Kinetics of GADD45α, TP53 and CASP3 gene expression in the rat lens in vivo in response to exposure to double threshold dose of UV-B radiation

• Published in: Experimental eye research 2012-04, Vol.97 (1), p.19-23
• Main Authors: Galichanin, Konstantin, Svedlund, Jessica, Söderberg, Per
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; CASP3; Caspase 3 - genetics; Cataract - etiology; Cataract - genetics; Cataracts; Cell Cycle Proteins - genetics; Evolution; Evolutionary genetics; Eye; Eye lens; Female; Gadd45A protein; GADD45α; Gene expression; Gene Expression Regulation - physiology; Genomes; Kinetics; lens; Lens, Crystalline - metabolism; Lens, Crystalline - radiation effects; Medicin och hälsovetenskap; Nuclear Proteins - genetics; p53 protein; Polymerase chain reaction; Radiation; Radiation Injuries, Experimental - etiology; Radiation Injuries, Experimental - genetics; Radiation Tolerance; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; RNA, Messenger - metabolism; Stress; stress sensing; Time Factors; TP53; Tumor Suppressor Protein p53 - genetics; Ultraviolet Rays - adverse effects; UVR
• ISSN: 0014-4835; 1096-0007; 1096-0007
• DOI: 10.1016/j.exer.2012.02.003

The purpose of the present study was to investigate the evolution of expression of mRNA message for the genes for the genome stress sensor GADD45α, the apoptosis initiator TP53 and the apoptosis executor CASP3 in the rat lens in vivo in response to exposure to UVR around 300 nm. Forty six week old female albino Sprague-Dawley rats were unilaterally exposed to double threshold dose for cataract induction, 8 kJ/m2 (8.9 W/m2 for 15 min), of UVR (λmax = 300 nm). The animals were sacrificed at 1, 5, 24 and 120 h following exposure to UVR-B. For each of the GADD45α, TP53 and CASP3 genes, respectively, mRNA expression in the lenses was measured by quantitative RT-PCR. It was found that expression of mRNA for GADD45α transiently increases between 5 and 24 h after exposure. TP53 is slightly downregulated in exposed lenses at 1 and 5 h after exposure and thereafter the mRNA expression increases with a constant rate of 9.4∗10−3 rel. units/h to a 1.8 fold increase at 120 h after exposure. Expression of mRNA for CASP3 is downregulated at 1, 5 and 24 h after in vivo exposure and then increases with a constant rate of 4.7∗10−3 rel. units/h, upto a 1.3 fold upregulation at 120 h. Double threshold dose of UVR, for short delay onset of cataract, in vivo causes a transient upregulation of the stress sensor GADD45α, a concurrent downregulation of TP53 and CASP3, followed by a constant upregulation of TP53 that precedes a constant upregulation of CASP3. ► UVR-B exposure induces downregulation of TP53 and CASP3 in early latencies in the rat lens. ► UVR-B exposure induces upregulation of TP53 and CASP3 in later latencies in the rat lens. ► Expression of TP53 precedes expression of CASP3 in the rat lens after in vivo exposure to UVR-B. ► UVR-B exposure induces transient upregulation of GADD45α between 5 h and 24 h.