Glucose regulation of CDK7, a putative thiol related gene, in experimental diabetic nephropathy.
We previously described the identification of the 3'end of an unknown gene CDK7 using differential display which appeared to be up-regulated in diabetic kidneys [R.A. Page, C.A. Morris, J.D. Williams, C.J. von Ruhland, A.N. Malik, Isolation of diabetes-associated kidney genes using differential display, Biochem. Biophys. Res. Commun. 232 (1997) 49-53]. Here we show that CDK7 is a putative thiol related gene which is regulated by glucose in human and rat renal cells. CDK7 mRNA increased by >threefold in cultured human mesangial cells grown in high glucose for 4 days. In the kidneys of the GK rat, a model of type II diabetes, CDK7 showed a steady age-related increase in mRNA, increasing to >sixfold in 40 week GK rats compared to normoglycemic age-matched Wistar rat kidneys, this increase correlates with progressive hyperglycemia. CDK7 mRNA is widely expressed, showing particularly high levels of expression in rat and human liver, and encodes a putative 338 amino acids highly conserved peptide with several conserved domains, including a cys-pro-arg-cys domain conserved in 15 diverse species which is similar to the catalytic centre of thioredoxin, suggesting a role in oxidative stress.
Malik
Afshan N
AN
Division of Reproduction and Endocrinology, School of Biomedical and Health Sciences, King's College London, UK. afshan.malik@kcl.ac.uk
Rossios
Christos
C
Al-Kafaji
Ghada
G
Shah
Akram
A
Page
Rachel A
RA
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D018844:Cyclin-Dependent Kinases / Q000737:chemistry / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D000095043:Cyclin-Dependent Kinase-Activating Kinase
D013438:Sulfhydryl Compounds; D018844:Cyclin-Dependent Kinases; D005947:Glucose; D000095043:Cyclin-Dependent Kinase-Activating Kinase