Eukaryotic and prokaryotic phytochelatin synthases differ less in functional terms than previously thought: a comparative analysis of Marchantia polymorpha and Geitlerinema sp. PCC 7407

This paper reports functional studies on the enzyme phytochelatin synthase in the liverwortMarchantia polymorphaand the cyanobacteriumGeitlerinemasp. strain PCC 7407. In vitro activity assays in control samples (cadmium-untreated) showed that phytochelatin synthase was constitutively expressed in both organisms. In the presence of 100 mu M cadmium, in both the liverwort and the cyanobacterium, the enzyme was promptly activated in vitro, and produced phytochelatins up to the oligomer PC4. Likewise,in vivoexposure to 10-36 mu M cadmium for 6-120 h induced in both organisms phytochelatin synthesis up to PC4. Furthermore, the glutathione (GSH) levels inM. polymorphawere constitutively low (compared with the average content in higher plants), but increased considerably under cadmium stress. Conversely, the GSH levels inGeitlerinemasp. PCC 7407 were constitutively high, but were halved under metal treatments. At odds with former papers, our results demonstrate that, as inM. polymorphaand other plants, the cyanobacterial phytochelatin synthase exposed to cadmium possesses manifest transpeptidasic activity, being able to synthesize phytochelatins with a degree of oligomerization higher than PC2. Therefore, prokaryotic and eukaryotic phytochelatin synthases differ less in functional terms than previously thought

Delivery of thyronamines (TAMs) to the brain: A preliminary study

Recent reports highlighted the significant neuroprotective effects of thyronamines (TAMs), a class of endogenous thyroid hormone derivatives. In particular, 3-iodothyronamine (T1AM) has been shown to play a pleiotropic role in neurodegeneration by modulating energy metabolism and neurological functions in mice. However, the pharmacological response to T1AM might be influenced by tissue metabolism, which is known to convert T1AM into its catabolite 3-iodothyroacetic acid (TA1). Currently, several research groups are investigating the pharmacological effects of T1AM systemic administration in the search of novel therapeutic approaches for the treatment of interlinked pathologies, such as metabolic and neurodegenerative diseases (NDDs). A critical aspect in the development of new drugs for NDDs is to know their distribution in the brain, which is fundamentally related to their ability to cross the blood–brain barrier (BBB). To this end, in the present study we used the immortalized mouse brain endothelial cell line bEnd.3 to develop an in vitro model of BBB and evaluate T1AM and TA1 permeability. Both drugs, administered at 1 µM dose, were assayed by high-performance liquid chromatography coupled to mass spectrometry. Our results indicate that T1AM is able to efficiently cross the BBB, whereas TA1 is almost completely devoid of this property

Eukaryotic and prokaryotic phytochelatin synthases differ less in functional terms than previously thought: a comparative analysis of Marchantia polymorpha and Geitlerinema sp. PCC 7407

This paper reports functional studies on the enzyme phytochelatin synthase in the liverwort Marchantia polymorpha and the cyanobacterium Geitlerinema sp. strain PCC 7407. In vitro activity assays in control samples (cadmium-untreated) showed that phytochelatin synthase was constitutively expressed in both organisms. In the presence of 100 µM cadmium, in both the liverwort and the cyanobacterium, the enzyme was promptly activated in vitro, and produced phytochelatins up to the oligomer PC4. Likewise, in vivo exposure to 10–36 µM cadmium for 6-120 h induced in both organisms phytochelatin synthesis up to PC4. Furthermore, the glutathione (GSH) levels in M. polymorpha were constitutively low (compared with the average content in higher plants), but increased considerably under cadmium stress. Conversely, the GSH levels in Geitlerinema sp. PCC 7407 were constitutively high, but were halved under metal treatments. At odds with former papers, our results demonstrate that, as in M. polymorpha and other plants, the cyanobacterial phytochelatin synthase exposed to cadmium possesses manifest transpeptidasic activity, being able to synthesize phytochelatins with a degree of oligomerization higher than PC2. Therefore, prokaryotic and eukaryotic phytochelatin synthases differ less in functional terms than previously though

The 3-iodothyroacetic acid does not cause change in proteins affected by T1AM.

The 3-iodothyroacetic acid (TA1) derives from the metabolism of 3-iodothyronamine and it is highly produced in cell culture medium supplemented with fetal bovine serum. Previous results indicated that, in models of brain cell lines, exogenous T1AM can increase the phosphorylation of proteins involved in signaling cascade, but this could be a pharmacological effect of TA1. Therefore, we evaluate whether TA1 can reproduce T1AM’s effects in the same experimental conditions. Methods: A hybrid line of cancer cells of mouse neuroblastoma and rat glioma (NG108-15) and a human glioblastoma cell line (U-87 MG) were used. Cell lines were treated with TA1 for 24h, ranging from 0.1 to 10 μM. Uptake, cell viability, and protein expression were assessed. Results: TA1 was taken up by cells, even though its concentration in media was almost unchanged upon 24h of incubation. Cell viability was significantly increased by TA1 10 µM in U87-MG cell line. Western blot analysis indicated that TA1 did not altered the expression (Sirtuin 1, p=NS) or the post-translational modifications (pERK/ERK, pCREB/CREB, p=NS) of proteins involved in signaling cascade that are usually affected by pharmacological doses of T1AM. In conclusion, our observations suggest that TA1, differently from T1AM, does not affect phosphorylation of proteins

Efficacy and safety of sunitinib therapy in FDG-PET-positive, iodine-refractory advanced thyroid cancer

no abstract availabl