Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.26.9 (
ribonuclease
)
6,589
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In humans the last steps in the synthesis of aldosterone and cortisol rely on the activity of two cytochrome P450 genes termed CYP11B2 (aldosterone synthase;
P450aldo
) and CYP11B1 (11 beta hydroxylase; P450cl1). The mechanisms which lead to differential expression of these two genes within the adrenal cortex are not well-defined. The human adrenocortical cell line. H295R, was utilized in this study to examine the intracellular second messenger pathways regulating expression of
P450aldo
and P450c11. using specific
ribonuclease
protection assays. Treatment of H295R cells with angiotensin II or potassium (K+) caused a time-dependent induction in the level of
P450aldo
transcripts. While K+ treatment was more specific for the induction of
P450aldo
mRNA, treatment with angiotensin II increased levels of both
P450aldo
and P450c11 transcripts. To define the second messenger systems which influence transcript levels for these enzymes, the effects of agonists of the protein kinase A, protein kinase C, and calcium pathways were tested on the expression of
P450aldo
and P450c11. Activation of the protein kinase A pathway by the agonists, dibutyryl cAMP or forskolin, preferentially increased the P450c11 transcript to a greater degree than
P450aldo
. Interestingly, activation of the protein kinase C pathway by tetradecanoylphorbol acetate (TPA) did not alter transcripts for either
P450aldo
or P450c11. The calcium channel agonist BAYK 8644 mimicked the effects of K+ by increasing the transcript for
P450aldo
. However, the calcium channel blocker nifedipine attenuated the stimulatory effects of angiotensin II and K+ on the levels of
P450aldo
. However, the calcium channel blocker nifedipine attenuated the stimulatory effects of angiotensin II and K+ on the levels of
P450aldo
transcripts without affecting the stimulatory effect of dbcAMP. This study demonstrates that the protein kinase A pathway preferentially induces P450c11 mRNA over that of
P450aldo
. In addition, pharmacologic agents that affect calcium levels provide evidence for an additional regulatory mechanism in modulating the expression of
P450aldo
. This is of importance since the major physiologic regulators of aldosterone secretion, angiotensin II and K+ are able to increase intracellular calcium but have little effect on intracellular cAMP levels.
...
PMID:Differential regulation of 11 beta-hydroxylase and aldosterone synthase in human adrenocortical H295R cells. 886 69
