The Role of the Adenosine Receptor Subtypes and Protein Kinase C in Ischemic Preconditioning in the in Vivo Cat Heart

ABSTRACT The protein kinase C (PKC) family regulates macrophage function involved in host defense against infection. In the case of Leishmania donovani infection, the impairment of PKC-mediated signaling is one of the crucial events for the establishment of parasite into the macrophages. Earlier reports established that C-C chemokines mediated protection against leishmaniasis via the generation of nitric oxide after 48 h. In this study, we investigated the role of MIP-1α and MCP-1 in the regulation of impaired PKC activity in the early hours (6 h) of infection. These chemokines restored Ca2+-dependent PKC activity and inhibited Ca2+-independent atypical PKC activity in L. donovani-infected macrophages under both in vivo and in vitro conditions. Pretreatment of macrophages with chemokines induced superoxide anion generation by activating NADPH oxidase components in infected cells. Chemokine administration in vitro induced the migration of infected macrophages and triggered the production of reactive oxygen species. In vivo treatment with chemokines significantly restricted the parasitic burden in livers as well as in spleens. Collectively, these results indicate a novel regulatory role of C-C chemokines in controlling the intracellular growth and multiplication of L. donovani, thereby demonstrating the antileishmanial properties of C-C chemokines in the disease process.

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Phosphorylation of human pleckstrin on Ser-113 and Ser-117 by protein kinase C

Biochemical Journal ◽

10.1042/bj3140937 ◽

1996 ◽

Vol 314 (3) ◽

pp. 937-942 ◽

Cited By ~ 16

Author(s):

Karen L. CRAIG ◽

Calvin B. HARLEY

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Phosphorylation Sites ◽

Wild Type ◽

Cos Cells ◽

Phospholipid Hydrolysis ◽

Kinase C

During platelet activation, receptor-coupled phospholipid hydrolysis stimulates protein kinase C (PKC) and results in the phosphorylation of several proteins, the most prominent being pleckstrin. Pleckstrin is composed of two repeated domains, now called pleckstrin homology (PH) domains, separated by a spacer region that contains several consensus PKC phosphorylation sites. To determine the role of PKC-dependent phosphorylation in pleckstrin function, we mapped the phosphorylation sites in vivo of wild-type and site-directed mutants of pleckstrin expressed in COS cells. Phosphorylation was found to occur almost exclusively on Ser-113 and Ser-117 within the sequence 108-KFARKS*TRRS*IRL-120. Phosphorylation of these sites was confirmed by phosphorylation of the corresponding wild-type and mutant synthetic peptides in vitro.

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Protein Kinase C and Gi/o Proteins Are Involved in Adenosine- and Ischemic Preconditioning—Mediated Renal Protection

Journal of the American Society of Nephrology ◽

10.1681/asn.v122233 ◽

2001 ◽

Vol 12 (2) ◽

pp. 233-240 ◽

Cited By ~ 1

Author(s):

H. THOMAS LEE ◽

CHARLES W. EMALA

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Opioid Receptors ◽

Pertussis Toxin ◽

Ischemic Preconditioning ◽

Clinical Problem ◽

Protective Effects ◽

Renal Protection ◽

Kinase C

Abstract. 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., Gi/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 Gi/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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Role of Intracellular Ca 2+ in Activation of Protein Kinase C During Ischemic Preconditioning

Circulation ◽

10.1161/01.cir.96.4.1257 ◽

1997 ◽

Vol 96 (4) ◽

pp. 1257-1265 ◽

Cited By ~ 35

Author(s):

Koichi Node ◽

Masafumi Kitakaze ◽

Hiroshi Sato ◽

Tetsuo Minamino ◽

Kazuo Komamura ◽

...

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Ischemic Preconditioning ◽

Kinase C ◽

Intracellular Ca

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The Cardioprotective Effect of Ischemic Preconditioning : Role of Adenosine and Protein Kinase C

Korean Circulation Journal ◽

10.4070/kcj.1997.27.10.1004 ◽

1997 ◽

Vol 27 (10) ◽

pp. 1004

Author(s):

Hyun Kim ◽

Dae-Joong Kim ◽

Sung-Soo Kim ◽

Bong-Jin Rah ◽

Ho-Dirk Kim

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Ischemic Preconditioning ◽

Cardioprotective Effect ◽

Kinase C

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Platelet-activating factor induces cardioprotection in isolated rat heart akin to ischemic preconditioning: role of phosphoinositide 3-kinase and protein kinase C activation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00599.2004 ◽

2005 ◽

Vol 288 (5) ◽

pp. H2512-H2520 ◽

Cited By ~ 30

Author(s):

Claudia Penna ◽

Giuseppe Alloatti ◽

Sandra Cappello ◽

Donatella Gattullo ◽

Giovanni Berta ◽

...

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Ischemic Preconditioning ◽

Platelet Activating Factor ◽

Left Ventricular ◽

Isolated Rat Heart ◽

Cardioprotective Effect ◽

Kinase C ◽

Phosphoinositide 3 Kinase

Ischemic preconditioning (IP) is a cardioprotective mechanism against myocellular death and cardiac dysfunction resulting from reperfusion of the ischemic heart. At present, the precise list of mediators involved in IP and the pathways of their mechanisms of action are not completely known. The aim of the present study was to investigate the role of platelet-activating factor (PAF), a phospholipid mediator that is known to be released by the ischemic-reperfused heart, as a possible endogenous agent involved in IP. Experiments were performed on Langendorff-perfused rat hearts undergoing 30 min of ischemia followed by 2 h of reperfusion. Treatment with a low concentration of PAF (2 × 10−11 M) before ischemia reduced the extension of infarct size and improved the recovery of left ventricular developed pressure during reperfusion. The cardioprotective effect of PAF was comparable to that observed in hearts in which IP was induced by three brief (3 min) periods of ischemia separated by 5-min reperfusion intervals. The PAF receptor antagonist WEB-2170 (1 × 10−9 M) abrogated the cardioprotective effect induced by both PAF and IP. The protein kinase C (PKC) inhibitor chelerythrine (5 × 10−6 M) or the phosphoinositide 3-kinase (PI3K) inhibitor LY-294002 (5 × 10−5 M) also reduced the cardioprotective effect of PAF. Western blot analysis revealed that following IP treatment or PAF infusion, the phosphorylation of PKC-ε and Akt (the downstream target of PI3K) was higher than that in control hearts. The present data indicate that exogenous applications of low quantities of PAF induce a cardioprotective effect through PI3K and PKC activation, similar to that afforded by IP. Moreover, the study suggests that endogenous release of PAF, induced by brief periods of ischemia and reperfusion, may participate to the triggering of the IP of the heart.

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The Role of Protein Kinase C in Ischemic Preconditioning

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.1996.tb33514.x ◽

1996 ◽

Vol 793 (1 Myocardial Pr) ◽

pp. 177-190 ◽

Cited By ~ 19

Author(s):

MAHIKO GOTO ◽

MICHAEL V. COHEN ◽

JAMES M. DOWNEY

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Ischemic Preconditioning ◽

Kinase C

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