All-Trans Retinoic Acid and Glycated Albumin Reciprocally Influence their Effects in Human Mesangial Cells

2005 ◽  
Vol 75 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Matilde Alique ◽  
Victoria Moreno-Manzano ◽  
Juan Carlos Sepúlveda-Muñoz ◽  
Patricia Reyes-Martín ◽  
Trinidad Parra-Cid ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Mesangial Cells ◽  
Retinoic Acid Receptor ◽  
Glycated Albumin ◽  
Antioxidant Defenses ◽  
Additional Increase ◽  
Human Mesangial Cells ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Cox 2

All-trans-retinoic acid (tRA) modulates in human mesangial cells (MC) antioxidant defenses, the expression of interleukin-1β-induced vascular cell-adhesion molecule-1 (VCAM-1), cyclooxygenase-2 (COX-2), and the retinoic acid-receptor-β (RAR-β). The correlation of the serum levels of glycated hemoglobin A1c with tRA in type 2 diabetes mellitus patients led us to hypothesize that tRA and glycated albumin (GA), the main circulating glycated protein, might mutually interact in MC. We studied 1) the influence of tRA on GA effects in cultured MC: an assessment was made on how pre-incubation with tRA modified the effects of GA on intracellular oxidation and on the expression of mRNA and protein of COX-2 and VCAM-1; and 2) the influence of GA on tRA effects in MC: we studied how the induction of RARβ expression by tRA was modified by GA. Results: GA dose-dependently increased intracellular oxidation and the expression of the molecules involved in leukocyte infiltration, namely COX-2 and VCAM-1. Pre-incubation with tRA exacerbated GA effects by up to a three- to four-fold additional increase. In turn, induction by tRA of RAR-β was fully inhibited by GA. Thus tRA and GA reciprocally influence their effects in MC. It is possible that this interaction may have a pathophysiological or pharmacological role in diabetic nephropathy.

scholarly journals PLZF-RARα, NPM1-RARα, and Other Acute Promyelocytic Leukemia Variants: The PETHEMA Registry Experience and Systematic Literature Review

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1313 ◽  
Author(s):  
Marta Sobas ◽  
Maria Carme Talarn-Forcadell ◽  
David Martínez-Cuadrón ◽  
Lourdes Escoda ◽  
María J. García-Pérez ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Complete Remission ◽  
Acute Promyelocytic Leukemia ◽  
Fusion Gene ◽  
Retinoic Acid Receptor ◽  
Promyelocytic Leukemia ◽  
High Relapse Rate ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Shed Light

It has been suggested that 1–2% of acute promyelocytic leukemia (APL) patients present variant rearrangements of retinoic acid receptor alpha (RARα) fusion gene, with the promyelocytic leukaemia zinc finger (PLZF)/RARα being the most frequent. Resistance to all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested in PLZF/RARα and other variant APLs. Herein, we analyze the incidence, characteristics, and outcomes of variant APLs reported to the multinational PETHEMA (Programa para el Tratamiento de Hemopatias Malignas) registry, and we perform a systematic review in order to shed light on strategies to improve management of these extremely rare diseases. Of 2895 patients with genetically confirmed APL in the PETHEMA registry, 11 had variant APL (0.4%) (9 PLZF-RARα and 2 NPM1-RARα), 9 were men, with median age of 44.6 years (3 months to 76 years), median leucocytes (WBC) 16.8 × 109/L, and frequent coagulopathy. Eight patients were treated with ATRA plus chemotherapy-based regimens, and 3 with chemotherapy-based. As compared to previous reports, complete remission and survival was slightly better in our cohort, with 73% complete remission (CR) and 73% survival despite a high relapse rate (43%). After analyzing our series and performing a comprehensive and critical review of the literature, strong recommendations on appropriate management of variant APL are not possible due to the low number and heterogeneity of patients reported so far.

Expression of human all-trans-retinoic acid receptor β and its ligand-binding domain in Escherichia coli

1995 ◽  
Vol 308 (1) ◽  
pp. 353-359 ◽  
Author(s):  
M Berggren Söderlund ◽  
G Johannesson ◽  
G Fex
Keyword(s):  
Escherichia Coli ◽  
Retinoic Acid ◽  
Ligand Binding ◽  
Retinoic Acid Receptor ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Acid Receptor ◽  
Recombinant Receptors ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

all-trans-Retinoic acid, one of the hormonally active derivatives of vitamin A, occurs physiologically in plasma at a concentration below 10 nmol/l. The methods currently used for its quantification are based on HPLC, need about 1 ml of serum, are relatively laborious and thus not well suited for mass analysis. The affinity and specificity of retinoic acid receptors for all-trans-retinoic acid encouraged us to express both the entire human retinoic acid receptor beta (RAR-beta) and two versions of its retinoic acid-binding domain in Escherichia coli in the hope that these recombinant proteins might be used as binders in a ligand-binding assay for all-trans-retinoic acid. The recombinant receptors, the whole receptor [RAR-beta-(V7-Q448)], corresponding to domains A-F, and the ligand-binding domain [RAR-beta-(E149-Q448)], corresponding to domains D-F, were expressed in the vector pET 3d/BL21 (DE3) as inclusion bodies, solubilized with guanidinium chloride, renatured and purified by ion-exchange chromatography. RAR-beta-(P193-Q448), corresponding to domains E-F, was expressed in the vector pET 3d/BL21(DE3)pLysS, and purified by reversed-phase chromatography. Under non-denaturing conditions, the expressed whole receptor [RAR-beta-(V7-Q448)] and the D-F construct (RAR-beta-(E149-Q448)] behaved chromatographically as monomeric proteins whereas the E-F construct [RAR-beta-(P193-Q448)] had a strong tendency to aggregate. RAR-beta-(V7-Q448) and RAR-beta-(E149-Q448) had similar Kd values for all-trans-retinoic acid (1.4 and 0.6 nmol/l respectively) whereas RAR-beta-(P193-Q448) bound all-trans-retinoic acid less avidly (Kd 9.6 nmol/l). 9-cis-Retinoic acid bound to RAR-beta-(E149-Q448) and RAR-beta-(V7-Q448) as avidly as all-trans-retinoic acid. Competition experiments showed weak or no binding of 4-oxo-all-trans-retinoic acid, 4-oxo-13-cis-retinoic acid, 13-cis-retinoic acid, acitretin and retinol by RAR-beta-(E149-Q448).

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