Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal ischemic reperfusion (IR) injury is a significant clinical problem in anesthesia and surgery. Recently, it was demonstrated that both renal ischemic preconditioning (IPC) and systemic adenosine pretreatment protect against renal IR injury. In cardiac IPC, pertussis toxin-sensitive G-proteins (i.e., G(i/o)), protein kinase C (PKC), and ATP-sensitive potassium (K+(ATP)) channels are implicated in this protective signaling pathway. The aim of this study was to elucidate the signaling pathways that are responsible for renal protection mediated by both IPC and adenosine pretreatment. In addition, because A1 adenosine receptor antagonist failed to block renal IPC, whether activation of bradykinin, muscarinic, or opioid receptors can mimic renal IPC was tested because these receptors have been implicated in cardiac IPC. Rats were acutely pretreated with chelerythrine or glibenclamide, selective blockers of PKC and K+(ATP) channels, respectively, before IPC or adenosine pretreatment. Some rats were pretreated with pinacidil (K+(ATP)channel opener), bradykinin, methacholine, or morphine before renal ischemia. Twenty-four h later, plasma creatinine was measured. Separate groups of rats received pertussis toxin intraperitoneally 48 h before being subjected to the above protective protocols. IPC and adenosine pretreatment protected against renal IR injury. Pretreatment with pertussis toxin and chelerythrine abolished the protective effects of both renal IPC and adenosine. However, glibenclamide pretreatment had no effect on either renal IPC or adenosine-induced renal protection, indicating no apparent role for K+(ATP) channels. Moreover, pinacidil, bradykinin, methacholine, and morphine failed to protect renal function. Therefore, the conclusion is that cellular signal transduction pathways of renal IPC and adenosine pretreatment in vivo involve G(i/o) proteins and PKC but not K+(ATP) channels. Unlike cardiac IPC, bradykinin, muscarinic, and opioid receptors do not mediate renal IPC.
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PMID:Protein kinase C and G(i/o) proteins are involved in adenosine- and ischemic preconditioning-mediated renal protection. 1115 13

Acute as well as delayed ischemic preconditioning (IPC) provides protection against cardiac and neuronal ischemia reperfusion (IR) injury. This study determined whether delayed preconditioning occurs in the kidney and further elucidated the mechanisms of renal IPC in mice. Mice were subjected to IPC (four cycles of 5 min of ischemia and reperfusion) and then to 30 min of renal ischemia either 15 min (acute IPC) or 24 h (delayed IPC) later. Both acute and delayed renal IPC provided powerful protection against renal IR injury. Inhibition of Akt but not extracellular signal-regulated kinase phosphorylation prevented the protection that was afforded by acute IPC. Neither extracellular signal-regulated kinase nor Akt inhibition prevented protection that was afforded by delayed renal IPC. Pretreatment with an antioxidant, N-(2-mercaptopropionyl)-glycine, to scavenge free radicals prevented the protection that was provided by acute but not delayed renal IPC. Inhibition of protein kinase C or pertussis toxin-sensitive G-proteins attenuated protection from both acute and delayed renal IPC. Delayed renal IPC increased inducible nitric oxide synthase (iNOS) as well as heat-shock protein 27 synthesis, and the renal protective effects of delayed preconditioning were attenuated by a selective inhibitor of iNOS (l-N(6)[1-iminoethyl]lysine). Moreover, delayed IPC was not observed in iNOS knockout mice. Both acute and delayed IPC were independent of A(1) adenosine receptors (AR) as a selective A(1)AR antagonist failed to block preconditioning and acute and delayed preconditioning occurred in mice that lacked A(1)AR. Therefore, this study demonstrated that acute or delayed IPC provides renal protection against IR injury in mice but involves distinct signaling pathways.
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PMID:Ischemic preconditioning provides both acute and delayed protection against renal ischemia and reperfusion injury in mice. 1698 58

Platelet endothelial cell adhesion molecule-1 (PECAM-1) (CD31) is known to inhibit platelet function and thrombus formation. The mechanisms involved in PECAM-1's roles as a modulator of hemostasis are still not completely understood. We examined the role of PECAM-1 as a regulator of tissue factor (TF) expression, a known important inducer of thrombosis. Wildtype and CD31KO mice underwent transient (30 min) renal ischemia followed by 24 h re-perfusion and their kidneys assessed for apoptosis, fibrin formation, and tissue factor expression. CD31KO mice exhibited increased tubular epithelial and endothelial apoptosis, increased fibrin deposition, and tissue factor expression. Human umbilical vein endothelial cells (HUVEC) transfected with antisense (AS) PECAM-1 oligonucleotides to downregulate PECAM-1 expression, exhibited greater induction of TF mRNA and protein expression as well as increased expression and nuclear localization of the transcription factor Egr-1 compared to scrambled AS PECAM-1 (Scr)-treated HUVEC following thrombin stimulation. TF induction was found to be mediated through thrombin receptor PAR-1 and the Galphai/o subunit of G-protein, confirmed by PAR-1 antagonist and pertussis toxin inhibition respectively. Thrombin-mediated TF induction was dependent on Rho Kinase activity, phosphorylation of p38(MAPK) and p85 & Akt dephosphorylation. The inverse correlation of PI3K-Akt phosphorylation with p38 (MAPK) phosphorylation was confirmed by pharmacological inhibition. These studies suggest that PECAM-1 is involved in regulating a signaling pathway, affecting PI3K and Akt activation, p38 (MAPK) phosphorylation, which in turn, affects Egr-1 expression and nuclear translocation, ultimately affecting TF expression. These findings provide new insights into the action of PECAM-1 as a modulator of thrombosis.
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PMID:PECAM-1 modulates thrombin-induced tissue factor expression on endothelial cells. 1711 62

We showed previously that activation of A(1) adenosine receptors (AR) protects against renal ischemia-reperfusion (IR) injury in rats and mice. In the heart, transient A(1)AR activation produces biphasic protective effects: acute protection wanes after several hours but protective effects return 24-72 h later (second window of protection). In this study, we determined whether A(1)AR activation produces delayed renal protection and elucidated the mechanisms of acute and delayed renal protection. A(1)AR wild-type mice were subjected to 30-min renal ischemia and 24 h of reperfusion to produce acute renal failure. Pretreatment with a selective A(1)AR agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA; 0.1 mg/kg bolus ip) either 15 min or 24 h before renal ischemia protected against renal IR injury and reduced renal corticomedullary necrosis, apoptosis, and inflammation. Transient A(1)AR activation led to phosphorylation of extracellular signal-regulated protein kinase mitogen-activated protein kinase (ERK MAPK), Akt, and heat shock protein 27 (HSP27). Moreover, induction of HSP27 and Akt occurred with CCPA treatment. Inhibition of PKC with chelerythrine prevented acute but not delayed renal protection with A(1)AR activation. Moreover, deletion of PI3Kgamma or inhibition of Akt, but not inhibition of ERK, prevented delayed and acute renal protection with A(1)AR activation. Inhibition of G(i/o) with pertussis toxin obliterated both acute and delayed A(1)AR-mediated renal protection. In contrast to renal protection with delayed ischemic preconditioning, nitric oxide synthase activity was not induced with delayed A(1)AR-mediated renal protection. Therefore, transient activation of renal A(1)AR led to acute as well as delayed protective effects against renal IR injury via distinct signaling pathways.
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PMID:Acute and delayed renal protection against renal ischemia and reperfusion injury with A1 adenosine receptors. 1792 14