Assessment of the function of the betaC-subunit of activin in cultured hepatocytes.
We assessed the function of the beta(C)-subunit of activin in hepatocytes. We studied the effect of conditioned medium of Chinese hamster ovary (CHO) cell line stably expressing the beta(C) gene (CHO-beta(C)) on growth of AML12 hepatocytes. We also examined the effect of recombinant activin C and transfection of the beta(C) gene by using adenovirus vector. CHO-beta(C) secreted activin C, a homodimer of the beta(C), as well as precursors of the beta(C). The conditioned medium of CHO-beta(C) increased both [(3)H]thymidine incorporation and the cell number in AML12 cells. It also supported survival of AML12 cells in a serum-free condition. Recombinant human activin C also increased both [(3)H]thymidine incorporation and the number of AML12 cells. Transfection of AML12 cells with the beta(C)-subunit led to the stimulation of [(3)H]thymidine incorporation. Analysis of the conditioned medium revealed that the beta(C)-subunit formed a heterodimer with the endogenous beta(A), the formation of which was dependent on the amount of beta(C) expressed. Recombinant activin C did not affect the binding of (125)I-activin A to its receptor or follistatin. These results indicate that activin C stimulates growth of AML12 cells. The beta(C)-subunit modifies the function of the beta(A)-subunit by multiple mechanisms.
Wada
Wataru
W
Institute for Molecular and Cellular Regulation, Gunma University, Japan.
Maeshima
Akito
A
Zhang
You-Qing
YQ
Hasegawa
Yoshihisa
Y
Kuwano
Hiroyuki
H
Kojima
Itaru
I
D000818:Animals; D016466:CHO Cells / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D017077:Culture Media, Conditioned / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D028322:Inhibin-beta Subunits / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D011487:Protein Conformation; D011994:Recombinant Proteins; D014162:Transfection
D017077:Culture Media, Conditioned; C504186:INHBC protein, human; C504187:Inhbc protein, mouse; D011994:Recombinant Proteins; D028322:Inhibin-beta Subunits