Effects of natriuretic peptides (ANP, BNP, CNP) on catecholamine synthesis and TH mRNA levels in PC12 cells

Life Sciences ◽  
2000 ◽  
Vol 66 (22) ◽  
pp. PL303-PL311 ◽  
Author(s):  
Kazuhiro Takekoshi ◽  
Kiyoaki Ishii ◽  
Kazumasa Isobe ◽  
Fumio Nomura ◽  
Toru Nammoku ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Natriuretic Peptides ◽  
Mrna Levels ◽  
Catecholamine Synthesis ◽  
Th Mrna

scholarly journals MON-201 Effects of Incretins on Catecholamine Synthesis by Rat Pheochromocytoma PC12 Cells

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Motoshi Komatsubara ◽  
Satoshi Fujisawa ◽  
Takahiro Nada ◽  
Nahoko Iwata ◽  
Fumio Otsuka
Keyword(s):  
Pc12 Cells ◽  
Adrenal Medulla ◽  
Gastric Inhibitory Polypeptide ◽  
Dopamine Synthesis ◽  
Mrna Levels ◽  
Catecholamine Synthesis ◽  
Dipeptidyl Peptidase 4 ◽  
Pheochromocytoma Pc12 ◽  
Pheochromocytoma Pc12 Cells ◽  
Th Mrna

Abstract Incretins, such as gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are metabolic hormones secreted from the intestine to stimulate insulin secretion from the pancreatic β cells. Dipeptidyl peptidase-4 (DPP-4) inhibitors, as anti-diabetic agents, increase the bioavailability of both GIP and GLP-1. Since the receptor expressions of GIP and GLP-1 are detected in various organs, incretins have been suggested to affect many kinds of tissues and organs in addition to their insulinotropic effects. For instance, GIP and GLP-1 have been reported to regulate ovarian steroidogenesis and hypothalamic-pituitary-adrenal axis including secretions of adrenocorticotropin from the pituitary and cortisol from the adrenal cortex. However, the roles of GIP and GLP-1 in the adrenal medulla have not been recognized. Here we focused on the activity of bone morphogenetic protein (BMP)-4, which is expressed in the adrenal medulla and is functionally involved in the control of catecholamine synthesis. We earlier reported that BMP-4 treatment decreased catecholamine synthesis via smad1/5/9 phosphorylation and regulated catecholamine synthesis by cooperating with glucocorticoid and melatonin in rat pheochromocytoma PC12 cells. In the present study, roles of GIP and GLP-1 in the regulation of catecholamine production were studied using PC12 cells by focusing on interaction with BMP-4 and adrenocortical steroids. Both of GIP receptor and GLP-1 receptor expressions were detected in PC12 cells. Of note, treatments with GIP, but not with GLP-1, increased dopamine synthesis and the mRNA levels of catecholamine synthetic enzymes including tyrosine hydroxylase (TH), which is a rate-limiting enzyme for catecholamine synthesis, DOPA decarboxylase (DDC), and dopamine β-hydroxylase (DBH), by PC12 cells. Treatments with GIP enhanced glucocorticoid- and aldosterone-induced TH mRNA levels by upregulating the expressions of glucocorticoid receptor (GR) as well as mineralocorticoid receptor (MR). However, treatment with GLP-1 had no effect on corticosteroid-induced TH mRNA levels or GR/MR expression. On the other hand, treatment with GIP attenuated the inhibitory effect of BMP-4 that enables to decrease TH mRNA levels by suppressing BMP-induced Smad1/5/9 phosphorylation and Id-1 transcription. Furthermore, GIP treatment upregulated the expression of inhibitory Smad7, possibly leading to the suppression of BMP-4 signaling by PC12 cells. Collectively, it was revealed that incretins, in particular, GIP has an inducing effect on catecholamine synthesis through inhibiting BMP activities as well as enhancing corticosteroid actions in adrenomedullar cells.

scholarly journals Protective Effect of Psoralea corylifolia L. Seed Extract against Palmitate-Induced Neuronal Apoptosis in PC12 Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Yunkyoung Lee ◽  
Hee-Sook Jun ◽  
Yoon Sin Oh
Keyword(s):  
Pc12 Cells ◽  
Molecular Mechanisms ◽  
Neuronal Cell ◽  
Marker Genes ◽  
Heme Oxygenase 1 ◽  
Mrna Levels ◽  
Protective Effects ◽  
Psoralea Corylifolia ◽  
Antioxidant Genes ◽  
Bax Protein

The extract of Psoralea corylifolia seeds (PCE) has been widely used as a herbal medicine because of its beneficial effect on human health. In this study, we investigated the protective effects and molecular mechanisms of PCE on palmitate- (PA-) induced toxicity in PC12 cells, a neuron-like cell line. PCE significantly increased cell viability in PA-treated PC12 cells and showed antiapoptotic effects, as evidenced by decreased expression of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, and bax protein as well as increased expression of bcl-2 protein. In addition, PCE treatment reduced PA-induced reactive oxygen species production and upregulated mRNA levels of antioxidant genes such as nuclear factor (erythroid-derived 2)-like 2 and heme oxygenase 1. Moreover, PCE treatment recovered the expression of autophagy marker genes such as beclin-1 and p62, which was decreased by PA treatment. Treatment with isopsoralen, one of the major components of PCE extract, also recovered the expression of autophagy marker genes and reduced PA-induced apoptosis. In conclusion, PCE exerts protective effects against lipotoxicity via its antioxidant function, and this effect is mediated by activation of autophagy. PCE might be a potential pharmacological agent to protect against neuronal cell injury caused by oxidative stress or lipotoxicity.

scholarly journals Sesamin Modulates Tyrosine Hydroxylase, Superoxide Dismutase, Catalase, Inducible No Synthase and Interleukin-6 Expression in Dopaminergic Cells Under Mpp+-Induced Oxidative Stress

2008 ◽  
Vol 1 (1) ◽  
pp. 54-62 ◽  
Author(s):  
Vicky Lahaie-Collins ◽  
Julie Bournival ◽  
Marilyn Plouffe ◽  
Julie Carange ◽  
Maria-Grazia Martinoli
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Tyrosine Hydroxylase ◽  
Protein Expression ◽  
Pc12 Cells ◽  
Interleukin 6 ◽  
Estrogen Receptor Alpha ◽  
Strong Increase ◽  
Mrna Levels ◽  
Neuronal Pc12 Cells

Oxidative stress is regarded as a mediator of nerve cell death in several neurodegenerative disorders, such as Parkinson's disease. Sesamin, a lignan mainly found in sesame oil, is currently under study for its anti-oxidative and possible neuroprotective properties. We used 1-methyl-4-phenyl-pyridine (MPP+) ion, the active metabolite of the potent parkinsonism-causing toxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, to produce oxidative stress and neurodegeneration in neuronal PC12 cells, which express dopamine, as well as neurofilaments. Our results show that picomolar doses of sesamin protected neuronal PC12 cells from MPP+-induced cellular death, as revealed by colorimetric measurements and production of reactive oxygen species. We also demonstrated that sesamin acted by rescuing tyrosine hydroxylase levels from MPP+-induced depletion. Sesamin, however, did not modulate dopamine transporter levels, and estrogen receptor-alpha and -beta protein expression. By examining several parameters of cell distress, we found that sesamin also elicited a strong increase in superoxide dismutase activity as well as protein expression and decreased catalase activity and the MPP+stimulated inducible nitric oxide synthase protein expression, in neuronal PC12 cells. Finally, sesamin possessed significant anti-inflammatory properties, as disclosed by its potential to reduce MPP+-induced interleukin-6 mRNA levels in microglia. From these studies, we determined the importance of the lignan sesamin as a neuroprotective molecule and its possible role in complementary and/or preventive therapies of neurodegenerative diseases.

scholarly journals Effects of Insulin Treatment without and with Recurrent Hypoglycemia on Hypoglycemic Counterregulation and Adrenal Catecholamine-Synthesizing Enzymes in Diabetic Rats

Endocrinology ◽  
2006 ◽  
Vol 147 (4) ◽  
pp. 1860-1870 ◽  
Author(s):  
Karen E. Inouye ◽  
Jessica T. Y. Yue ◽  
Owen Chan ◽  
Tony Kim ◽  
Eitan M. Akirav ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Insulin Treatment ◽  
Diabetic Rats ◽  
Hyperinsulinemic Hypoglycemia ◽  
Mrna Levels ◽  
Relevant Model ◽  
Counterregulatory Hormones ◽  
Catecholamine Synthesizing Enzymes ◽  
Recurrent Hypoglycemia ◽  
Th Mrna

Untreated diabetic rats show impaired counterregulation against hypoglycemia. The blunted epinephrine responses are associated with reduced adrenomedullary tyrosine hydroxylase (TH) mRNA levels. Recurrent hypoglycemia further impairs epinephrine counterregulation and is also associated with reduced phenylethanolamine N-methyltransferase mRNA. This study investigated the adaptations underlying impaired counterregulation in insulin-treated diabetic rats, a more clinically relevant model. We studied the effects of insulin treatment on counterregulatory hormones and adrenal catecholamine-synthesizing enzymes and adaptations after recurrent hypoglycemia. Groups included: normal; diabetic, insulin-treated for 3 wk (DI); and insulin-treated diabetic exposed to seven episodes (over 4 d) of hyperinsulinemic-hypoglycemia (DI-hypo) or hyperinsulinemic-hyperglycemia (DI-hyper). DI-hyper rats differentiated the effects of hyperinsulinemia from those of hypoglycemia. On d 5, rats from all groups were assessed for adrenal catecholamine-synthesizing enzyme levels or underwent hypoglycemic clamps to examine counterregulatory responses. Despite insulin treatment, fasting corticosterone levels remained increased, and corticosterone responses to hypoglycemia were impaired in DI rats. However, glucagon, epinephrine, norepinephrine, and ACTH counterregulatory defects were prevented. Recurrent hypoglycemia in DI-hypo rats blunted corticosterone but, surprisingly, not epinephrine responses. Norepinephrine and ACTH responses also were not impaired, whereas glucagon counterregulation was reduced due to repeated hyperinsulinemia. Insulin treatment prevented decreases in basal TH protein and increased PNMT and dopamine β-hydroxylase protein. DI-hypo rats showed increases in TH, PNMT, and dopamine β-hydroxylase. We conclude that insulin treatment of diabetic rats protects against most counterregulatory defects but not elevated fasting corticosterone and decreased corticosterone counterregulation. Protection against epinephrine defects, both without and with antecedent hypoglycemia, is associated with enhancement of adrenal catecholamine-synthesizing enzyme levels.

Natriuretic peptides inhibit apoptosis and prolong the survival of serum-deprived PC12 cells

Neuroreport ◽  
2001 ◽  
Vol 12 (2) ◽  
pp. 185-189 ◽  
Author(s):  
Ronald R. Fiscus ◽  
Alex W. K. Tu ◽  
Siew Boon Cheng Chew
Keyword(s):  
Pc12 Cells ◽  
Natriuretic Peptides

scholarly journals Direct transcriptional stimulation of the ornithine decarboxylase gene by Fos in PC12 cells but not in fibroblasts.

1993 ◽  
Vol 13 (8) ◽  
pp. 4657-4669 ◽  
Author(s):  
C Wrighton ◽  
M Busslinger
Keyword(s):  
Transcription Factor ◽  
Pc12 Cells ◽  
Ornithine Decarboxylase ◽  
Transcription Initiation ◽  
Prolonged Exposure ◽  
Gene Activation ◽  
Neuronal Cell ◽  
Regulatory Sequences ◽  
Mrna Levels ◽  
Stimulation Of

We have established rat PC12 pheochromocytoma cell lines stably expressing the estrogen-activatable transcription factor FosER to identify genes that can be regulated by c-Fos in this neuronal cell type. Induction of ectopic c-Fos activity in PC12 cells increased the mRNA levels of the ornithine decarboxylase (ODC) and tyrosine hydroxylase genes with similar kinetics and to the same maximal level as nerve growth factor treatment. In both cases the rate of transcription initiation was increased. Induction of the ODC gene occurred even in the absence of protein synthesis, indicating direct regulation by FosER. ODC expression, however, was not induced by a mutant FosER protein containing a proline insertion in the basic region of the c-Fos moiety, demonstrating the requirement for a functional DNA-binding domain. These data show that FosER, and by extrapolation c-Fos, can directly activate transcription of the endogenous ODC gene in PC12 cells by binding to cis-regulatory sequences. Activation of the ODC gene was unexpectedly transient, as transcripts returned to the basal level after prolonged exposure of PC12 cells to FosER activity. Furthermore, ODC transcription was not at all induced by FosER in rat fibroblasts. To account for this cell-specific action of FosER, we propose that stimulation of the ODC gene by FosER requires either (i) cooperation with another transcription factor(s) or (ii) a specific pattern of modification which is present in PC12 cells but not in otherwise unstimulated fibroblasts. One or both of these mechanisms may be employed by cells to achieve selective gene activation in response to apparently stereotyped induction of c-fos.

Orexins Suppress Catecholamine Synthesis and Secretion in Cultured PC12 Cells

2000 ◽  
Vol 274 (2) ◽  
pp. 310-315 ◽  
Author(s):  
Toru Nanmoku ◽  
Kazumasa Isobe ◽  
Takeshi Sakurai ◽  
Akihiro Yamanaka ◽  
Kazuhiro Takekoshi ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Catecholamine Synthesis

Effects of the JNK inhibitor anthra[1,9-cd]pyrazol-6(2H)-one (SP-600125) on soluble guanylyl cyclase α1gene regulation and cGMP synthesis

2005 ◽  
Vol 289 (4) ◽  
pp. C778-C784 ◽  
Author(s):  
Joshua S. Krumenacker ◽  
Alexander Kots ◽  
Ferid Murad
Keyword(s):  
Pc12 Cells ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Fetal Lung ◽  
Cell Types ◽  
Mrna Levels ◽  
Disease States ◽  
Jun Kinase ◽  
Constitutively Active

The decreased expression of the nitric oxide (NO) receptor, soluble guanylyl cyclase (sGC), occurs in response to multiple stimuli in vivo and in cell culture and correlates with various disease states such as hypertension, inflammation, and neurodegenerative disorders. The ability to understand and modulate sGC expression and cGMP levels in any of these conditions could be a valuable therapeutic tool. We demonstrate herein that the c-Jun NH2-terminal kinase JNK II inhibitor anthra[1,9- cd]pyrazol-6(2 H)-one (SP-600125) completely blocked the decreased expression of sGCα1-subunit mRNA by nerve growth factor (NGF) in PC12 cells. Inhibitors of the ERK and p38 MAPK pathways, PD-98059 and SB-203580, had no effect. SP-600125 also inhibited the NGF-mediated decrease in the expression of sGCα1protein as well as sGC activity in PC12 cells. Other experiments revealed that decreased sGCα1mRNA expression through a cAMP-mediated pathway, using forskolin, was not blocked by SP-600125. We also demonstrate that TNF-α/IL-1β stimulation of rat fetal lung (RFL-6) fibroblast cells resulted in sGCα1mRNA inhibition, which was blocked by SP-600125. Expression of a constitutively active JNKK2-JNK1 fusion protein in RFL-6 cells caused endogenous sGCα1mRNA levels to decrease, while a constitutively active ERK2 protein had no effect. Collectively, these data demonstrate that SP-600125 may influence the intracellular levels of the sGCα1-subunit in certain cell types and may implicate a role for c-Jun kinase in the regulation of sGCα1expression.

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