Pituitary adenylate cyclase activating polypeptide protects cardiomyocytes against oxidative stress-induced apoptosis

Gasz, Balázs; Rácz, Bóglárka; Röth, Erzsébet; Borsiczky, Balázs; Ferencz, A.; Tamás, Andrea; Cserepes, Barbara; Lubics, Andrea; Gallyas, Ferenc; Tóth, Gábor; Lengvári, Istvàn; Reglődi, Dóra

doi:10.1016/j.peptides.2005.06.022

Cited by 75 publications

(68 citation statements)

References 61 publications

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“…[29][30][31] In the present study, the number of TUNEL positive nuclei increased in PACAP+/-mice after Dox injection ( Figure 5C). This data indicates endogenous PACAP has anti-apoptotic effects in cardiac tissue.…”

Section: Pacap and Heart Diseasesupporting

confidence: 63%

Cardioprotective Effect of Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide on Doxorubicin-Induced Cardiomyopathy in Mice

Mori

Nakamachi

Ohtaki

et al. 2010

Circ J

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Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp ituitary adenylate cyclase-activating polypeptide (PACAP) is a regulatory peptide that was first isolated from the ovine hypothalamus. 1 PACAP exists in 2 amidated forms of either 38 and 27 residues, designated PACAP38 and PACAP27, respectively. 2 PACAP is a member of the vasoactive intestinal polypeptide (VIP)/secretin/ growth hormone releasing hormone family of peptides, and its amino acid sequence shows great similarity to VIP.PACAP and VIP share 3 kinds of receptors, namely PAC1-receptor (PAC1R), and the VPAC1 and VPAC2 receptors. The affinity of PAC1R with PACAP is 100-1,000 times higher than with VIP, indicating that PAC1R is a relatively selective receptor for PACAP. 3 PACAP is widely distributed in the brain and peripheral organs in mammals, and reportedly has diverse functions in the endocrine, nervous, gastrointestinal, immune, and cardiovascular systems. 4,5 PACAP and its receptors have also been identified in mammalian heart. 6-11 PACAP modulates the excitability of intracardiac neurons 6,12,13 and has positive inotropic, chronotropic, and dromotoropic effects on cardiomyocyte. 14-16 PACAP is also a potent vasodilator in various organs, including coronary and pulmonary arteries. PACAP and its receptors are expressed in the heart, but it is unclear whether PACAP exerts its protective effect on the myocardium in vivo. The aim of the present study was to investigate whether endogenous PACAP has a cardioprotective effect on Doxorubicin (Dox)-induced cardiomyopathy.

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Section: Pacap and Heart Diseasesupporting

confidence: 63%

Cardioprotective Effect of Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide on Doxorubicin-Induced Cardiomyopathy in Mice

Mori

Nakamachi

Ohtaki

et al. 2010

Circ J

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“…PACAP can protect cardiomyocytes against oxidative stress-induced apoptosis (Gasz et al, 2006). Thus, PACAP production and secretion by regenerating cardiac neurons in vivo could be beneficial to both the cardiac neurons and cardiac muscle following injury.…”

Section: Discussionmentioning

confidence: 99%

Regulation of neuronal pituitary adenylate cyclase-activating polypeptide expression during culture of guinea-pig cardiac ganglia

et al. 2007

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The trophic neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) increases in many different neuron types following injury; a response postulated to support cell survival and regeneration. In acutely isolated cardiac ganglia, approximately 1% of the cardiac neurons exhibited PACAP immunoreactivity whereas after 72 hours in culture, ~25% of the neurons were PACAP immunoreactive. In contrast, there was no increase in vasoactive intestinal polypeptide (VIP)-immunoreactive (IR) cells. Using a combination of immunocytochemical and molecular techniques, we have quantified PACAP expression, during explant culture of guinea pig cardiac ganglia. Using real time PCR, PACAP transcript levels increased progressively up to 48 hours in culture with no further increase after 72 hours. PACAP transcript levels were reduced by neurturin at 48 hours in culture but not after 24 or 72 hours in culture. In addition, neurturin partially suppressed the percentage of PACAP-IR neurons after 72 hours in culture, an effect mediated by activation of the phosphatidylinositol 3-kinase and mitogen activated protein kinase signaling pathways. The addition of different known regulatory molecules, including CNTF, Il-1β, TNFα, bFGF, TGF βand NGF did not increase the percentage of PACAP-IR neurons after 24 hours in culture; a result indicating that the generation and secretion of these factors did not stimulate PACAP expression. The presence of 20 nM PACAP or 10 μM forskolin increased the percentage of PACAP-IR cardiac neurons in 24 hour cultures, but not in 72 hour cultures. Neither treatment enhanced the number of VIP-IR neurons. The addition of the PAC 1 receptor antagonist, M65 (100 nM) suppressed the 20 nM PACAP-induced increase in percentage of PACAP-IR cells in 24 hour cultures indicating the effect of PACAP was mediated through the PAC 1 receptor. However, 100 nM M65 had no effect on the percentage of PACAP-IR cells in either 24 or 48 hour cultures not treated with exogenous PACAP, suggesting that endogenous release of PACAP likely did not contribute to the enhanced peptide expression. We postulate that the enhanced PACAP expression, which occurs in response to injury is facilitated in the explant cultured cardiac ganglia by the loss of a target-derived inhibitory factor, very likely neurturin. In intact tissues the presence of neurturin would normally suppress PACAP expression. Lastly, our results indicate that many common trophic factors do not enhance PACAP expression in the cultured cardiac neurons. However, the stimulatory role of an, as yet, unidentified factor can not be excluded. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content...

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“…PACAP also exhibits protective properties against oxidative stress-induced apoptosis in cardiomyocytes (Gasz et al, 2006;Rá cz et al, 2008;Roth et al, 2009) and endothelial cells (Rá cz et al, 2007), pointing to the therapeutic interest of PACAP for the treatment of cardiovascular diseases.…”

mentioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

et al. 2009

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Pituitary adenylate cyclase activating polypeptide protects cardiomyocytes against oxidative stress-induced apoptosis

Cited by 75 publications

References 61 publications

Cardioprotective Effect of Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide on Doxorubicin-Induced Cardiomyopathy in Mice

Cardioprotective Effect of Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide on Doxorubicin-Induced Cardiomyopathy in Mice

Regulation of neuronal pituitary adenylate cyclase-activating polypeptide expression during culture of guinea-pig cardiac ganglia

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

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