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At least 109 records · Page 6Linked to original sources
PubMed2005

Low concentrations of nitric oxide (NO) induced cell death in PC12 cells through activation of p38 mitogen-activated protein kinase (p38 MAPK) but not via extracellular signal-regulated kinases (ERK1/2) or c-Jun N-terminal protein kinase (JNK).

Nitric oxide (NO), a highly reactive gaseous molecule, has been previously reported to induce apoptosis-like cell death even at a low concentration in PC12 cells. In this study, we examined NO-induced activation of members of the mitogen-activated protein kinase (MAPK) family, i.e., p38 MAPK, extracellular signal-regulated kinases (ERK1/2), and c-Jun N-terminal protein kinase (JNK). Following the exposure of PC12 cells to an NO donor, (+)-(E)-4-ethyl-2-[hydroxyimino]-5-nitro-3-hexenamide (NOR3; 100 muM), the phosphorylation level of p38 MAPK increased time dependently from 2 to 6 h, but that of both ERK1/2 and JNK did not. Treatment with a p38 MAPK inhibitor SB203580 partially blocked the NOR3-induced cell death. Neither PD98059, U0126 (inhibitors of ERK1/2) nor SP600125 (a specific inhibitor of JNK) treatments had any significant effect on the NOR3-induced cell death. These findings suggest that the activation of a p38 MAPK pathway, but not that of ERK1/2 or JNK, plays an essential role in the apoptosis-like cell death induced by low concentrations of NO.

Analysis of Variance↗
PubMed1990

Regulation of sodium currents and acetylcholine responses in PC12 cells.

Voltage-gated sodium currents and acetylcholine-elicited currents in clonal rat pheochromocytoma cells (PC12) were studied using the whole-cell patch-clamp technique. After treatment of cultures with nerve growth factor (NGF, 2-4 nM) for 5 or more days, both Na currents and ACh responses increased by 5-7-fold. We tested the ability of a number of treatments reported to induce physiological differentiation in neuroblastoma or neuroblastoma-glioma hybrid cells. We found that no treatment was as effective as NGF, and mitotic inhibitors and 8-bromocyclic AMP reduced the efficacy of NGF at increasing both sodium currents and ACh responses. Some treatments were able to selectively reduce or enhance the ability of NGF to induce ACh responses or sodium currents. Dexamethasone, in particular, completely blocked the NGF-induced increase in ACh response, while leaving Na currents unaffected. Furthermore, in individual cells the Na current density and ACh current density are uncorrelated. These observations indicate that physiological differentiation in PC12 cells is regulated differently than in neuroblastoma cells and, further, in PC12 cells sodium currents and ACh responses are independently regulated.

Acetylcholine↗
PubMed1990

Hydrolysis-resistant GTP analogs stimulate catecholamine release from digitonin-permeabilized PC12 cells.

The effect of the hydrolysis-resistant GTP analogs, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and guanylyl imidodiphosphate (GMPPNP), on norepinephrine (NE) secretion from digitonin-permeabilized rat pheochromocytoma cells, PC12, was examined. Although secretion in the presence of saturating Ca2+ (10 microM) was not affected by GTP gamma S or GMPPNP, secretion in the absence of Ca2+ was stimulated by these GTP analogs. Secretion induced by saturating concentrations of GTP gamma S or GMPPNP was approximately 80% of that induced by 10 microM Ca2+. Half-maximum stimulation was induced by 30 microM GTP gamma S or GMPPNP. Both Ca2(+)-stimulated and GTP gamma S-stimulated secretion were ATP dependent and inhibited by N-ethylmaleimide. The GTP gamma S-stimulated secretion of NE from permeabilized PC12 cells does not appear to result from either the release of Ca2+ or the activation of protein kinase C. Activation of protein kinase C by pretreatment of intact cells with 12-O-tetradecanoylphorbol 13-acetate caused a 50% increase in both Ca2(+)-stimulated and GTP gamma S-stimulated secretion. Cholera and pertussis toxins did not affect Ca2(+)-stimulated or GTP gamma S-stimulated NE secretion. Guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) and GTP inhibited GTP gamma S-stimulated secretion but not Ca2(+)-stimulated secretion. The inability of GDP beta S to inhibit Ca2(+)-stimulated secretion indicates that the process affected by GTP gamma S is not an essential step in the Ca2(+)-stimulated pathway.

Adenosine Triphosphate↗
PubMed1990

Reconstituted basement membrane enhances neurite outgrowth in PC12 cells induced by nerve growth factor.

Rat pheochromocytoma cells (PC12) respond to nerve growth factor (NGF) by elaborating neurites. We have studied the effect of extracellular matrix proteins on responsiveness of PC12 cells to NGF. NGF elicited neurite outgrowth in cells plated on collagen, fibronectin, or laminin within 48-72 h. In contrast, cells entrapped in reconstituted basement membrane prepared from the Engelbreth-Holm-Swarm tumor (EHS-BM) responded within 24 h. Cells plated on collagen or fibronectin required a minimal dose of 50 ng/ml NGF to achieve the same effect as cells entrapped in EHS-BM at 1 ng/ml NGF. Neurites displayed by cells plated in EHS-BM were more extensively branched and remained intact up to 21 days following a single administration of NGF.

Adrenal Gland Neoplasms↗
PubMed2006

Piperine inhibition of 1-methyl-4-phenylpyridinium-induced mitochondrial dysfunction and cell death in PC12 cells.

The effect of alkaloid piperine against the toxicity of 1-methyl-4-phenylpyridinium (MPP(+)) in differentiated PC12 cells was assessed. Piperine treatment revealed a differential effect on the cytotoxicity of MPP(+) and had its maximum inhibitory effect at 1 microM. The addition of piperine (0.5-10 microM) significantly reduced the MPP(+)-induced nuclear damage, mitochondrial membrane permeability changes, formation of reactive oxygen species and depletion of GSH. In contrast, piperine at 50-100 microM showed cytotoxicity and exhibited an additive effect against the MPP(+) toxicity. The results indicate that piperine had a differential effect on the cytotoxicity of MPP(+) depending on concentration. Piperine at low concentrations may reduce the MPP(+)-induced viability loss in PC12 cells by suppressing the changes in the mitochondrial membrane permeability, leading to the release of cytochrome c and subsequent activation of caspase-3. The effects may be ascribed to its inhibitory action on the formation of reactive oxygen species and depletion of GSH.

1-Methyl-4-phenylpyridinium↗
PubMed2003

Oxygen sensing in neuroendocrine cells and other cell types: pheochromocytoma (PC12) cells as an experimental model.

A steady supply of oxygen is an absolute requirement for mammalian cells to maintain normal cellular functions. To answer the challenge that oxygen deprivation represents, mammals have evolved specialized cell types that can sense changes in oxygen tension and alter gene expression to enhance oxygen delivery to hypoxic areas. These oxygensensing cells are rare and difficult to study in vivo. As a result, pheochromocytoma (PC12) cells have become a vital in vitro model system for deciphering the molecular events that confer the hypoxia-resistant and oxygen-sensing phenotypes. Research over the last few years has revealed that the hypoxia response in PC12 cells involves the interactions of several signal transduction pathways (Ca2+/calmodulin-dependent kinases, Akt, SAPKs, and MAPKs) and transcription factors (HIFs, CREB, and c-fos/junB). This review summarizes the current understanding of the role these signal transduction pathways and transcription factors play in determining the hypoxic response.

Animals↗
PubMed2005

Acrolein-induced cell death in PC12 cells: role of mitochondria-mediated oxidative stress.

Oxidative stress has been implicated in acrolein cytotoxicity in various cell types, including mammalian spinal cord tissue. In this study we report that acrolein also decreases PC12 cell viability in a reactive oxygen species (ROS)-dependent manner. Specifically, acrolein-induced cell death, mainly necrosis, is accompanied by the accumulation of cellular ROS. Elevating ROS scavengers can alleviate acrolein-induced cell death. Furthermore, we show that exposure to acrolein leads to mitochondrial dysfunction, denoted by the loss of mitochondrial transmembrane potential, reduction of cellular oxygen consumption, and decrease of ATP level. This raises the possibility that the cellular accumulation of ROS could result from the increased production of ROS in the mitochondria of PC12 cells as a result of exposure to acrolein. The acrolein-induced significant decrease of ATP production in mitochondria may also explain why necrosis, not apoptosis, is the dominant type of cell death. In conclusion, our data suggest that one possible mechanism of acrolein-induced cell death could be through mitochondria as its initial target. The subsequent increase of ROS then inflicts cell death and further worsens mitochondria function. Such mechanism may play an important role in CNS trauma and neurodegenerative diseases.

Acrolein↗
PubMed2006

7-Ketocholesterol enhances 1-methyl-4-phenylpyridinium-induced mitochondrial dysfunction and cell death in PC12 cells.

The present study investigated the promoting effect of oxysterol 7-ketocholesterol against the cytotoxicity of 1-methyl-4-phenylpyridinium (MPP(+)) in differentiated PC12 cells. 7-Ketocholesterol significantly enhanced the MPP(+)-induced nuclear damage, decrease in the mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the formation of reactive oxygen species and depletion of GSH. N-Acetylcysteine, ascorbate, trolox, carboxy-PTIO and Mn-TBAP reduced the cytotoxic effect of MPP(+) in the presence of 7-ketocholesterol. The results indicate that 7-ketocholesterol shows a synergistic effect against the cytotoxic effect of MPP(+). 7-Ketocholesterol may enhance the MPP(+)-induced viability loss in PC12 cells by promoting the mitochondrial membrane permeability change, release of cytochrome c and subsequent activation of caspase-3, which is associated with the increased formation of reactive oxygen species and depletion of GSH. The findings suggest that 7-ketocholesterol as a promoting agent for the formation of mitochondrial permeability transition may enhance the toxic neuronal cell injury.

Animals↗
PubMed2001

Effects of methylmercury and mercuric chloride on differentiation and cell viability in PC12 cells.

The effects of methylmercury (CH3Hg) or mercuric chloride (HgCl(2)) on neurite outgrowth and cell viability were quantified using undifferentiated (unprimed) and differentiated (primed) pheochromocytoma (PC12) cells. In unprimed cells, following 24-h exposure, CH3Hg significantly decreased NGF-stimulated neurite outgrowth at concentrations of 0.3-3 microM. However, HgCl(2) significantly increased both neurite outgrowth and the number of branch points, a component of neurite outgrowth. In primed PC12 cells, following 24-h exposure, both CH3Hg and HgCl(2) inhibited NGF-stimulated neurite outgrowth with an EC(50) of approximately 0.03 microM; however, there was a difference between CH3Hg and HgCl(2) effects on the subcomponents of total neurite outgrowth. CH3Hg significantly decreased both the number of branch points (0.3 microM) and fragment length (0.01 microM), while HgCl(2) only decreased fragment length (0.03 microM). Cell viability was assessed in the same cultures by trypan-blue exclusion. In unprimed cells, the EC(50) for cytotoxicity of CH3Hg in the presence and absence of NGF was 0.21 +/- 0.04 and 0.87 +/- 0.12 microM, respectively, and for HgCl(2) in the presence and absence of NGF was 8.18 +/- 1.52 and 5.02 +/- 0.74 microM, respectively. In primed cells, the EC(50) for cytotoxicity of CH3Hg in the presence or absence of NGF was 1.17 +/- 0.38 and 0.73 +/- 0.14 microM, respectively, and for HgCl(2) in the presence or absence of NGF was 3.96 +/- 0.82 and 3.81 +/- 0.91 microM, respectively. In the primed PC12 model, cytotoxicity occurred at concentrations that were at least 30-fold higher than the EC(50) for neurite outgrowth, suggesting that the mercurial compounds can act selectively on the process of differentiation.

Animals↗
PubMed2002

Antiapoptotic and cytotoxic properties of delta opioid peptide [D-Ala(2),D-Leu(5)]enkephalin in PC12 cells.

The delta opioid peptide [D-Ala(2),D-Leu(5)]enkephalin (DADLE) has been shown to promote organ survival and to protect against methamphetamine-induced neurodegeneration. However, the cellular mechanisms of these actions of DADLE are not totally clear. We examined the action of DADLE in serum-deprived pheochromocytoma cells (PC12) and found that DADLE protected against cell death in those cells. However, the dose-response curves of the protective effects of DADLE are U-shaped as judged by three biochemical or morphological assays: the LDH release, the DNA laddering, and the apoptotic nuclei. It was found that femtomolar to picomolar concentrations of DADLE are antiapoptotic, whereas micormolar concentrations of DADLE are cytotoxic in PC12 cells. The protective effect of DADLE could be attenuated by a selective delta2 opioid antagonist and the cytotoxic action of DADLE was reduced by a selective mu opioid receptor antagonist. The treatment of cells with PD98059, a selective inhibitor of ERK kinase (MEK), or the transfection of cells with a dominant interfering form of MEK (MEK-KA97) blocked both the protective effect of DADLE and the ERK phosphorylation induced by DADLE. Cytotoxic concentrations of DADLE, on the other hand, caused an increase of Fas-ligand (FasL) in PC12 cells that was attenuated by a selective mu antagonist. Our results suggest, therefore, that endogenous opioid peptides may, at low concentrations, promote cell survival via the MEK-ERK pathway perhaps through delta2 opioid receptors, whereas they may kill cells at high concentrations via the activation of FasL through an as-yet unknown mechanism involving mu opioid receptors.

Animals↗
PubMed2006

Neuroprotective effect of carnosine on necrotic cell death in PC12 cells.

The nervous tissue of many vertebrates, including humans, can synthesize beta-alanyl-L-histidine (carnosine). The biological functions of carnosine are still open to question, although several theories supported by strong experimental data have been proposed. The objective of this study was to examine the effects of carnosine on neurotoxicity in differentiated rat pheochromocytoma (PC12) cells. Neurotoxicity was induced by N-methyl-D-aspartate (NMDA), which caused time- and concentration-dependent cell death as measured by MTT and LDH assays. Pretreatment with carnosine significantly prevented the neurotoxicity in a concentration-dependent manner. The protective effect of carnosine was antagonized by the H1 receptor antagonist pyrilamine, but not by the H2 receptor antagonist cimetidine. In addition, alpha-fluoromethylhistidine, a histidine decarboxylase inhibitor, slightly reversed the protective action of carnosine. These results indicate that carnosine can effectively protect against NMDA-induced necrosis in PC12 cells, and its protection may in part be due to the activation of the postsynaptic histamine H1 receptor. The study suggests that carnosine may be an endogenous protective factor and calls for its further study as a new anti-excitotoxic agent.

Animals↗
PubMed2003

Involvement of Gas7 in nerve growth factor-independent and dependent cell processes in PC12 cells.

Gas7, a growth arrest-specific gene originally isolated from serum-starved mouse fibroblast cells, is expressed in vivo predominantly in the brain and is required for neurite formation in cultured mouse cerebellar neurons (Ju et al. [1998] Proc. Natl. Acad. Sci. USA 95: 11423-11428). Here we report that Gas7 plays a key role in the morphological differentiation of PC12 preneuronal rat pheochromocytoma cells (PC12 cells). We found that overexpression of murine Gas7 in PC12 cells leads to an expanded cell morphology and promotes spike-like cell processes that resemble the early stages of neurite formation. These processes undergo elongation upon addition of nerve growth factor (NGF). We also found that the addition of NGF induces the production of endogenous rat-Gas7 (rGas7), which is transiently elevated prior to the appearance of NGF-promoted neurite outgrowths. Furthermore, inhibition of endogenous rGas7 production by antisense nucleotides complimentary to the translation initiation region of a rGas7 cDNA (AJ131902) reduces the NGF-promoted neurite outgrowths. Our results demonstrate that Gas7 by itself influences early cell morphological development and likely functions as an early-stage intermediary in NGF-induced neuronal differentiation of PC12 culture cells.

Animals↗
PubMed2004

Methylmercury inhibits TrkA signaling through the ERK1/2 cascade after NGF stimulation of PC12 cells.

Using PC12 cells as a model of neuronal differentiation, we have shown that acute exposure to methylmercury (CH3Hg) inhibits nerve growth factor (NGF)-induced activation of TrkA. In the present study, we examined the effects of CH3Hg on pathways activated by NGF. NGF-induced phosphorylation of ERK1/2 in PC12 cells was time-dependent. Concurrent exposure to CH3Hg and NGF for 2.5 min resulted in a concentration-dependent inhibition of ERK1/2 phosphorylation (EC50 = 0.018 microM). However, NGF-stimulated ERK1/2 phosphorylation was not altered after 5 min of exposure to CH3Hg. In vitro studies revealed that CH3Hg did not directly inhibit the ERK kinase MEK. As reported in other neuronal tissue, CH3Hg can inhibit PKC activity in vitro. Incubation of PC12 cell lysates with CH3Hg produced a concentration-dependent inhibition of PKC activity that was significant at 0.3-10 microM. Further studies using recombinant enzymes examined the effect of CH3Hg on PKC isoforms expressed in PC12 cells. CH3Hg inhibited PKCdelta, and zeta activity in a concentration-dependent manner at higher concentrations (3-10 microM), while a significant increase in PKCalpha activity was observed at lower concentrations (0.1 microM). However, CH3Hg had no affect on NGF-induced PKC activity in intact cells. These results show that CH3Hg inhibition of NGF-stimulated TrkA activation in PC12 cells decreases downstream signaling through the Raf/MEK/ERK cascade. In intact cells PKC does not appear to be a primary target for CH3Hg.

Animals↗
PubMed1992

Nerve growth factor withdrawal-induced cell death in neuronal PC12 cells resembles that in sympathetic neurons.

Previous studies have shown that in neuronal cells the developmental phenomenon of programmed cell death is an active process, requiring synthesis of both RNA and protein. This presumably reflects a requirement for novel gene products to effect cell death. It is shown here that the death of nerve growth factor-deprived neuronal PC12 cells occurs at the same rate as that of rat sympathetic neurons and, like rat sympathetic neurons, involves new transcription and translation. In nerve growth factor-deprived neuronal PC12 cells, a decline in metabolic activity, assessed by uptake of [3H]2-deoxyglucose, precedes the decline in cell number, assessed by counts of trypan blue-excluding cells. Both declines are prevented by actinomycin D and anisomycin. In contrast, the death of nonneuronal (chromaffin-like) PC12 cells is not inhibited by transcription or translation inhibitors and thus does not require new protein synthesis. DNA fragmentation by internucleosomal cleavage does not appear to be a consistent or significant aspect of cell death in sympathetic neurons, neuronal PC12 cells, or nonneuronal PC12 cells, notwithstanding that the putative nuclease inhibitor aurintricarboxylic acid protects sympathetic neurons, as well as neuronal and nonneuronal PC12 cells, from death induced by trophic factor removal. Both phenotypic classes of PC12 cells respond to aurintricarboxylic acid with similar dose-response characteristics. Our results indicate that programmed cell death in neuronal PC12 cells, but not in nonneuronal PC12 cells, resembles programmed cell death in sympathetic neurons in significant mechanistic aspects: time course, role of new protein synthesis, and lack of a significant degree of DNA fragmentation.

Animals↗
PubMed1998

ATP-stimulated activation of the mitogen-activated protein kinases through ionotrophic P2X2 purinoreceptors in PC12 cells. Difference in purinoreceptor sensitivity in two PC12 cell lines.

Extracellular purine nucleotides elicit a diverse range of biological responses through binding to specific cell surface receptors. The ionotrophic P2X subclass of purinoreceptors respond to ATP by stimulation of calcium ion permeability; however, it is unknown how P2X purinoreceptor activation is linked to intracellular signaling pathways. We report that stimulation of PC12 cells with ATP results in the activation of the mitogen-activated protein (MAP) kinases ERK1 and ERK2 and was wholly dependent upon extracellular calcium ions. Treatment of the cells with adenosine, AMP, ADP, UTP, or alpha,beta-methylene ATP was without effect; however, MAP kinase activation was abolished by pretreatment with suramin and reactive blue 2. The calcium-activated tyrosine kinase, Pyk2, acts as an upstream regulator of the MAP kinases and became tyrosine phosphorylated following treatment of the cells with ATP. We have ruled out the involvement of depolarization-mediated calcium influx because specific blockers of voltage-gated calcium channels did not affect MAP kinase activation. These data provide direct evidence that calcium influx through P2X2 receptors results in the activation of the MAP kinase cascade. Finally, we demonstrate that a different line of PC12 cells respond to ATP through P2Y2 purinoreceptors, providing an explanation for the conflicting findings of purine nucleotide responsiveness in PC12 cells.

Adenosine Triphosphate↗
PubMed1997

Differential effects of thiopental on neuronal nicotinic acetylcholine receptors and P2X purinergic receptors in PC12 cells.

BACKGROUND: PC12 cells, derived from rat pheochromocytoma, express neuronal nicotinic acetylcholine receptors (nAchRs) and P2X purinergic receptors, both of which resemble the receptors in postganglionic sympathetic neurons. The former is the established and the latter is the putative receptor to mediate fast synaptic transmission. The authors investigated effects of thiopental on these two ligand-gated ion channels. METHODS: Whole cell currents were recorded in PC12 cells without treatment of nerve growth factor, using conventional whole cell patch clamp technique. Nicotine or adenosine triphosphate (ATP) 30 microM was applied for 4-5 s in the absence or presence of thiopental 3-300 microM. RESULTS: Nicotine induced the rapidly decaying inward current at -60 mV, which exhibited the characteristics of the neuronal nAchR-mediated current. Thiopental inhibited the nicotine-induced inward current and accelerated the current decay in a dose-dependent manner, resulting in the greater effects on the steady current than the peak current. IC50s for the peak and steady current were 56.7 and 7.4 microM, when the anesthetic was coapplied with nicotine. Thiopental's inhibition was not associated with a change in the reversal potential and was voltage-independent at membrane potential of -30 to -70 mV. Most of thiopental's effects seemed to require channel opening. In contrast to the nicotine-induced current, thiopental had little effect on the current elicited by ATP. CONCLUSIONS: Thiopental, whose reported EC50 for general anesthesia is 25 microM, inhibited the neuronal nAchR-mediated current but not the P2X receptor-mediated response in PC12 cells at clinically relevant concentrations. Inhibition may result in suppression of synaptic transmission in sympathetic ganglia.

Adenosine Triphosphate↗
PubMed1995

Nerve growth factor stimulates tyrosine phosphorylation and activation of Src homology-containing protein-tyrosine phosphatase 1 in PC12 cells.

Rat PC12 cells respond to extracellular peptide growth factors in at least two distinct ways. When treated with nerve growth factor (NGF) PC12 cells exit the cell cycle and differentiate to a neuronal phenotype, whereas when treated with epidermal growth factor, they proliferate. We examined the potential role of Src homology 2 (SH2)-containing protein tyrosine phosphatases (PTPs) in the differentiation process. PC12 cells express substantial amounts of both SH-PTP1 and 2. SH-PTP1, but not SH-PTP2, becomes tyrosine phosphorylated following NGF, but not epidermal growth factor treatment. The enzymatic activity of SH-PTP1 toward an exogenous substrate following NGF treatment is increased 2-fold. We found that SH-PTP1 binds to the NGF receptor TrkA in vitro and that anti-TrkA immunoprecipitates have PTP activity. These results show that SH-PTP1 is differentially phosphorylated and activated by NGF in PC12 cells and suggest that this activation may play a role in NGF-induced differentiation.

Animals↗
PubMed1993

Induction of peptidylglycine alpha-hydroxylating monooxygenase activity by nerve growth factor in PC12 cells.

Pheochromocytoma PC12 cells grown in the presence of nerve growth factor (NGF) undergo marked neuronal differentiation. During this process gene expression is altered, resulting in the activation of genes specific for neuronal properties, including the gene encoding neuropeptide Y (NPY). Here we sought to determine whether NGF also induces the activity of peptidylglycine alpha-hydroxylating monooxygenase (PHM) (EC1.4.17.3). PHM catalyzes the rate limiting step in the formation of alpha-amidated NPY from its glycine extended precursor, a posttranslational modification essential for biologic activity. PC12 cells were grown with or without NGF and assayed for PHM activity under optimal conditions. Whole cell extracts, medium and soluble and membrane bound fractions were assayed; total cellular PHM activity was found to be primarily membrane bound (fivefold greater than in soluble) and very little activity was released into the medium. Compared to control cells, PHM activity was increased significantly by NGF by 24 h but not before 4 h exposure. Through kinetic analysis, it was determined that the NGF-induction of PHM was a result of an increase in Vmax with no change in Km. It was found that the glucocorticoid, dexamethasone (DEX), decreased basal PHM activity and prevented its induction by NGF. Cotreatment with DEX for up to 7 d, however, did not dramatically alter the pronounced changes in cell morphology that occurred in response to NGF. These findings indicate that NGF and glucocorticoids exert reciprocal control over the activity of PHM in PC12 cells. As such, the process of differentiation in PC12 cells is a model for studying the mechanisms that coordinate the expression and activity of peptide processing enzymes with the regulation of their substrates and products.

Amino Acid Sequence↗