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:4.1.1.17 (
ornithine decarboxylase
)
6,351
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
To elucidate the role of polyamine metabolism in the regulation of mesangial cell growth, we examined the involvement of
ornithine decarboxylase
(
ODC
), the rate limiting enzyme for polyamine synthesis, in the mitogenesis of cultured rat mesangial cells (MCs). Resting MCs, stimulated with fetal calf serum (FCS 10%), showed an induction of
ODC
activity from undetectable values in resting cells to mean = 5035 nmol CO2/10(10) cells.hr (range 3157 to 7154, N = 5), which is 25-fold above the detection limit. We found a single peak of
ODC
activity eight to ten hours after stimulation, declining to 22 to 34% of peak levels after 24 hours. 3H-thymidine (TdR) uptake, an S-phase marker of MC replication, peaked at 24 hours, reaching 10.7-fold values of resting MCs.
ODC
mRNA levels were low in resting cells. After serum stimulation there was a two- to 10-fold increase in
ODC
mRNA with a maximum after six hours.
ODC
activity with similar kinetics but lower peak levels was also induced by incubating MCs with mitogens, such as platelet-derived growth factor (PDGF-AB 20 ng/ml),
arginine vasopressin
(AVP 10(-7) M), phorbol myristate acetate (PMA 10(-7) M), interleukin 1 alpha and beta (IL-1 alpha 10 U/ml, IL-1 beta 10 U/ml). In the presence of alpha-difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of
ODC
, the growth rate of MCs, assessed by cell counts and by 3H-TdR uptake, was markedly reduced by 62 to 100%. This antiproliferative effect of DFMO could be reversed by addition of putrescine, the reaction product of
ODC
.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Role of ornithine decarboxylase for proliferation of mesangial cells in culture. 174 18
Previous studies have indicated that
ornithine decarboxylase
(
ODC
) may be involved in the stimulation of Na+/K(+)-ATPase activity by
arginine vasopressin
(
AVP
) in the rat renal medullary thick ascending limb of Henle's loop. The present study was aimed at establishing the role of the polyamines, the conversion products of
ODC
activity, in the stimulation of Na+/K(+)-ATPase by
AVP
. Using cytochemical methods, we have demonstrated an increase in Na+/K(+)-ATPase activity after stimulation with putrescine, spermidine and spermine (each 1 mmol/l) for 2.5, 2 and 1.5 min respectively. The specific inhibitors of spermidine and spermine synthase, bis-cyclohexylammonium sulphate and N-alkylated-1,3-diaminopropane respectively, inhibited the stimulation of Na+/K(+)-ATPase by
AVP
, this inhibition being reversed by spermine. These findings suggest that polyamines are involved in the stimulus-response coupling of the hormone-mediated response.
...
PMID:Stimulation of Na+/K(+)-ATPase activity by polyamines in the rat renal medullary cells of the thick ascending limb of Henle's loop. 217 62
The effect of
arginine vasopressin
(
AVP
) on rat renal
ornithine decarboxylase
(
ODC
) activity was investigated by a cytochemical technique optimized for use in the medullary thick ascending limb of Henle's loop (mTAL). Stimulation of
ODC
activity by
AVP
was confined to the mTAL. Peaks in enzyme activity in cultured rat renal segments occurred after tissue had been exposed to
AVP
for 3 or 8 min and these times of maximal stimulation did not change with the concentration of
AVP
. There was a dose-dependent response in
ODC
activity over the
AVP
concentration range 0.01 10 fmol/l. The
ODC
response to
AVP
was totally blocked by specific antiserum to
AVP
and reduced by 70% with the specific inhibitor to
ODC
, difluoromethyl ornithine.
...
PMID:Stimulation of ornithine decarboxylase activity by arginine vasopressin in the rat medullary thick ascending limb of Henle's loop. 249 81
Prior exposure of immature rat testis to
arginine vasopressin
caused the testis refractory at 24 h in terms of
ornithine decarboxylase
activity. Arginine vasopressin caused desensitization both in Leydig cells and seminiferous tubules. Arginine vasopressin induced desensitization was found to be both time and dose-dependent. Arginine vasopressin desensitized testis was refractory to luteinizing hormone, follicle stimulating hormone, norepinephrine, dibutyryl cAMP, phorbol-myristate acetate and cholera toxin at 24 h. Arginine vasopressin desensitized testis showed recovery of response to norepinephrine at 48 h after the first injection. On the contrary
arginine vasopressin
could stimulate
ornithine decarboxylase
in luteinizing hormone desensitized testis. These results indicate that in
arginine vasopressin
desensitized testis the block is at post cAMP step which is common to both cAMP dependent and protein kinase C-diacylglycerol system in stimulating testicular
ornithine decarboxylase
.
...
PMID:Desensitization of immature rat testicular ornithine decarboxylase to arginine vasopressin. 282 80
Intratesticular injection with
arginine vasopressin
caused stimulation of
ornithine decarboxylase
activity in the testes of immature rats. The increase in
ornithine decarboxylase
activity in response to
arginine vasopressin
was dose and time dependent. Maximal stimulation of
ornithine decarboxylase
activity occurred at 2 h after injection with 0.1 micrograms of
arginine vasopressin
. It was observed that stimulation of
ornithine decarboxylase
activity occurred in seminiferous tubules and in Leydig cells of the testis in response to
arginine vasopressin
.
...
PMID:Stimulation of testicular ornithine decarboxylase activity by arginine vasopressin. 375 2
Testosterone injection caused a 2,000% increase in renal
ornithine decarboxylase
activity in intact male mice. A single injection of testosterone produced the same effect as repeated injections. The response was dose-dependent and could be blocked by actinomycin, diaminopropane, and cadaverine. Cycloheximide and putrescine had no inhibitory effect. Renal ODC response to
arginine vasopressin
was altered after castration; however, urine specific gravity and serum osmolality were unaffected by changes in renal
ornithine decarboxylase
activity.
...
PMID:Effects of testosterone on renal ornithine decarboxylase and kidney function. 617 15
The polyamines spermidine and spermine are small cations present in all living cells. In the brain, these cations are particularly abundant in the neurons of the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus, which synthesize the neuropeptide hormones
arginine vasopressin
(
AVP
) and oxytocin. We recently reported increased mRNA expression of antizyme inhibitor 1 (Azin1), an important regulator of polyamine synthesis, in rat SON and PVN as a consequence of 3 days of dehydration. Here we show that AZIN1 protein is highly expressed in both
AVP
- and oxytocin-positive magnocellular neurons of the SON and PVN together with antizyme 1 (AZ1),
ornithine decarboxylase
, and polyamines. Azin1 mRNA expression increased in the SON and PVN as a consequence of dehydration, salt loading, and acute hypertonic stress. In organotypic hypothalamic cultures, addition of the irreversible
ornithine decarboxylase
inhibitor DL-2-(difluoromethyl)-ornithine hydrochloride significantly increased the abundance of heteronuclear
AVP
but not heteronuclear oxytocin. To identify the function of Azin1 in vivo, lentiviral vectors that either overexpress or knock down Azin1 were stereotaxically delivered into the SON and/or PVN. Azin1 short hairpin RNA delivery resulted in decreased plasma osmolality and had a significant effect on food intake. The expression of
AVP
mRNA was also significantly increased in the SON by Azin1 short hairpin RNA. In contrast, Azin1 overexpression in the SON decreased
AVP
mRNA expression. We have therefore identified AZIN1, and hence by inference, polyamines as novel regulators of the expression of the
AVP
gene.
...
PMID:Control of Polyamine Biosynthesis by Antizyme Inhibitor 1 Is Important for Transcriptional Regulation of Arginine Vasopressin in the Male Rat Hypothalamus. 2618 58