Chromosomal localization of the type-I 15-PGDH gene to 4q34-q35

Pichaud, Franck; Delage-Mourroux, Régis; Pidoux, E.; Jullienne, A.; Rousseau-Merck, Marie-Françoise

doi:10.1007/s004390050354

Cited by 20 publications

(14 citation statements)

References 9 publications

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“…The mouse gene is 11.3 kb in length [29], whereas the human gene is 31 kb [30]. The human gene is localized to 4q34-q35 [31]. Both mouse and human genes contain seven exons and 6 introns.…”

Section: Introductionmentioning

confidence: 99%

NAD+-Linked 15-Hydroxyprostaglandin Dehydrogenase: Structure and Biological Functions

Tai¹,

Cho²,

Tong³

et al. 2006

CPD

118

108

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NAD(+)-linked 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the oxidation of 15(S)-hydroxyl group of prostaglandins and lipoxins resulting in the formation of 15-keto metabolites which exhibit greatly reduced biological activities. Therefore, this enzyme has been considered the key enzyme responsible for the inactivation of prostaglandins and lipoxins. Both the cDNA and the genomic DNA of the 15-PGDH gene have been cloned. Structural characterization, transcriptional regulation and biological functions of this enzyme have been investigated. Molecular modeling corroborated with site-directed mutagenesis has identified key residues and domains involved in coenzyme and substrate binding. Catalytic mechanism has been proposed. Studies on the regulation of enzyme expression and activity by physiological and pharmacological agents have begun to uncover its significant roles in cancer, inflammation and reproduction. Apparently, 15-PGDH works with cyclooxygenase-2 to control the cellular levels of prostaglandins. Their reciprocal regulation within the same cells appears to determine the fate of the cells. Because of its ability to inactivate both prostaglandins and lipoxins of two opposite biological activities, the roles of 15-PGDH in cancer and inflammation are particularly intriguing and challenging. Future investigations in these areas are warranted.

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“…The mouse gene is 11.3 kb in length [29], whereas the human gene is 31 kb [30]. The human gene is localized to 4q34-q35 [31]. Both mouse and human genes contain seven exons and 6 introns.…”

Section: Introductionmentioning

confidence: 99%

NAD+-Linked 15-Hydroxyprostaglandin Dehydrogenase: Structure and Biological Functions

Tai¹,

Cho²,

Tong³

et al. 2006

CPD

118

108

View full text Add to dashboard Cite

show abstract

“…The key enzyme responsible for metabolic inactivation of prostaglandins, including PGE 2 , is NAD ϩ -dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) (38). The human gene is located on chromosome 4 and codes for a 29-kDa enzyme that catalyzes the formation of 15-ketoprostaglandins (30,38). 15-Ketoprostaglandins possess greatly reduced biological activities.…”

mentioning

confidence: 99%

Levels of NAD⁺-dependent 15-hydroxyprostaglandin dehydrogenase are reduced in inflammatory bowel disease: evidence for involvement of TNF-α

Otani¹,

Yamaguchi²,

Scherl³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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Increased amounts of PGE(2) have been detected in the inflamed mucosa of patients with inflammatory bowel disease (IBD). This increase has been attributed to enhanced synthesis rather than reduced catabolism of PGE(2). 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) plays a major role in the catabolism of PGE(2). In this study, we investigated whether amounts of 15-PGDH were altered in inflamed mucosa from patients with IBD. Amounts of 15-PGDH protein and mRNA were markedly reduced in inflamed mucosa from patients with Crohn's disease and ulcerative colitis. In situ hybridization demonstrated that 15-PGDH was expressed in normal colonic epithelium but was virtually absent in inflamed colonic mucosa from IBD patients. Because of the importance of TNF-alpha in IBD, we also determined the effects of TNF-alpha on the expression of 15-PGDH in vitro. Treatment with TNF-alpha suppressed the transcription of 15-PGDH in human colonocytes, resulting in reduced amounts of 15-PGDH mRNA and protein and enzyme activity. In contrast, TNF-alpha induced two enzymes (cyclooxygenase-2 and microsomal prostaglandin E synthase-1) that contribute to increased synthesis of PGE(2). Overexpressing 15-PGDH blocked the increase in PGE(2) production mediated by TNF-alpha. Taken together, these results suggest that reduced expression of 15-PGDH contributes to the elevated levels of PGE(2) found in inflamed mucosa of IBD patients. The decrease in amounts of 15-PGDH in inflamed mucosa can be explained at least, in part, by TNF-alpha-mediated suppression of 15-PGDH transcription.

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“…It has been proposed that two major steps are involved in prostaglandin inactivation: uptake from the plasma membrane by prostaglandin transporters and oxidation by NAD ϩ -dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) (21,22,34). Pichaud et al (24) noted that 15-PGDH is the main enzyme of prostaglandin degradation. By catalyzing the conversion of the 15-hydroxyl group of prostaglandins into a keto group, this ubiquitous enzyme strongly reduces the biological activity of these molecules (24).…”

Section: Prostaglandins (Pgs)mentioning

confidence: 99%

“…Pichaud et al (24) noted that 15-PGDH is the main enzyme of prostaglandin degradation. By catalyzing the conversion of the 15-hydroxyl group of prostaglandins into a keto group, this ubiquitous enzyme strongly reduces the biological activity of these molecules (24). Previous reports have shown that 15-PGDH was expressed in the proximal tubule, cortical, and outer medullary thick ascending limb, and collecting duct of the kidney but not in the macula densa or papilla (41).…”

Section: Prostaglandins (Pgs)mentioning

confidence: 99%

Postnatal regulation of 15-hydroxyprostaglandin dehydrogenase in the rat kidney

Liu

Sun

Zhou

et al. 2014

American Journal of Physiology-Renal Physiology

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Cyclooxygenase 2 (COX-2) has an established role in postnatal kidney development. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is recently identified as an endogenous inhibitor of COX-2, limiting the production of COX-2-derived prostanoids in several pathological conditions. The present study was undertaken to examine the regulation of renal 15-PGDH expression during postnatal kidney development in rats compared with COX-2. qRT-PCR and immunoblotting demonstrated that 15-PGDH mRNA and protein in the kidney were present in neonates, peaked in the second postnatal week, and then declined sharply to very low level in adulthood. Immunostaining demonstrated that at the second postnatal week, renal 15-PGDH protein was predominantly found in the proximal tubules stained positive for Na/H exchanger 3 and brush borders (periodic acid-Schiff), whereas COX-2 protein was restricted to macular densa and adjacent thick ascending limbs. Interestingly, in the fourth postnatal week, 15-PGDH protein was redistributed to thick ascending limbs stained positive for the Na-K-2Cl cotransporter. After 6 wk of age, 15-PGDH protein was found in the granules in subsets of the proximal tubules. Overall, these results support a possibility that 15-PGDH may regulate postnatal kidney development through interaction with COX-2.

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Chromosomal localization of the type-I 15-PGDH gene to 4q34-q35

Cited by 20 publications

References 9 publications

NAD+-Linked 15-Hydroxyprostaglandin Dehydrogenase: Structure and Biological Functions

NAD+-Linked 15-Hydroxyprostaglandin Dehydrogenase: Structure and Biological Functions

Levels of NAD⁺-dependent 15-hydroxyprostaglandin dehydrogenase are reduced in inflammatory bowel disease: evidence for involvement of TNF-α

Postnatal regulation of 15-hydroxyprostaglandin dehydrogenase in the rat kidney

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Chromosomal localization of the type-I 15-PGDH gene to 4q34-q35

Cited by 20 publications

References 9 publications

NAD+-Linked 15-Hydroxyprostaglandin Dehydrogenase: Structure and Biological Functions

NAD+-Linked 15-Hydroxyprostaglandin Dehydrogenase: Structure and Biological Functions

Levels of NAD+-dependent 15-hydroxyprostaglandin dehydrogenase are reduced in inflammatory bowel disease: evidence for involvement of TNF-α

Postnatal regulation of 15-hydroxyprostaglandin dehydrogenase in the rat kidney

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Levels of NAD⁺-dependent 15-hydroxyprostaglandin dehydrogenase are reduced in inflammatory bowel disease: evidence for involvement of TNF-α