Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0031511 (pheochromocytoma)
 14,622 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of MEN type IIa is described showing among other symptoms, three attacks of transient neurological symptoms. These were attributed to a localized, transient cerebral ischemia. The latter probably developed as a consequence of the concomitant occurrence of different phenomena: the existence of hypercalcemia and on the other hand the secretion of vasoactive substances by one of the three tumours forming the MEN type IIa syndrome. The pheochromocytoma played an essential role because the symptoms did not recur after the bilateral adrenalectomy.
 ...
PMID:An unusual cause of attacks of focal cerebral symptoms: multiple endocrine neoplasia type IIA. 613 63

Oxidative stress is implicated in neuronal apoptosis that occurs in physiological settings and in neurodegenerative disorders. Superoxide anion radical, produced during mitochondrial respiration, is involved in the generation of several potentially damaging reactive oxygen species including peroxynitrite. To examine directly the role of superoxide and peroxynitrite in neuronal apoptosis, we generated neural cell lines and transgenic mice that overexpress human mitochondrial manganese superoxide dismutase (MnSOD). In cultured pheochromocytoma PC6 cells, overexpression of mitochondria-localized MnSOD prevented apoptosis induced by Fe2+, amyloid beta-peptide (Abeta), and nitric oxide-generating agents. Accumulations of peroxynitrite, nitrated proteins, and the membrane lipid peroxidation product 4-hydroxynonenal (HNE) after exposure to the apoptotic insults were markedly attenuated in cells expressing MnSOD. Glutathione peroxidase activity levels were increased in cells overexpressing MnSOD, suggesting a compensatory response to increased H2O2 levels. The peroxynitrite scavenger uric acid and the antioxidants propyl gallate and glutathione prevented apoptosis induced by each apoptotic insult, suggesting central roles for peroxynitrite and membrane lipid peroxidation in oxidative stress-induced apoptosis. Apoptotic insults decreased mitochondrial transmembrane potential and energy charge in control cells but not in cells overexpressing MnSOD, and cyclosporin A and caspase inhibitors protected cells against apoptosis, demonstrating roles for mitochondrial alterations and caspase activation in the apoptotic process. Membrane lipid peroxidation, protein nitration, and neuronal death after focal cerebral ischemia were significantly reduced in transgenic mice overexpressing human MnSOD. The data suggest that mitochondrial superoxide accumulation and consequent peroxynitrite production and mitochondrial dysfunction play pivotal roles in neuronal apoptosis induced by diverse insults in cell culture and in vivo.
 ...
PMID:Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduces ischemic brain injury: suppression of peroxynitrite production, lipid peroxidation, and mitochondrial dysfunction. 942 11

We have previously provided evidence that two transition metal cations, Zn2+ and Cu2+, can alter the conformation of nerve growth factor (NGF), rendering it unable to bind to its receptors or to activate signal transduction pathways. In the present study, we have assessed the influence of Zn2+ and Cu2+ on NGF-mediated protection from an oxidative insult. Exposure of rat pheochromocytoma (PC12) cells to hydrogen peroxide resulted in an increase in cell death via apoptosis, which was inhibited by NGF. Zn2+ and Cu2+, when added to cultures at a concentration of 100 microM, prevented NGF-mediated survival-promoting effects. Neither of these ions had an effect on basal cell viability (in the absence of NGF) after an oxidative insult. These results demonstrate that Zn2+ and Cu2+ can selectively inhibit NGF-mediated resistance to an oxidative stress, and have significant implications for neuronal function under both physiological and pathological (e.g. cerebral ischemia) conditions.
 ...
PMID:Zinc and copper inhibit nerve growth factor-mediated protection from oxidative stress-induced apoptosis. 1002 71

Cerebral ischemia and symptoms of stroke can occur as a rare manifestation in patients with pheochromocytoma. We describe a 45-year-old woman who was admitted because of a right-sided hemiparesis due to an ischemic lesion in the left hypothalamus. The clinical diagnosis of a pheochromocytoma was proven by highly elevated urinary catecholamines and confirmed histologically after operation. The successful removal of the tumor led to the almost complete recovery of the neurological deficiencies. It is of vital importance to know this atypical presentation of pheochromocytoma. The diagnosis of pheochromocytoma should be suspected in patients with focal cerebral symptoms, particularly in the presence of intermittent hypertension or other paroxysmal symptoms suggestive of pheochromocytoma.
 ...
PMID:Reversible cerebral ischemia in patients with pheochromocytoma. 1021 90

Prolonged exposure to hypoxia (10% O(2)) enhanced quantal catecholamine release evoked from O(2)-sensing pheochromocytoma (PC12) cells, as monitored using single-cell amperometric recordings. The enhancement of exocytosis was apparent after 12 h of hypoxia and was maximal at 24 h. Elevated levels of secretion were due to the emergence of a Ca(2+) influx pathway that persisted during complete blockade of known voltage-gated Ca(2+) channels. Secretion triggered by this Ca(2+) influx was severely reduced by known inhibitors of Alzheimer's amyloid beta-peptides (AbetaPs), including an N terminus-directed monoclonal antibody. The enhancing effect on secretion of chronic hypoxia was mimicked closely by direct application of AbetaP to cells under normoxic conditions, although the effects of AbetaP were more rapid at onset, being maximal after only 6 h. The present results suggest that prolonged hypoxia can induce formation of Ca(2+)-permeable AbetaP channels and that such induction can lead directly to excessive neurosecretion. This is a potential contributory factor to AbetaP pathophysiology following cerebral ischemia.
 ...
PMID:Hypoxic enhancement of quantal catecholamine secretion. Evidence for the involvement of amyloid beta-peptides. 1053 16

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates the adaptive response to hypoxia in mammalian cells. It consists of a regulatory subunit HIF-1alpha, which accumulates under hypoxic conditions, and a constitutively expressed subunit HIF-1beta. In this study we analyzed HIF-1alpha expression in the rat cerebral cortex after transient global ischemia induced by cardiac arrest and resuscitation. Our results showed that HIF-1alpha accumulates as early as 1 hr of recovery and persists for at least 7 d. In addition, the expression of HIF-1 target genes, erythropoietin and Glut-1, were induced at 12 hr to 7d of recovery. A logical explanation for HIF-1alpha accumulation might be that the brain remained hypoxic for prolonged periods after resuscitation. By using the hypoxic marker 2-(2-nitroimidazole-1[H]-y1)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5), we showed that the brain is hypoxic during the first hours of recovery from cardiac arrest, but the tissue is no longer hypoxic at 2 d. Thus, the initial ischemic episode must have activated other nonhypoxic mechanisms that maintain prolonged HIF-1alpha accumulation. One such mechanism might be initiated by insulin-like growth factor-1 (IGF-1). Our results showed that IGF-1 expression was upregulated after cardiac arrest and resuscitation. In addition, we showed that IGF-1 was able to induce HIF-1alpha in pheochromocytoma cells and cultured neurons as well as in the brain of rats that received intracerebroventricular and systemic IGF-1 infusion. Moreover, infusion of a selective IGF-1 receptor antagonist abrogates HIF-1alpha accumulation after cardiac arrest and resuscitation. Our study suggest that activation of HIF-1 might be part of the mechanism by which IGF-1 promotes cell survival after cerebral ischemia.
 ...
PMID:Activation of hypoxia-inducible factor-1 in the rat cerebral cortex after transient global ischemia: potential role of insulin-like growth factor-1. 1238 99

Alterations in lipid metabolism play an integral role in neuronal death in cerebral ischemia. Here we used an in vitro model, oxygen-glucose deprivation (OGD) of rat pheochromocytoma (PC12) cells, and analyzed changes in phosphatidylcholine (PC) and sphingomyelin (SM) metabolism. OGD (4-8 h) of PC12 cells triggered a dramatic reduction in PC and SM levels, and a significant increase in ceramide. OGD also caused increases in phosphatidylcholine-phospholipase C (PC-PLC) and phospholipase D (PLD) activities and PLD2 protein expression, and reduction in cytidine triphosphate:phosphocholine cytidylyltransferase-alpha (CCTalpha, the rate-limiting enzyme in PC synthesis) protein expression and activity. Phospholipase A2 activity and expression were unaltered during OGD. Increased neutral sphingomyelinase activity during OGD could account for SM loss and increased ceramide. Surprisingly, treatment with PC-PLC inhibitor tricyclodecan-9-yl potassium xanthate (D609) aggravated cell death in PC12 cells during OGD. D609 was cytotoxic only during OGD; cell death could be prevented by inclusion of sera, glucose or oxygen. During OGD, D609 caused further loss of PC and SM, depletion of 1,2-diacylglycerol (DAG), increase in ceramide and free fatty acids (FFA), cytochrome c release from mitochondria, increases in intracellular Ca2+ ([Ca2+]i), poly-ADP ribose polymerase (PARP) cleavage and phosphatidylserine externalization, indicative of apoptotic cell death. Exogenous PC during OGD in PC12 cells with D609 attenuated PC, SM loss, restored DAG, attenuated ceramide levels, decreased cytochrome c release, PARP cleavage, annexin V binding, attenuated the increase in [Ca2+]i, FFA release, and significantly increased cell viability. Exogenous PC may have elicited these effects by restoring membrane PC levels. A tentative scheme depicting the mechanism of action of D609 (inhibiting PC-PLC, SM synthase, PC synthesis at the CDP-choline-1,2-diacylglycerol phosphocholine transferase (CPT) step and causing mitochondrial dysfunction) has been proposed based on our observations and literature.
 ...
PMID:Effect of tricyclodecan-9-yl potassium xanthate (D609) on phospholipid metabolism and cell death during oxygen-glucose deprivation in PC12 cells. 1743 80

The commonly used inhaled anesthetic isoflurane has been shown to be both neuroprotective and neurotoxic in various cell cultures and animal models. We hypothesize that, like cerebral ischemia, isoflurane is inherently neurotoxic. Limited exposure of isoflurane provides neuroprotection via induction of endogenous neuroprotective mechanisms (preconditioning), while prolonged exposure of isoflurane induces neurotoxicity directly by its inherent neurotoxic effects. To test this hypothesis, we treated rat primary cortical neurons at different days in vitro (DIV) and rat pheochromocytoma neurosecretory (PC12) cells with or without Alzheimer's mutated presenilin-1 (PS1) with 2.4% isoflurane for 24 h to induce cell damage determined by both MTT (3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) reduction and LDH (lactate dehydrogenase) release assays. For isoflurane preconditioning, we treated the above cells with isoflurane at 0.6%, 1.2% and 2.4% for 60 min, 4 h prior to a prolonged exposure of 2.4% isoflurane for 24 h. One hour of preconditioning with isoflurane dose-dependently inhibited neurotoxicity induced by 2.4% isoflurane for 24 h in both primary cortical neurons and PC12 cells. This neuroprotection was most dramatically observed in matured cortical neurons (DIV 16) and PC12 cells with over expression of Alzheimer's mutated PS1 (L286V). Preconditioning L286V PC12 cells with equivalent two minimal alveolar concentrations (MAC) of halothane (1.5%), but not sevoflurane (4%), also abolished the neurotoxicity induced by 2.4% isoflurane for 24 h. Overall, these results suggest that isoflurane may be both neuroprotective and neurotoxic, depending on the exposure concentrations and duration.
 ...
PMID:Isoflurane preconditioning inhibited isoflurane-induced neurotoxicity. 1772 66

Pheochromocytoma is uncommon in children. We report herein a case in a 6-year-old boy whose pheochromocytoma was revealed by cerebral ischemia as a consequence of acute-cardiac failure. Twenty-four-hour urinary catecholamines were markedly increased. Abdominal ultrasonography and computed tomography located the tumor on the left adrenal gland. After surgical excision, hypertension disappeared. Diagnosis and treatment of pheochromocytoma in children are discussed.
 ...
PMID:[Pheochromocytoma revealed by stroke in a child]. 1880 78

L-glutamate plays a key role in neuronal cell death associated with many neurodegenerative conditions such as cerebral ischemia, hypoxia, Alzheimer's, Huntington's, and Parkinson's diseases. Selaginellin, a component extracted from Saussurea pulvinata (Hook.et Grev.) Maximo, was assessed for its ability to protect rat pheochromocytoma (PC12) cells against oxidative toxicity induced by glutamate. The differentiated PC12 cells were pretreated with various concentrations (10(-7), 3 x 10(-7), or 10(-6) M) of selaginellin for 1 h prior to exposure to L-glutamate. Selaginellin was shown to protect PC12 cells against glutamate toxicity, as determined by characteristic morphological features, lactate dehydrogenase release and cell viability, and apoptosis as evaluated by Hoechst 33342 staining assay and caspase-3 activity. In addition, the increase in levels of reactive oxygen species and decrease in klotho gene expression induced by glutamate were significantly reversed by selaginellin. Our study suggests that selaginellin has a neuroprotective effect against L-glutamate-induced neurotoxicity through mechanisms related to anti-oxidation and anti-apoptosis via scavenging reactive oxygen species and up-regulating the expression of klotho gene.
 ...
PMID:Protective effect of selaginellin on glutamate-induced cytotoxicity and apoptosis in differentiated PC12 cells. 1993 11


1 2 3 4 Next >>