Identification of genes enhanced by protein-calorie malnutrition by differential display polymerase chain reaction (expression of fibrinogen B beta chain, B cell translocation gene 1 and thyroid hormone responsive protein genes).
Protein-calorie malnutrition (PCM), as one of global health problems, arises during protein and/or energy deficit due to disease and nutritional inadequacy. Previously, we showed that PCM elicited oxidative stress with activation of the phase II detoxifying gene expression, which was reversed by cysteine supplementation. As part of the attempts to identify the cellular adaptive responses and the associated gene expression during PCM, the current study was initiated to analyze the genes differentially expressed in the rat during PCM. Among 1,916 bands amplified, 85 putative differentially amplified bands were enhanced by PCM in the liver, while the expression of 64 bands was suppressed. Northern and/or reverse transcription-polymerase chain reaction (RT-PCR) analyses revealed that PCM increased the expression of fibrinogen B beta chain, B cell translocation gene I (BTGI) and thyroid hormone responsive protein (THRP) mRNAs. The increase in the hepatic fibrinogen B beta chain mRNA was not prevented by cysteine supplementation, whereas cysteine decreased the enhancement in the rGSTA2 and microsomal epoxide hydrolase mRNA expression. Cysteine was also active in reversing the increase in BTG1 mRNA during PCM. This was supported by the increase in BTG1 mRNA in H4IIE cells exposed to sulfur amino acid-deprived medium. Northern blot analysis revealed that THRP, highly expressed in the brain in a tissue-specific manner, was induced by PCM and that cysteine supplementation abolished the THRP induction. Conversely, the level of hepatic albumin mRNA was markedly decreased by PCM, which was partially restored by cysteine supplementation. Differential display RT-PCR analysis allowed us to identify the genes that are responsive to oxidative stress during PCM and to characterize the differential role of cysteine on the expression of the fibrinogen B beta chain, BTG1 and THRP genes as a homeostatic adaptive response during protein deficiency.
Lee
Ae Kyung
AK
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, South Korea.
Kang
Keon Wook
KW
Kim
Yoon Gyoon
YG
Cho
Min Kyung
MK
Lee
Myung Gull
MG
Shim
Chang-Koo
CK
Chung
Suk Jae
SJ
Kim
Sang Geon
SG
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D005340:Fibrinogen / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics*; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D009928:Organ Specificity; D011502:Protein-Energy Malnutrition / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
C109099:Abi2 protein, rat; D048868:Adaptor Proteins, Signal Transducing; C115499:BBeta fibrinogen; C489553:Btg1 protein, rat; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D005340:Fibrinogen