Regulation of elongation factor-1 expression by vitamin E in diabetic rat kidneys.
Translation elongation factor-1 (EF-1) forms a primary site of regulation of protein synthesis and has been implicated amongst others in tumorigenesis, diabetes and cell death. To investigate whether diabetes-induced oxidative stress affects EF-1 gene expression, we used a free radical scavenger, vitamin E. The following groups of rats (5/group) were studied: control, vitamin E control, diabetic and diabetic treated with vitamin E. Markers of hyperglycemia, kidney function, oxidative stress, and kidney hypertrophy were elevated in diabetic rats. Increased urinary protein excretion indicated early signs of glomerular and tubular dysfunction. The mRNA and protein levels of the three EF-1 subunits (A, Balpha, and Bgamma) were determined in renal cortex extracts using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), northern blot analysis and western blotting. EF-1A mRNA expression in renal cortex extracts was significantly increased by at least 2-fold (p < 0.002) in diabetic rats; however, there was no change in the mRNA levels of EF-1Balpha and EF-1Bgamma subunits. Similar results were observed at the protein level. Treatment of diabetic rats with vitamin E for 10 days suppressed both glycemic and oxidative stresses in renal cortex and kidney hypertrophy. EF-1A mRNA and protein levels were also reduced to control levels. In conclusion, EF-1A but not EF-1Balpha and EF-1Bgamma gene expression is significantly enhanced in the renal cortex of diabetic rats. Normalization of enhanced EF-1A expression by vitamin E treatment suggests a role for EF-1A during diabetes-induced oxidative stress.
Al-Maghrebi
May
M
Department of Biochemistry, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. malmaghrebi@hsc.edu.kw
Cojocel
Constantin
C
Thompson
Mary S
MS
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D015152:Blotting, Northern; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006943:Hyperglycemia / Q000209:etiology / Q000517:prevention & control; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D020648:Peptide Elongation Factor 1 / Q000235:genetics / Q000378:metabolism*; D011507:Proteinuria / Q000503:physiopathology; D015347:RNA Probes; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000633:toxicity; D014810:Vitamin E / Q000627:therapeutic use*
D000975:Antioxidants; D001786:Blood Glucose; D020648:Peptide Elongation Factor 1; D015347:RNA Probes; D012333:RNA, Messenger; D014810:Vitamin E; D013311:Streptozocin