Abstract
The present study supports previous finding that vitamin A can induce and accelerate lens regeneration in pigmented epithelial cells (PECs) of dorsal iris not only in amphibians but also in young and adult swiss albino mice, guinea pig, rabbit and pigs. In lens regeneration, several workers have shown that vitamin A possesses the mitogenic activity which causes functional impairment of retinoid receptors and thereby inhibits the lens regeneration. The purpose of present study is to know how retinoids and their derivatives interact with Retinoid X receptor (Rxr alpha) and thus helping in lens regeneration. The docking studies of human and mice Rxr alpha were performed against vitamin A and 9-cis retinoic acid (vitamin A1) using autodock and the results were analyzed using Discovery Studio from Accelrys. The results show that there is a significant similarity in interaction energy of Rxr alpha of mice and human. The highest rank docked energy of Rxr alpha mice with vitamin A was -11.65 kcal, which was much closed to -11.83 kcal of 9-cis retinoic acid. Similarly, in human Rxr alpha receptor, the highest docked energy showed the significant similarity with vitamin A (-12.19 kcal) and 9- cis retinoic acid (-12.14 kcal). This study suggests that vitamin A shows effect on proliferation and differentiation similar to the 9-cis retinoic acid and also proves that vitamin A acts on Retinoid X alpha receptors and enhance lens regeneration in mammals.
Highlights
Lens regeneration provides a clear example of trans-differentiation of one differentiated cellular type having a distinctive pattern of metabolic activities to another cellular type, which is morphologically and biochemically distinct from the original
Its derivatives were found to accelerate lens regeneration in amphibian frogs and in mammals like swiss albino mice, rabbit, guinea pigs and pigs (Shekhawat et al, 2001).It has been reported that vitamin A (Retinol) is the immediate precursor to two important active metabolites: Retinal and Retinoic acid
The docking of Retinoid X receptor alpha of human and mice with vitamin A and 9-cis retinoic acid were performed in silico
Summary
Lens regeneration provides a clear example of trans-differentiation of one differentiated cellular type having a distinctive pattern of metabolic activities to another cellular type, which is morphologically and biochemically distinct from the original. The ability of all-trans retinoic acid to regulate expression of several hundred genes through binding to nuclear transcription factors is believed to mediate most of these functions. It has been reported that at molecular level the retinoic acid receptors are members of super family of intracellular hormone receptor which functions as regulator of gene transcription. These receptors comprise two distinct families, the retinoic acid receptor (RAR) family and the Retinoid X receptor (RXR) family; both families have subfamilies which have alpha, beta and gamma receptor proteins (Ralff and Ribeiro, 1995). Recent methodologies like In silico docking and simulation studies were considered beneficial for this research as it provides the result with more accuracy in relatively very less time
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