The regenerative repair response to folic acid and ischemia-reperfusion injury is characterized by different patterns of renal tubular cell proliferation. The purpose of this study was to examine the time course of the expression of two early growth response genes, c-jun and c-fos, and of the stress response gene hsp70 after such renal injuries and to determine the role played by reactive oxygen species generated during reperfusion, on gene induction. Ischemic injury caused an almost immediate increase of c-jun, c-fos and hsp70 mRNA expression, that reached a maximum at 1 h of reperfusion. Folic acid treatment increased c-fos and hsp70 mRNAs at 2 h, while c-jun accumulated at 1 h, although to a lesser extent. The intravenous administration of two antioxidant drugs, allopurinol or dimethyl sulfoxide (DMSO), 20 min before ischemia, to prevent the generation of oxygen free radicals during reperfusion, did not cause any change in gene expression. In contrast, the combined administration of allopurinol and DMSO reduced c-jun and c-fos mRNA expression as well as tubular cell damage at 1 h of reperfusion, although not at earlier times while hsp70 mRNA expression remained almost unchanged. Taken together, the results suggest that these scavengers, by reducing reactive oxygen species and renal damage during reperfusion, may affect the expression and/or persistence of transcripts involved in the control of epithelial cell proliferation.

Acute Kidney Injury↗

PubMedDate not supplied

PKC-dependent modulation of IkB alpha-NFkB pathway in low metastatic B16F1 murine melanoma cells and in highly metastatic BL6 cells.

Protein Kinase C (PKC) is a family of at least 11 closely related isoforms with different modality of activation, and intracellular and tissue distribution. The aim of the present work was to analyse the effect of treatment with 0.1 microM TPA as well as treatment with specific inhibitors of individual PKC isoenzymes (Gö6976 for c-PKC alpha and beta isoforms and BIM for c-PKCs and n-PKCs isoforms), on the NF-kB/IkB alpha pathway in the low and high metastatic B16F1 and BL6 murine melanoma cells. The DNA-binding activity of the transcription factors AP1, AP2, CREB and OTC was also considered. Different modality of activation for NF-kB and AP1 was demonstrated in the two cell lines with the possible specific involvement of c-PKCs isoforms. In fact, in the high metastatic BL6 cells the long-term treatment for 24 hours with TPA, with no c-PKC activation or the inhibition with Gö6976 as well as with BIM, induced an increased NF-kB and AP1 DNA-binding activity. In contrast, in the low metastatic B16F1 cells the short-term treatment with TPA, induced the activation of c-PKCs isoforms, and enhanced NF-kB and AP1 DNA-binding activity. No significant changes were demonstrated for AP2, CREB and OTC DNA-binding activity in both cell lines.

Animals↗