Malic enzyme and glucose 6-phosphate dehydrogenase gene expression increases in rat liver cirrhogenesis.
The cirrhogenic ability of thioacetamide has been used to induce a model of chronic generalized liver disease that resembles the preneoplastic state of human fibrosis. Malic enzyme (ME) and glucose-6-phosphate dehydrogenase (G6PDH) are two cytosolic NADPH-generating enzymes; their activities significantly increased in liver when macronodular cirrhosis was induced by long-term thioacetamide administration to rats. The progressive increase in G6PDH and ME activities during the cirrhogenic process is parallel to the induction in gene expression of both enzymes detected by the increase in their mRNAs. These data indicate that NADPH-consuming mechanisms such as the microsomal oxidizing system and the maintenance of the cell redox state could be involved. A relationship between the extent of G6PD and ME gene expression and oxidative stress generated by the oxidative metabolism of thioacetamide is proposed as the hepatic concentration of malondialdehyde, a metabolite derived from lipid peroxidation, underwent a progressive and significant enhancement during thioacetamide-induced cirrhogenesis. These results led us to suggest that the enhanced activities of G6PDH and ME might be related to microsomal mechanisms of detoxification as well as to the maintenance of the cellular redox state. Furthermore, the noticeable increase in the hepatocyte population involved in DNA replication parallel to G6PDH activity suggests that G6PDH, through ribose-5-phosphate, might also be involved in the processes of DNA synthesis and repair.
Sanz
N
N
Instituto de Bioquímica (CSIC-UCM), Facultad de Farmacia, Madrid, Spain.
Díez-Fernández
C
C
Valverde
A M
AM
Lorenzo
M
M
Benito
M
M
Cascales
M
M
D000818:Animals; D015152:Blotting, Northern; D002273:Carcinogens; D004261:DNA Replication; D015870:Gene Expression; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics; D008291:Malate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide
D002273:Carcinogens; D012333:RNA, Messenger; D013853:Thioacetamide; D008315:Malondialdehyde; D008291:Malate Dehydrogenase; C031917:malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+); D005954:Glucosephosphate Dehydrogenase