Localization of human sulfotransferases

It is believed that knowing the expression pattern and cellular distribution of SULTs, along with the functional and structural information, will assist with determining the physical and functional significance of SULTs. To better understand the role of individual SULT isoforms in the regulation of various biological processes, a comprehensive study of cellular distribution of these enzymes in vivo is needed. Here an inclusive information has been studied in an attempt to illustrate the organ-specific distribution of individual SULT isoforms at mRNA and protein level (Table 3), and moreover, it may provide a useful information for further investigation of the physiological function of these enzymes.

2.1 SULT1A subfamily

SULT1A1 exhibits the highest expression level among all SULT1 isoforms in the liver.

It has also been identified in brain, intestine, breast, endometrium, adrenal gland, placenta, jejunum, platelets, as well as kidney and lung. SULT1A3 is highly expressed in the jejunum and placenta with the exception of adult human liver. For the developmental perspective, a significant level of expression of both SULT1A1 and SULT1A3 appeared in the fetal liver, intriguingly, SULT1A3 nearly disappears in adult kidney and liver. The cellular localization and physiological significance of SULT1A2 is the least understood among the SULT1A members. Dooley et al. (2000) had shown the SULT1A2 encoding mRNA is present in the

liver, brain, kidney, ovary, lung, and gastrointestinal tract (GI) at the lower level. However, it appears that SULT1A2 mRNA expression does not translate into the formation of protein (Gamage et al., 2006).

2.2 SULT1B subfamily

The predominant physical function of SULT1B1 appears to be in the regulation and biotransformation of thyroid hormones. Intriguingly, a significant expression of SULT1B1 mRNA and protein has been detected in the small intestine, colon, and is also found in liver and blood leukocytes at lower levels (Teubner et al., 1998; Wang et al., 1998).

2.3 SULT1C subfamily

The biological function of SULT1C is barely understood. Previous studies have indicated the presence of SULT1C2 in adult human kidney, stomach, thyroid, as well as fetal kidney and liver. It was also demonstrated that SULT1C2 protein was clearly detectable in stomach, ileum, jejunum, rectum, and cecum (Coughtrie, 2002). At the RNA level, the abundant expression of SULT1C4 was observed in fetal kidney and lung, as well as in the adult spinal cord, kidney, and ovary. However, the protein expression of SULT1C4 has not yet been demonstrated in any adult or fetal organisms or tissues (Sakakibara et al.

1998b).

2.4 SULT1E subfamily

SULT1E1 protein was detected in liver (Forbes-Bamforth and Coughtrie, 1994;

Falany et al. 1995), endometrium (Falany et al. 1998), jejunum (Her et al. 1996), and mammary epithelial cells in primary culture (Falany and Falany, 1996). The significant level of mRNA encoding SULT1E1 on the immunoblots has been demonstrated in both human liver and jejunum cytosol, and mammary epithelial cells in primary culture (Forbes-Bamforth and Coughtrie, 1994; Falany et al., 1995). The enzymatic activity of SULT1E1 was also assessed by using β-estrogen as a substrate in the different human organs, such as fetal liver, kidney, lung (Adjei et al., 2008).

.

2.5 SULT2A subfamily

Northern analysis has shown SULT2A1 is extensively present in many human tissues, such as liver, adrenal, small intestine, ovary, prostate, lover, stomach, small intestine, colon, as well as brain and bone marrow (Otterness et al., 1992; Tashiro et al., 2000). The immunohistochemical study has revealed that SULT2A1 is selectively expressed in the embryonic human hepatocytes and around the central vein (Baker et al., 1994). Paker et al.

(1994) also reported that SULT2A1 expression was detected in the fetal and neocortical zones of the adrenal cortex, liver, testis, and intestine. Further, kidney SULT2A1 immunostaining was present in the proximal and distal tubules, loops of Henle, collecting

ducts, and their progenitors (Baker et al., 1994). Despite the localization of SULT2A1 were inclusively investigated, the comprehensively physiological implication of this isozyme remains ambiguous in vivo, suggesting a simple and convenient genetic model might be needed for the further investigation.

2.6 SULT2B subfamily

Both SULT2B isoforms mRNAs have been detected in many tissues including adrenal gland, placenta, ovary, prostate, lung, kidney, colon and skin (Her et al., 1998; Dooley et al., 2000; Meloche and Falany, 2001; Javitt et al., 2001; Geese and Raftogianis, 2001). Further, the results demonstrated that SULT1Bb was more extensively expressed than SULT1Ba in a variety of hormone-responsive tissues, such as stomach, small intestine, spleen, thymus, thyroid, and liver (Geese and Raftogianis, 2001). Additionally, the protein expression of SULT1Bb is present in prostate and lung, whereas SULT1Ba is present in prostate and placenta (Geese and Raftogianis, 2001).

2.7 SULT4A subfamily

SULT4A1 is also termed “brain sulfotransferase”, which sharing an extremely high degree of sequence homology (97% amino acid identity) with the orthologous rat and mouse SULTs (Blanchard et al., 2004). Immunohistochemical staining of human brain

sections showed that SULT4A1 is located extensively, but exclusively, in a variety of brain regions including cerebral cortex (motor, cingulate, arontal), globus pallidus, medial temporal lobe (island of Calleja), amygdala pituitary, thalamus, cerebellum (dentate nucleus folia: vermis, granular layer), midbrain (oculomotor, red nucleus, magnocellular), and brainstem (Liyou et al., 2003). At present, the physiological substrate of SULT4A1 remains unknown.

2.8 TPST subfamily

TPSTs reside in the Golgi compartment and therefore have access to generate the posttranslational modification of secretory and membrane proteins transported through the trans-Golgi network (Kehoe and Bertozzi, 2000; Monigatti et al., 2006). Northern analysis

has demonstrated that both human TPST1 and TPST2 are broadly expressed in many tissues including cerebellum, fetal brain, trachea, testis, spinal cord, thyroid gland, uterus, lung, kidney, salivary gland, prostate, skeletal muscle and uterus (Ouyang et al., 1998; Mishiro et al., 2006). However, due to the lack of the isoenzyme-specific antibodies or suitable analytic reagents and probes, the cellular distribution and related abundance of TPST isoforms at the protein level have not yet been studied.

Table 3. Tissue-specific distribution of human cytosolic SULTs and TPST isoforms

Tissue-specific expression Name Chromosome Amino acids

mRNA level Protein expression SULT1A1 16p12.1 295 Epithelial cells within stomach, gastricpits, colon, crypts of

small intestine

Very high in liver; brain, breast, intestine, endometrium, adrenal gland, platelets, placenta, kidney, lung, jejunum

SULT1A2 16p12.1 295 Liver, kidney, brain, lung, ovary, GI -*

SULT1A3 16p11.2 295 Epithelial cells within stomach, gastricpits, colon, and crypts of small intestine

Very high in jejunum and colon; intestine, platelets, placenta, brain

SULT1B1 4q13.3 296 Liver, small intestine, colon, blood leukocytes Highest expression observed in colon; also detected in liver and small intestine

SULT1C2 2q11.1-q11.2 296 Adult stomach, kidney, thyroid; fetal kidney > fetal heart,

kidney, ovary, spinal cord Stomach, ileum, jejunum, rectum, cecum SULT1C4 2q11.1-q11.2 302 Adult kidney, ovary, spinal cord; fetal lung, kidney, heart -

SULT1E1 4q13.1 294 Liver, kidney, lung, adrenal gland, intestine Liver, endometrium, GI, trachea, pancreas SULT2A1 19q13.3 285 Adrenal gland, ovary, prostate, lover, stomach, small

intestine, colon, brain, bone marrow

Liver, adrenal, duodenum, central vein, brain e.g.

thalamus, hypothalamus SULT2B1a 19q13.3 350 Adrenal gland, placenta, ovary, prostate, lung, kidney, colon Prostate, placenta SULT2B1b 19q13.3 365 Adrenal gland, placenta, ovary, prostate, lung, kidney,

colon, stomach, small intestine, spleen, thymus, thyroid

Prostate, lung

SULT4A1 22q13.2-q13.31 284 Cerebral cortex, frontal lobe, cerebellum, occipital lobe, temporal lobe, medulla, putamen, lowest in the spinal cord

Brain e.g. cerebral cortex, medial temporal lobe, amygdale pituitary, thalamus, hypothalamus, midbrain, cerebellum, lentiform nucleus,

(Continued)

*Related study is currently not available.

TPST1 7q11.21 370 Cerebellum, fetal brain, trachea, testis, spinal cord, thyroid gland, uterus, lung, kidney, salivary gland, prostate, skeletal muscle, uterus

-

TPST2 22q12.1 377 Cerebellum, fetal brain, trachea, testis, spinal cord, thyroid gland, uterus, lung, kidney, salivary gland, prostate, skeletal muscle, uterus

-