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Molecular biology of histidine decarboxylase and prostaglandin receptors.

Ichikawa A, Sugimoto Y, Tanaka S - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

Bottom Line: For the precise understanding of the physiological roles of histamine and PGs, it is necessary to clarify the molecular mechanisms involved in their synthesis as well as their receptor-mediated responses.We then characterized the expression patterns and functions of these genes.We have here summarized our research, which should contribute to progress in the molecular biology of HDC and PG receptors.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan. aichikaw@mukogawa-u.ac.jp

ABSTRACT
Histamine and prostaglandins (PGs) play a variety of physiological roles as autacoids, which function in the vicinity of their sources and maintain local homeostasis in the body. They stimulate target cells by acting on their specific receptors, which are coupled to trimeric G proteins. For the precise understanding of the physiological roles of histamine and PGs, it is necessary to clarify the molecular mechanisms involved in their synthesis as well as their receptor-mediated responses. We cloned the cDNAs for mouse L-histidine decarboxylase (HDC) and 6 mouse prostanoid receptors (4 PGE(2) receptors, PGF receptor, and PGI receptor). We then characterized the expression patterns and functions of these genes. Furthermore, we established gene-targeted mouse strains for HDC and PG receptors to explore the novel pathophysiological roles of histamine and PGs. We have here summarized our research, which should contribute to progress in the molecular biology of HDC and PG receptors.

Show MeSH
Regulation of histamine synthesis by the post-translational processing of mouse HDC. HDC is initially translated as the precursor form, with a molecular weight of 74-kDa (74-kDa HDC). Since HDC lacks the canonical signal sequence at its N-terminus, HDC appears to be post-translationally targeted to the ER in an unidentified manner. One of the processing enzymes that are responsible for the post-translational processing of HDC was found to be caspase-9. The 53-kDa form of HDC is localized mainly in the granule fraction and possesses higher enzymatic activity. On the other hand, the 74-kDa form of HDC undergoes degradation through the ubiquitin–proteasome pathway. Histamine is synthesized in the cytosol and transported into the granules by vesicular monoamine transporter-2 (VMAT2). Stored histamine is released from the granules upon various stimuli, such as IgE-mediated antigen stimulation in mast cells. Excess amounts of histamine might be exported through organic cation transporter-3 (OCT3), which is known to be a transporter for organic cations with low affinity but high capacity. The 74-kDa HDC is the dominant form in the cells lacking histamine granules, such as macrophages, whereas the 53-kDa HDC is detected in the granule-containing cells, such as mast cells and neutrophils.
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fig01: Regulation of histamine synthesis by the post-translational processing of mouse HDC. HDC is initially translated as the precursor form, with a molecular weight of 74-kDa (74-kDa HDC). Since HDC lacks the canonical signal sequence at its N-terminus, HDC appears to be post-translationally targeted to the ER in an unidentified manner. One of the processing enzymes that are responsible for the post-translational processing of HDC was found to be caspase-9. The 53-kDa form of HDC is localized mainly in the granule fraction and possesses higher enzymatic activity. On the other hand, the 74-kDa form of HDC undergoes degradation through the ubiquitin–proteasome pathway. Histamine is synthesized in the cytosol and transported into the granules by vesicular monoamine transporter-2 (VMAT2). Stored histamine is released from the granules upon various stimuli, such as IgE-mediated antigen stimulation in mast cells. Excess amounts of histamine might be exported through organic cation transporter-3 (OCT3), which is known to be a transporter for organic cations with low affinity but high capacity. The 74-kDa HDC is the dominant form in the cells lacking histamine granules, such as macrophages, whereas the 53-kDa HDC is detected in the granule-containing cells, such as mast cells and neutrophils.

Mentions: On the other hand, we also found that proteolytic cleavage of the recombinant 74-kDa protein results in its enzymatic activation.13) An increase in histamine synthesis in the stomach under repeated cold stress was accompanied by induction of proteolytic activity that could cause the post-translational processing of HDC in vitro. Recently, we identified caspase-9 as one of the processing enzymes responsible for enzymatic activation of mouse HDC in P-815 cells.32) Caspase-9-mediated cleavage of HDC was accompanied by formation of the 53-kDa species and drastic increases in its enzymatic activity. The regulation of histamine synthesis through the post-translational processing of HDC is summarized in Fig. 1.


Molecular biology of histidine decarboxylase and prostaglandin receptors.

Ichikawa A, Sugimoto Y, Tanaka S - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

Regulation of histamine synthesis by the post-translational processing of mouse HDC. HDC is initially translated as the precursor form, with a molecular weight of 74-kDa (74-kDa HDC). Since HDC lacks the canonical signal sequence at its N-terminus, HDC appears to be post-translationally targeted to the ER in an unidentified manner. One of the processing enzymes that are responsible for the post-translational processing of HDC was found to be caspase-9. The 53-kDa form of HDC is localized mainly in the granule fraction and possesses higher enzymatic activity. On the other hand, the 74-kDa form of HDC undergoes degradation through the ubiquitin–proteasome pathway. Histamine is synthesized in the cytosol and transported into the granules by vesicular monoamine transporter-2 (VMAT2). Stored histamine is released from the granules upon various stimuli, such as IgE-mediated antigen stimulation in mast cells. Excess amounts of histamine might be exported through organic cation transporter-3 (OCT3), which is known to be a transporter for organic cations with low affinity but high capacity. The 74-kDa HDC is the dominant form in the cells lacking histamine granules, such as macrophages, whereas the 53-kDa HDC is detected in the granule-containing cells, such as mast cells and neutrophils.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3037517&req=5

fig01: Regulation of histamine synthesis by the post-translational processing of mouse HDC. HDC is initially translated as the precursor form, with a molecular weight of 74-kDa (74-kDa HDC). Since HDC lacks the canonical signal sequence at its N-terminus, HDC appears to be post-translationally targeted to the ER in an unidentified manner. One of the processing enzymes that are responsible for the post-translational processing of HDC was found to be caspase-9. The 53-kDa form of HDC is localized mainly in the granule fraction and possesses higher enzymatic activity. On the other hand, the 74-kDa form of HDC undergoes degradation through the ubiquitin–proteasome pathway. Histamine is synthesized in the cytosol and transported into the granules by vesicular monoamine transporter-2 (VMAT2). Stored histamine is released from the granules upon various stimuli, such as IgE-mediated antigen stimulation in mast cells. Excess amounts of histamine might be exported through organic cation transporter-3 (OCT3), which is known to be a transporter for organic cations with low affinity but high capacity. The 74-kDa HDC is the dominant form in the cells lacking histamine granules, such as macrophages, whereas the 53-kDa HDC is detected in the granule-containing cells, such as mast cells and neutrophils.
Mentions: On the other hand, we also found that proteolytic cleavage of the recombinant 74-kDa protein results in its enzymatic activation.13) An increase in histamine synthesis in the stomach under repeated cold stress was accompanied by induction of proteolytic activity that could cause the post-translational processing of HDC in vitro. Recently, we identified caspase-9 as one of the processing enzymes responsible for enzymatic activation of mouse HDC in P-815 cells.32) Caspase-9-mediated cleavage of HDC was accompanied by formation of the 53-kDa species and drastic increases in its enzymatic activity. The regulation of histamine synthesis through the post-translational processing of HDC is summarized in Fig. 1.

Bottom Line: For the precise understanding of the physiological roles of histamine and PGs, it is necessary to clarify the molecular mechanisms involved in their synthesis as well as their receptor-mediated responses.We then characterized the expression patterns and functions of these genes.We have here summarized our research, which should contribute to progress in the molecular biology of HDC and PG receptors.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan. aichikaw@mukogawa-u.ac.jp

ABSTRACT
Histamine and prostaglandins (PGs) play a variety of physiological roles as autacoids, which function in the vicinity of their sources and maintain local homeostasis in the body. They stimulate target cells by acting on their specific receptors, which are coupled to trimeric G proteins. For the precise understanding of the physiological roles of histamine and PGs, it is necessary to clarify the molecular mechanisms involved in their synthesis as well as their receptor-mediated responses. We cloned the cDNAs for mouse L-histidine decarboxylase (HDC) and 6 mouse prostanoid receptors (4 PGE(2) receptors, PGF receptor, and PGI receptor). We then characterized the expression patterns and functions of these genes. Furthermore, we established gene-targeted mouse strains for HDC and PG receptors to explore the novel pathophysiological roles of histamine and PGs. We have here summarized our research, which should contribute to progress in the molecular biology of HDC and PG receptors.

Show MeSH