* mice) showed a significant decrease of the number of activated microglia/macrophage and of CD3+ T lymphocytes in the area(More)
We have examined the role played by protein kinase A (PKA) in vesicle-mediated protein transport from the trans-Golgi network (TGN) to the cell surface. In vivo this transport step was inhibited by inhibitors of PKA catalytic subunits (C-PKA) such as the compound known as H89 and a myristoylated form of the inhibitory peptide sequence contained in the(More)
The aim of the present study was to test the hypothesis that peroxisome proliferator activated receptor-gamma coactivator (PGC) 1alpha is required for exercise-induced adaptive gene responses in skeletal muscle. Whole body PGC-1alpha knockout (KO) and littermate wild-type (WT) mice performed a single treadmill-running exercise bout. Soleus and white(More)
Injury to the central nervous system (CNS) elicits an inflammatory response involving activation of microglia, brain macrophages, and astrocytes, processes likely mediated by the release of proinflammatory cytokines. In order to determine the role of interleukin-6 (IL-6) during the inflammatory response in the brain following disruption of the blood-brain(More)
In this study we have evaluated the primary astroglial reactivity to an injection of N-methyl-D-aspartate into the right sensorimotor cortex, as well as the secondary astroglial response in the thalamic ventrobasal complex, caused by the anterograde degeneration of descending corticothalamic fibres and/or target deprivation of the developing thalamic(More)
To characterize the physiological role of metallothioneins I and II (MT-I+II) in the brain, we have examined the chronological effects of a freeze injury to the cortex in normal and MT-I+II null mice. In normal mice, microglia/macrophage activation and astrocytosis were observed in the areas surrounding the lesion site, peaking at approximately 1 and 3 d(More)
A number of intracellular proteins that are protective after brain injury are classically thought to exert their effect within the expressing cell. The astrocytic metallothioneins (MT) are one example and are thought to act via intracellular free radical scavenging and heavy metal regulation, and in particular zinc. Indeed, we have previously established(More)