Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute pancreatitis is a multifactorial disease associated with the premature activation of digestive enzymes. The genes expressed in pancreatic acinar cells determine the severity of the disease. The present study determined the differentially expressed genes in pancreatic acinar cells treated with cerulein as an in vitro model of acute pancreatitis. Pancreatic acinar AR42J cells were stimulated with 10(-8) M cerulein for 4 h, and genes with altered expression were identified using a cDNA microarray for 4,000 rat genes and validated by real-time PCR. These genes showed a 2.5-fold or higher increase with cerulein: lithostatin, guanylate cyclase, myosin light chain kinase 2, cathepsin C, progestin-induced protein, and pancreatic trypsin 2. Stathin 1 and ribosomal protein S13 showed a 2.5-fold or higher decreases in expression. Real-time PCR analysis showed time-dependent alterations of these genes. Using commercially available antibodies specific for guanylate cyclase, myosin light chain kinase 2, and cathepsin C, a time-dependent increase in these proteins were observed by Western blotting. Thus, disturbances in proliferation, differentiation, cytoskeleton arrangement, enzyme activity, and secretion may be underlying mechanisms of acute pancreatitis.
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PMID:Altered gene expression in cerulein-stimulated pancreatic acinar cells: pathologic mechanism of acute pancreatitis. 2005 85

Carbon monoxide (CO) is known as an essential gaseous messenger that regulates a wide array of physiological and pathological processes, similar to nitric oxide (NO) and hydrogen sulfide. The aim of the present study was to elucidate the potential role of CO in Ca(2+) homeostasis and to explore the underlying mechanisms in pancreatic acinar cells. The exogenous application of a CO-releasing molecule dose-dependently increased intracellular Ca(2+) concentration ([Ca(2+)]i). A heme oxygenase (HO) inducer increased [Ca(2+)]i in a concentration-dependent manner, and the increase was diminished by an HO inhibitor. The CO-induced [Ca(2+)]i increase persisted in the absence of extracellular Ca(2+), indicating that Ca(2+) release is the initial source for the increase. The inhibition of G protein, phospholipase C (PLC), and inositol 1,4,5-trisphosphate (IP3) receptor diminished the CO-induced [Ca(2+)]i increase. CO upregulated endothelial nitric oxide synthase (eNOS) expression and stimulated NO production, and NOS inhibitor, calmodulin inhibitor, or the absence of extracellular Ca(2+) eliminated the latter response. Blocking the phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) pathway abolished CO-induced NO production. Pretreatment with an NOS inhibitor, NO scavenger, or soluble guanylate cyclase inhibitor, did not affect the CO-induced [Ca(2+)]i increase, indicating that NO, soluble guanylate cyclase, and cyclic guanosine 5'-monophosphate are not involved in the CO-induced [Ca(2+)]i increase. CO inhibited the secretory responses to CCK-octapeptide or carbachol. We conclude that CO acts as a regulator not only for [Ca(2+)]i homeostasis via a PLC-IP3-IP3 receptor cascade but also for NO production via the calmodulin and PI3K-Akt/PKB pathway, and both CO and NO interact. Moreover, CO may provide potential therapy to ameliorate acute pancreatitis by inhibiting amylase secretion.
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PMID:A novel role for carbon monoxide as a potent regulator of intracellular Ca2+ and nitric oxide in rat pancreatic acinar cells. 2525 50