Delving into the Latest Updates on Elocalcitol with Synapse

PURPOSESkeletal muscle (Skm) plays a key role in regulating energetic metabolism through glucose homeostasis. Several hormones such as Testosterone (T) and Vitamin D (VD) have been shown to affect energy-dependent cell trafficking by determining Insulin (I)-like effects.AIMTo elucidate possible hormone-related differences on muscular metabolic control, we analyzed and compared the effects of T and elocalcitol (elo), a VD analogue, on the activation of energy-dependent cell trafficking, metabolism-related-signal transduction pathways and transcription of gene downstream targets.METHODSHuman fetal skeletal muscle cells (Hfsmc) treated with T or elo were analyzed for GLUT4 localization, phosphorylation/activation status of AKT, ERK1/2, IRS-1 signaling and c-MYC protein expression.RESULTST, similar to elo, induced GLUT4 protein translocation likely in lipid raft microdomains. While both T and elo induced a rapid IRS-1 phosphorylation, the following dynamic in phosphorylation/activation of AKT and ERK1/2 signaling was different. Moreover, T but not elo increased c-MYC protein expression.CONCLUSIONSAll together, our evidence indicates that whether both T and elo are able to affect upstream I-like pathway, they differently determine downstream effects in I-dependent cascade, suggesting diverse physiological roles in mediating I-like response in human skeletal muscle.

01 May 2017·Experimental and Therapeutic MedicineQ4 · MEDICINE

1,25-(OH)2D3 and its analogue BXL-628 inhibit high glucose-induced activation of RhoA/ROCK pathway in HK-2 cells

Q4 · MEDICINE

Article

Author: Liu, Jishi ; Zhang, Wei ; Zhang, Hao ; Huang, Jing ; Yi, Bin ; Yang, Shikun ; Zhang, Ke ; Li, Aimei

It has previously been reported that 1,25-(OH)₂D₃ inhibits high glucose-induced epithelial-to-mesenchymal transition (EMT) in HK-2 cells. However, the mechanism of this renoprotective action remains unclear. Elocalcitol (BXL-628), a vitamin D analog, has been suggested to be effective on the RhoA/Rho associated protein kinase (ROCK) pathway, which serves a crucial role in high glucose-induced EMT. The aim of the present study was to investigate the effect of 1,25-(OH)₂D₃ and its analogue BXL-628 on high glucose-induced activation of the RhoA/ROCK pathway in human renal proximal tubular cells. HK-2 cells were co-treated with high glucose and either 1,25-(OH)2D3 or BXL-628. The RhoA expression levels and ROCK activity of the membrane were assessed via western blot analysis or immunofluorescence. α-smooth muscle actin (α-SMA) and epithelial (E)-cadherin were detected using western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), whereas collagen I and fibronectin levels were measured by ELISA and RT-qPCR. The results demonstrated that 1,25-(OH)₂D₃ and BXL-628 both significantly downregulated the expression of active RhoA and ROCK activity induced by high glucose (P<0.05). Furthermore, the expressions of α-SMA, collagen I, and fibronectin were significantly downregulated at both protein and mRNA (P<0.05) levels, whereas the expression of E-cadherin was significantly increased (P<0.05) by 1,25-(OH)₂D₃ or BXL-628 treatment. In conclusion, the vitamin D receptor agonist 1,25-(OH)₂D₃ and its analogue BXL-628 were both able to attenuate high glucose-induced EMT and extracellular matrix accumulation of HK-2 cells by suppressing the RhoA/ROCK signaling pathway in vitro.

01 Mar 2017·The Journal of Steroid Biochemistry and Molecular BiologyQ2 · BIOLOGY

Potential role for the VDR agonist elocalcitol in metabolic control: Evidences in human skeletal muscle cells

Q2 · BIOLOGY

Article

Author: Di Luigi, Luigi ; Riccieri, Valeria ; Valesini, Guido ; Minisola, Salvatore ; Crescioli, Clara ; Migliaccio, Silvia ; Pisano, Annalinda ; Giordano, Carla ; Cerbelli, Bruna ; Lenzi, Andrea ; Antinozzi, Cristina ; Corinaldesi, Clarissa ; Vannelli, Gabriella Barbara ; Stefanantoni, Katia

Vitamin D plays a pivotal role to maintain skeletal muscle integrity and health. Vitamin D deficiency characterizes inflammatory myopathy (IM) and diabetes, often overlapping diseases involving skeletal muscle damage. Vitamin D receptor (VDR) agonists likely exert beneficial effects in both IM and metabolic disturbances. We aim to evaluate in vitro the effect of elocalcitol, a non-hypercalcemic VDR agonist, on the biomolecular metabolic machinery of human skeletal muscle cells (Hfsmc), vs. insulin (I). We analyzed GLUT4, Flotillin-1, Caveolin-3 and Caveolin-1 cell expression/localization; mTOR, AKT, ERK and 4E-BP1 phosphorylation; IL-6 myokine release; VDR expression. We investigated in vivo vitamin D status in IM subjects, evaluating VDR muscular expression and serum vitamin D with metabolism-related parameters, as glycemia, triglycerides, cholesterol, resistin and adiponectin. In Hfsmc, elocalcitol exerted an I-like effect, promoting GLUT4 re-localization in Flotillin-1, Caveolin-3 and Caveolin-1 positive sites and mTOR, AKT, ERK, 4E-BP1 activation; it enhanced IL-6 myokine release. IM subjects, all normoglycemic, showed VDR/vitamin D deficiency that, together with high lipidemic and resistin profile, possibly increases the risk to develop metabolic diseases. VDR agonists as elocalcitol may be therapeutic tools for skeletal muscle integrity/function maintenance, an indispensable condition for health homeostasis.

100 Deals associated with Elocalcitol

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KEGG	Wiki	ATC	Drug Bank
-	-	-	DB06194

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Infertility, Male	Phase 1	-	F. Hoffmann-La Roche Ltd.	-
Osteoporosis, Postmenopausal	Phase 1	US	-	-
Prostatic Hyperplasia	Phase 1	-	F. Hoffmann-La Roche Ltd.	-
Urinary Bladder, Overactive	Phase 1	-	F. Hoffmann-La Roche Ltd.	-
Osteogenesis Imperfecta	Preclinical	US	Adge Pharmaceuticals Inc.	-
Rett Syndrome	Preclinical	US	Adge Pharmaceuticals Inc.	-
Infertility, Male	Discovery	-	F. Hoffmann-La Roche Ltd.	-
Prostatic Hyperplasia	Discovery	-	F. Hoffmann-La Roche Ltd.	-
Prostatitis	Discovery	-	F. Hoffmann-La Roche Ltd.	-
Urinary Bladder, Overactive	Discovery	-	F. Hoffmann-La Roche Ltd.	-