Inhibitory effect of all-trans retinoic acid on androgen-induced growth of mouse seminal vesicles in vivo and its mechanism

2005 ◽  
Vol 24 (9) ◽  
pp. 467-474
Author(s):  
Hideki Sato ◽  
Nozomu Tanji ◽  
Motomu Tsuji ◽  
Nobuyuki Terada ◽  
Kenshi Yamasaki ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Reductase Activity ◽  
Inhibitory Effect ◽  
Seminal Vesicles ◽  
Thymidine Uptake ◽  
Binding Assays ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

We examined the effect of all-trans retinoic acid (ATRA) on the androgen-induced growth of mouse seminal vesicles (SVs) in vivo and its mechanisms. Testosterone propionate (TP) alone or with ATRA was injected daily into adult castrated BALB/c mice. Injections of ATRA significantly inhibited the TP-induced growth of SVs in terms of wet weight and DNA synthesis by a pair of SVs evaluated by [3H]thymidine uptake. The bromodeoxyuridine labelling index showed that ATRA inhibited the proliferation of both epithelial and stromal cells. Immunoreactivity for retinoic acid receptor-a was found in the basal epithelial cells. Injections of ATRA affected neither 5a-reductase activity nor the expression of mRNAs for TGF-b1, 2 and 3 and TGF-b receptor 1 and 2 in the SVs. However, androgen receptor (AR) binding assays and Western blotting revealed a decrease in AR without a change in ligand-binding affinity. The present study showed that retinoid inhibited the androgen-induced growth of mouse SVs in vivo, and suggests that a decrease in AR is one of its mechanisms.

scholarly journals The mechanism of all-trans retinoic acid in the regulation of apelin expression in vascular endothelial cells

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Hongyun Shi ◽  
Lanhui Yuan ◽  
Huibin Yang ◽  
Aimin Zang
Keyword(s):  
Endothelial Cells ◽  
Retinoic Acid ◽  
Vascular Endothelial Cells ◽  
Retinoic Acid Receptor ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

The apelin gene can promote vascular endothelial cell (VEC) proliferation, migration, and angiogenesis. However, the molecular mechanism for regulation of the apelin gene is still unknown. Real-time PCR and Western blotting analysis were employed to detect the effect of all-trans retinoic acid (ATRA) in up-regulating apelin expression in human umbilical vein endothelial cells (HUVECs). Furthermore, the in vivo study also indicated that ATRA could increase apelin expression in balloon-injured arteries of rats, which is consistent with the results from the cultured HUVECs. To ensure whether retinoic acid receptor (RAR) α (RARα) could be induced by ATRA in regulating apelin, the expression of RARα was tested with a siRNA method to knock down RARα or adenovirus vector infection to overexpress RARα. The results showed that ATRA could up-regulate apelin expression time- and dose- dependently in HUVECs. ATRA could induce a RARα increase; however, the expression of RARβ and RARγ were unchanged. The blocking of RARα signaling reduced the response of apelin to ATRA when HUVECs were treated with RARα antagonists (Ro 41-5253) or the use of siRNA against RARα (si-RARα) knockdown RARα expression before using ATRA. In addition, induction of RARα overexpression by infection with pAd-GFP-RARα further increased the induction of apelin by ATRA. These results suggested that ATRA up-regulated apelin expression by promoting RARα signaling.

scholarly journals Proteomic Studies of Primary Acute Myeloid Leukemia Cells Derived from Patients Before and during Disease-Stabilizing Treatment Based on All-Trans Retinoic Acid and Valproic Acid

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2143
Author(s):  
Maria Hernandez-Valladares ◽  
Rebecca Wangen ◽  
Elise Aasebø ◽  
Håkon Reikvam ◽  
Frode S. Berven ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Acute Myeloid Leukemia ◽  
Retinoic Acid ◽  
Protein Kinase ◽  
Myeloid Leukemia ◽  
Rna Metabolism ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Acute Myeloid

All-trans retinoic acid (ATRA) and valproic acid (VP) have been tried in the treatment of non-promyelocytic variants of acute myeloid leukemia (AML). Non-randomized studies suggest that the two drugs can stabilize AML and improve normal peripheral blood cell counts. In this context, we used a proteomic/phosphoproteomic strategy to investigate the in vivo effects of ATRA/VP on human AML cells. Before starting the combined treatment, AML responders showed increased levels of several proteins, especially those involved in neutrophil degranulation/differentiation, M phase regulation and the interconversion of nucleotide di- and triphosphates (i.e., DNA synthesis and binding). Several among the differentially regulated phosphorylation sites reflected differences in the regulation of RNA metabolism and apoptotic events at the same time point. These effects were mainly caused by increased cyclin dependent kinase 1 and 2 (CDK1/2), LIM domain kinase 1 and 2 (LIMK1/2), mitogen-activated protein kinase 7 (MAPK7) and protein kinase C delta (PRKCD) activity in responder cells. An extensive effect of in vivo treatment with ATRA/VP was the altered level and phosphorylation of proteins involved in the regulation of transcription/translation/RNA metabolism, especially in non-responders, but the regulation of cell metabolism, immune system and cytoskeletal functions were also affected. Our analysis of serial samples during the first week of treatment suggest that proteomic and phosphoproteomic profiling can be used for the early identification of responders to ATRA/VP-based treatment.

scholarly journals All-Trans Retinoic Acid Increases DRP1 Levels and Promotes Mitochondrial Fission

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1202
Author(s):  
Bojjibabu Chidipi ◽  
Syed Islamuddin Shah ◽  
Michelle Reiser ◽  
Manasa Kanithi ◽  
Amanda Garces ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Mitochondrial Fission ◽  
Normal Function ◽  
Mitochondrial Network ◽  
Protein Levels ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Area And Perimeter

In the heart, mitochondrial homeostasis is critical for sustaining normal function and optimal responses to metabolic and environmental stressors. Mitochondrial fusion and fission are thought to be necessary for maintaining a robust population of mitochondria, and disruptions in mitochondrial fission and/or fusion can lead to cellular dysfunction. The dynamin-related protein (DRP1) is an important mediator of mitochondrial fission. In this study, we investigated the direct effects of the micronutrient retinoid all-trans retinoic acid (ATRA) on the mitochondrial structure in vivo and in vitro using Western blot, confocal, and transmission electron microscopy, as well as mitochondrial network quantification using stochastic modeling. Our results showed that ATRA increases DRP1 protein levels, increases the localization of DRP1 to mitochondria in isolated mitochondrial preparations. Our results also suggested that ATRA remodels the mitochondrial ultrastructure where the mitochondrial area and perimeter were decreased and the circularity was increased. Microscopically, mitochondrial network remodeling is driven by an increased rate of fission over fusion events in ATRA, as suggested by our numerical modeling. In conclusion, ATRA results in a pharmacologically mediated increase in the DRP1 protein. It also results in the modulation of cardiac mitochondria by promoting fission events, altering the mitochondrial network, and modifying the ultrastructure of mitochondria in the heart.

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