Effects of Prolyl Hydroxylase Inhibitor L-mimosine on Dental Pulp in the Presence of Advanced Glycation End Products

INTRODUCTION Proangiogenic prolyl hydroxylase (PHD) inhibitors represent a novel approach to stimulate tissue regeneration. Diabetes mellitus involves the accumulation of advanced glycation end products (AGEs). Here we evaluated the impact of AGEs on the response of human pulp tissue to the PHD inhibitor L-mimosine (L-MIM) in monolayer cultures of dental pulp-derived cells (DPCs) and tooth slice organ cultures. METHODS In monolayer cultures, DPCs were incubated with L-MIM and AGEs. Viability was assessed based on formazan formation, live-dead staining, annexin V/propidium iodide, and trypan blue exclusion assay. Vascular endothelial growth factor (VEGF), interleukin (IL)-6, and IL-8 production was evaluated by quantitative polymerase chain reaction and immunoassays. Furthermore, expression levels of odontoblast markers were assessed, and alizarin red staining was performed. Tooth slice organ cultures were performed, and VEGF, IL-6, and IL8 levels in their supernatants were measured by immunoassays. Pulp tissue vitality and morphology were assessed by MTT assay and histology. RESULTS In monolayer cultures of DPCs, L-MIM at nontoxic concentrations increased the production of VEGF and IL-8 in the presence of AGEs. Stimulation with L-MIM decreased alkaline phosphatase levels and matrix mineralization also in the presence of AGEs, whereas no significant changes in dentin matrix protein 1 and dentin sialophosphoprotein expression were observed. In tooth slice organ cultures, L-MIM increased VEGF but not IL-6 and IL-8 production in the presence of AGEs. The pulp tissue was vital, and no signs of apoptosis or necrosis were observed. CONCLUSIONS Overall, in the presence of AGEs, L-MIM increases the proangiogenic capacity, but decreases alkaline phosphatase expression and matrix mineralization.

Vital function for PRELI and essential requirement for its LEA motif

Proteins containing the late embryogenesis abundant (LEA) motif comprise an evolutionarily conserved family, long postulated to protect plant embryos from stress and death. However, the significance of LEA-containing proteins and the mechanisms behind their function remain undetermined. Here we show that PRELI, a mammalian protein that possesses tandem repeats of the LEA motif, can protect cells against staurosporine, TNF-α or UV irradiation-induced apoptosis. We found that key to PRELI-dependent mechanisms that promote cell resistance to death are the stabilization of the respiratory chain, upholding of mitochondrial membrane potential and retention of apoptogenic molecules. By in vitro and in vivo studies, we also show that the expression of mutant PRELI/LEA- proteins lacking the LEA motif, results in the complete loss of PRELI's anti-apoptotic functions. Collectively, our data uncover a new molecular player in the control of apoptosis and support the hypothesis that LEA-containing proteins are evolutionarily conserved cell protectors against stress and death. ^

Letter from Stephen Longfellow to Daniel Appleton White, 1799 May 29

Stephen Longfellow wrote this letter in Portland, Maine on May 29, 1799; it was sent to his friend, Daniel Appleton White, in Medford, Massachusetts. In the letter, Longfellow describes the Election Day festivities among the "plebeans" in Portland, which he apparently found both amusing and upsetting. He compares the horses pulling their sleds to Don Quixote's horse, Rocinante. He also writes about mutual friends, including John Henry Tudor and Jabez Kimball, and bemoans the behavior of the current members of Phi Beta Kappa among the Harvard College undergraduates, whom he insists have sunk the society below its former "exalted station."

The history and religion of the Samaritans /

"Reprinted from Bibliotheca sacra for July, 1906."

Grace book A, containing the proctors' accounts and other records of the University of Cambridge for the years 1454-1488.

The records are in Latin.

Maurit. Herm. Ed. Meieri Opuscula academica.

Bibliographical foot notes.

The American annual cyclopaedia and register of important events of the year ...

Mode of access: Internet.

Epistolario.

Vols. 3-6, <8-9, 11-21> have imprint: Firenze, L.S. Olschki.

Memorial for Archibald Douglas of Douglas, esq; and for Margaret, dutchess of Douglas, and Charles, duke of Queensberry and Dover, his curators, defenders;

Concerning the claim of Archibald Douglas as heir of tailzie to his uncle, Archibald, duke of Douglas.

Discorso pronunziato nel giorno 5 giugno 1881 in occasione della vigesima commemorazione funebre a Camillo Cavour in Santena /

Mode of access: Internet.

Biografìa del conte di Cavour.

Caption title.

Frederic Lord Leighton : late president of the Royal Academy of Arts : an illustrated record of his life and work /

Includes index.

Cavour /

Mode of access: Internet.

The life, letters and work of Frederic Leighton,

Plates, with the exception of the photogravures, mounted.

Gustave III, roi de Suède, et Anckarstroem, 1746-1792.

"Discours et correspondance du roi": p. [285]-416.