Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.3 (HSD)
 3,464 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HL60 cells are human promyeloid cells that can be induced to differentiate by physiological stimuli (e.g. all-trans retinoic acid (ATRA), 1 alpha,25-dihydroxyvitamin D3 (D3), granulocyte colony-stimulating factor (G-CSF)) and by non-physiological agents such as dimethysulphoxide (DMSO) and protein kinase C-activating phorbol esters. The sensitivity of HL60 cells to physiological differentiating agents, but not to DMSO, is enhanced when cells are exposed to 'anti-inflammatory agents' (e.g. indomethacin) or are 'primed' (pretreated) with a small amount of ATRA: alone, neither treatment induces differentiation. We earlier suggested that indomethacin might act by inhibiting the endogenous formation of a differentiation-suppressing prostanoid (Bunce, C.M., et al. (1994) Leukemia 8, 595-604). Studies of the formation of prostanoids by HL60 cells and of the effects of prostanoids on these cells failed to identify any prostanoid that could be implicated in sensitization by indomethacin. 3 alpha-Hydroxysteroid dehydrogenase (3 alpha-HSD) is another target of such 'anti-inflammatory agents'. Steroid inhibitors of 3 alpha-HSD sensitized HL60 cells to inducers of differentiation in a manner similar to indomethacin. 3 alpha-HSD is a member of the aldoketoreductase enzyme family, which comprises many enzymes of similar size and primary sequence. A protein that was recognised by an antiserum to 3 alpha-HSD was found in HL60 cells, but the cells showed no detectable 3 alpha-HSD activity. The 3 alpha-HSD-like protein was strikingly down-regulated by 'priming' doses of ATRA. When treatment with a differentiation-sensitizing 'anti-inflammatory agent' or steroid was combined with ATRA "priming', the effects of the different treatments were not additive: the resulting increase in sensitivity equalled that achievable by either treatment alone. We conclude that interference with a single intracellular regulatory mechanism underlies the increases in sensitivity of cells to differentiating agents that are caused by anti-inflammatory agents, by certain steroids and by 'priming' with ATRA. Decreased activity of a yet-to-be-identified member of the aldoketoreductase family of dehydrogenases is likely to be a central feature of a previously unrecognised mechanism that controls the responsiveness of cells to environmental stimuli such as retinoids and D3.
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PMID:Potentiation of myeloid differentiation by anti-inflammatory agents, by steroids and by retinoic acid involves a single intracellular target, probably an enzyme of the aldoketoreductase family. 866 46

Hypersecretion of cortisol is associated with hypertension. In addition, an abnormal cortisol metabolism may play a role in the pathogenesis of hypertension. The 11beta-hydroxysteroid dehydrogenase (11beta-HSD) isozymes catalyze interconversion of cortisol and cortisone and play an important role in the regulation of the effects of cortisol. Activity of 11beta-HSD type 2, converting active cortisol in inactive cortisone, is crucial in preventing access of cortisol to the renal mineralocorticoid receptors (MRs). Decreased activity of this isozyme in the kidney, either congenitally in Apparent Mineralocorticoid Excess syndrome or acquired following licorice consumption, allows cortisol access to the MRs, resulting in hypokalemic hypertension. In normotensive subjects, an association has been demonstrated between blood pressure increase on a high-salt diet and a mild decrease of renal 11beta-HSD2 activity. In ectopic adrenocorticotropic hormone (ACTH), plasma cortisol levels are very high, resulting in mineralocorticoid hypertension caused by saturation of the available renal 11beta-HSD2 capacity. Activity of the 11beta-HSDs has also been demonstrated in many extrarenal sites. Several studies have demonstrated extrarenal effects of cortisol on blood pressure, as well as a possible role for altered extrarenal 11beta-HSD activities in the pathogenesis of hypertension. More studies are needed to clarify the role of 11beta-HSDs in the pathogenesis of hypertension.
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PMID:Cortisol, 11beta-hydroxysteroid dehydrogenases, and hypertension. 1547 32