title: 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.
abstract: 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/m(2) (8.9 W/m(2) for 15 min), of UVR (λ(max) = 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.
authors.affiliation: St. Erik's Eye Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. konstantin.galichanin@neuro.uu.se
authors.forename: Konstantin
authors.initials: K
authors.lastname: Galichanin
authors.forename: Jessica
authors.initials: J
authors.lastname: Svedlund
authors.forename: Per
authors.initials: P
authors.lastname: Söderberg
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000235:genetics*; D002386:Cataract / Q000209:etiology / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D007908:Lens, Crystalline / Q000378:metabolism / Q000528:radiation effects*; D009687:Nuclear Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000235:genetics*; D011836:Radiation Tolerance; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D000097642:GADD45 Proteins
chemical_list: D053148:Caspase 3; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C499073:Gadd45a protein, rat; D000097642:GADD45 Proteins; C505410:Casp3 protein, rat