Disease relevance of Gadd45a

• Injury to the central axons of dorsal root ganglion neurons produces only a minimal induction of Gadd45a while peripheral inflammation is without effect [1].
• DNA damage and DNA damage-inducible protein Gadd45 following ischemia in the P7 neonatal rat [2].
• Furthermore, repairing processes seem to be more active in the penumbra and therefore Gadd45 could have also a protective role in cerebral ischemia [2].
• Increases in DNA lesions and the DNA damage indicator Gadd45 following transient cerebral ischemia [3].

High impact information on Gadd45a

• Western blot analysis demonstrated upregulation of Gadd45a and IAP-1 proteins [4].
• Colocalization with activating transcription factor 3-LI and c-jun mRNA implies that all peripherally injured primary sensory and motor neurons express Gadd45a mRNA [1].
• The growth arrest and DNA damage-inducible gene 45 alpha (Gadd45a) was one of 240 genes found previously by high density oligonucleotide microarray analysis to be regulated in the rat L4 and L5 dorsal root ganglia 3 days after transection of the sciatic nerve (>four-fold up-regulation) [1].
• When axons are allowed to regrow following sciatic nerve crush injury, Gadd45a expression is terminated at later time points, when levels of other markers of injury return towards normal [1].
• Selective up-regulation of the growth arrest DNA damage-inducible gene Gadd45 alpha in sensory and motor neurons after peripheral nerve injury [1].

Biological context of Gadd45a

• The growth arrest and DNA damage response gene Gadd45a appeared to be a direct target of FOXO3a that mediates part of FOXO3a's effects on DNA repair [5].
• The rat Gadd45 cDNA sequence was highly homologous to the previously published human and hamster cDNAs, and was partially similar to the 28S rRNA gene [6].
• DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein [5].
• However, 0.4 microg/kg bw TCDD also altered the expression of Gadd45a and Cyclin D1, suggesting that even low-dose TCDD exposure can alter the expression of genes indicative of cellular stress or DNA damage and associated with cell cycle control [7].
• CONCLUSIONS: Although X-irradiation, etoposide and adriamycinare known spermatogenic mutagens and activators of apoptosis, only X-rays induce slightly Gadd45 expression in testis [8].

Anatomical context of Gadd45a

• This finding indicates that Gadd45 is an inducible gene following the ionizing radiation, not only in cultured cells in vitro, but also in animal tissues in vivo [6].
• The Gadd45a mRNA expression profile investigated by northern blot, RNase protection assay and in situ hybridization in the rat shows negligible constitutive mRNA levels in embryonic, neonatal or adult intact dorsal root ganglia [1].
• Troglitazone induces apoptosis via the p53 and Gadd45 pathway in vascular smooth muscle cells [9].
• This lesioning of DNA is followed by the appearance of the damage-response indicator Gadd45 in the ischemic hemisphere following middle cerebral artery occlusion [3].

Associations of Gadd45a with chemical compounds

• In contrast, along with the induction of vascular smooth muscle cell apoptosis, both the mRNA and protein expression levels of p53 and Gadd45 markedly increased in response to troglitazone [9].
• RESULTS: In whole testis extracts, increases in Gadd45, p21 and cyclin-G expression were detectable after irradiation, but not after etoposide or adriamycin treatments [8].

Regulatory relationships of Gadd45a

• Bax has been shown to promote neuronal death by interacting with Bcl-2 family members while Gadd-45 expression has been associated with suppression of the cell-cycle and DNA repair [10].

Other interactions of Gadd45a

• In addition, these genes especially Hsp70 and Gadd45a might represent promising new candidates indicating WI/R liver damage [11].
• Protein expression was examined on Western blots and by immunohistochemistry for four differentially expressed target genes (Hsp70, Hsp27, Gadd45a and IL-1rI) [11].
• Taken together however, these results suggest that p53, Bax and Gadd-45 may play important roles in the response (damage/recovery) of the brain following excitotoxic injury [10].

Analytical, diagnostic and therapeutic context of Gadd45a

• In neurons, in the infarct core with frank DNA fragmentation shown by in situ TdT-mediated dUTP-biotin nick end labeling (TUNEL) at 24 h, the Gadd45 immunostaining was not visible [3].

References