title: Effect of aging on norepinephrine-related proliferative response in primary cultured periportal and perivenous hepatocytes.
abstract: Norepinephrine (NE) amplifies the mitogenic effect of EGF in a rat liver through the adrenergic receptor coupled with G protein, Ghα. Ghα is also known as a transglutaminase 2 (TG2), whose cross-linking activity is implicated in hepatocyte growth. Recently, we found that NE-induced amplification of EGF-induced DNA synthesis in hepatocytes obtained from perivenous regions of liver is caused by inhibiting the downregulation of EGF receptor (EGFR) by TG2. In the present study, we investigated the effect of aging on NE-related proliferative response. Hepatocytes were obtained from the liver of 7- and 90-wk-old rats. To examine this in detail, periportal hepatocytes (PPH) and perivenous hepatocytes (PVH) were isolated using the digitonin/collagenase perfusion technique. EGF or NE receptor binding was analyzed by Scatchard analysis. Changes in NE-induced DNA synthesis, G protein activity, and TG2 activity were measured. NE slightly potentiated [125I]EGF binding to EGFR, and EGF-induced DNA synthesis in PVH but not in PPH. [3H]NE binding studies indicated that PVH have a greater number of receptors than PPH, and that the number of receptors in both subpopulations increased with aging. NE-induced changes in G protein activity and TG2 activity in 90-wk-old rats were slight compared with 7-wk-old rats. These results suggest that NE results in a slight recovery effect on the age-related decline in EGF-induced DNA synthesis because of incomplete switching of the function from TG2 to Ghα.
authors: Department of Radiopharmacy, Tohoku Pharmaceutical University, 4-4-1, Komatsushima, Aoba-ku, Sendai, Miyagi 981-8558, Japan.
authors: Tomonori
authors: T
authors: Kobayashi
authors: Yohei
authors: Y
authors: Saito
authors: Yosuke
authors: Y
authors: Ohtake
authors: Akiko
authors: A
authors: Maruko
authors: Yumi
authors: Y
authors: Yamamoto
authors: Fumihiko
authors: F
authors: Yamamoto
authors: Yoshikazu
authors: Y
authors: Kuwahara
authors: Motoi
authors: M
authors: Fukumoto
authors: Manabu
authors: M
authors: Fukumoto
authors: Yasuhito
authors: Y
authors: Ohkubo
mesh_terms: D000367:Age Factors; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D004261:DNA Replication; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D022781:Hepatocytes / Q000502:physiology*; D009638:Norepinephrine / Q000235:genetics / Q000378:metabolism; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000235:genetics / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism*
chemical_list: D011941:Receptors, Adrenergic; C000717609:Tgm2 protein, rat; D004815:Epidermal Growth Factor; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D066246:ErbB Receptors; D019204:GTP-Binding Proteins; D009638:Norepinephrine