Hepatocytes specific genes

HBV-based vectors efficiently target quiescent hepatocytes and HBV-specific promoter and enhancer elements allow hepatocyte specific gene expression (Protzer et al. 1999). In addition, a very favorable ratio of infectious to defective particles renders HBV-based vectors good candidates for liver-directed gene transfer. Improved HBV vectors, in which HBV gene expression was abolished (Untergasser and Protzer 2004), were used in chimpanzees to treat chronic HCV infection and did not show any toxicity (Shin et al. 2005). 

Smith AJ, de Vree JM, Ottenhoff R, Oude Elferink RP, Schinkel AH, Borst P. Hepatocyte-specific expression of the human MDR3 P-glycoprotein gene restores the biliary phosphatidylcholine excretion absent in Mdr2 (-/-) mice. Hepatology 1998 28(2) 530-536. 

Okawa H, Motohashi H, Kobayashi A, Aburatani H, Kensler TW, Yamamoto M (2006) Hepatocyte-specific deletion of the keapl gene activates Nrf2 and confers potent resistance against acute drug toxicity. Biochem Biophys Res Commun 339(1 ) 79-88. doi 10.1016/j.bbrc.2005.10.185... 

Greuet, J., L. Richard, C. Bonfils, J. Domergue, and P. Maurel (1996). The fetal specific gene CYP3A7 is inducible by rifampicin in adult human hepatocytes in primary culture. Biochem. Biophys. Res. Commun. 225, 689-694. 

The thyroid gland secretes the thyroid hormones tetraiodothyronine (T4) and triiodothyronine (T3) (see Fig. 11.8 for the structure of T3). T3 is the most active form of the hormone. T4 is synthesized and secreted in approximately 10 times greater amounts than T3. Hepatocytes (liver cells) and other cells contain a deiodi-nase that removes one of the iodines from T4, converting it to T3. T3 exerts its effects on tissues by regulating the transcription of specific genes involved in energy metabolism (see Chapter 16, section III.C.2., Fig. 16.14). 

The fact that the seven pulse per day frequency of GH stimulation is ineffective for the male-specific expression of the liver enzyme indicates that a critical time interval is needed for recovery in the hepatic tissue (Waxman et al., 1991). This observation fits well with the finding that hepatocyte GH receptors in the adult rat internalize after a GH pulse and return to the membrane after a minimum of 3 h (Bick, Youdim Hochberg, 1989a,b). Increased efficiency of pulsatile versus continuous GH infusion is also observed at the cellular level, with respect to growth factor mRNA synthesis (Isgaard et al., 1988) and control of a regulator of male-specific gene expression (Waxman et al., 1995). 

Holloway MG, Cui Y, Laz EV, Hosui A, Hennighausen L, Waxman DJ (2007) Loss of sexually dimorphic liver gene expression upon hepatocyte-specific... 

Snykers, S., Henkens, T., De Rop, E. et al. 2009. Role of epigenetics in Uver-specific gene transcription, hepatocyte differentiation and stem ceU reprogrammation. / Hepatol 51 187-211. 

Zahedi K, Barone SL, Xu J, Steinbergs N, Schuster R, LentschAB, Amlal H, Wang J, Casero RA Jr, Soleimani M (2012) Hepatocyte-specific ablation of spermine/spermidine-Nl-acetyltransferase gene reduces the severity of CC14-induced acute liver injury. Am J Physiol Gastrointest Liver Physiol 303 546-560... 

Over the past years it has become apparent that the cell type is an important determinant of the extent of oxidative stress that may occur. Both the latent activities of cytoprotective enzymes in specific cell types, as well as the ability of the cell to respond rapidly to an oxidative insult by the upregulation of such enzymes, will be important predeterminants of the fate of the cell. Table 10.1 shows the concentrations of both antioxidants and cytoprotective enzymes in a variety of tissues. While the liver is well provided with antioxidant protection, the brain has very low levels, so the ability to respond rapidly to an oxidative insult by upregulation of gene transcription and translation will be an important determinant of survival or death. Cells such as hepatocytes have high levels of expression and... 

The choice of target cells is another point worthy of discussion. In some instances, this choice is predetermined, e.g. treatment of the genetic condition, familial hypercholesterolaemia, would require insertion of the gene coding for the low-density lipoprotein receptor specifically in hepatocytes. 

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