Pituitary adenylate cyclase-activating polypeptide ameliorates cisplatin-induced acute kidney injury

Li, Min; Balamuthusamy, Saravanan; Khan, Altaf M.; Maderdrut, Jerome L.; Simon, Eric E.; Batuman, Vecihi

doi:10.1016/j.peptides.2009.12.018

Cited by 26 publications

(30 citation statements)

References 55 publications

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“…Apoptosis plays an important role in ischemia/reperfusion-induced kidney injury [40]. The antiapoptotic effect of PACAP in the kidney had already been proven in cisplatin-and in cyclosporin-induced kidney injury [21,28]. We found a significant decrease of the antiapoptotic Bcl-2 after renal ischemia/reperfusion, reversed by PACAP treatment [15].…”

Section: Effect Of Exogenous Pacap In Ischemia/reperfusion-induced Kimentioning

confidence: 52%

“…In cisplatin-induced kidney injury the administration of PACAP reduced the increased level of blood urea nitrogen and serum creatinine, decreased apoptosis and the severity of the renal morphological changes. Increase of the level of TNF-α both in the plasma and in the kidney could be counteracted by PACAP treatment [28,30]. several studies have reported the protective effect of pacap in myeloma nephropathy [2,3,[25][26][27].…”

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confidence: 99%

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The effects of pituitary adenylate cyclase activating polypeptide in renal ischemia/reperfusion

László¹,

Kiss²,

Horváth³

et al. 2014

Acta Biologica Hungarica

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pituitary adenylate cyclase activating polypeptide (pacap) is a multifunctional neuropeptide occurring in the nervous system as well as in the peripheral organs. Beneficial action of PACAP has been shown in different pathological processes. The strong protective effects of the peptide are probably due to its complex modulatory actions in antiapoptotic, anti-inflammatory and antioxidant pathways. In the kidney, PACAP is protective in models of diabetic nephropathy, myeloma kidney injury, cisplatin-, gentamycinand cyclosporin-induced damages. Numerous studies have been published describing the protective effect of this peptide in renal ischemia/reperfusion. the present review focuses on the ischemia/reperfusioninduced kidney injury and gives a brief summary about the results published in this area.

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Section: Effect Of Exogenous Pacap In Ischemia/reperfusion-induced Kimentioning

confidence: 52%

mentioning

confidence: 99%

The effects of pituitary adenylate cyclase activating polypeptide in renal ischemia/reperfusion

László¹,

Kiss²,

Horváth³

et al. 2014

Acta Biologica Hungarica

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“…After demonstrating that PACAP38 has an inhibitory effect against cisplatin-induced apoptosis both in vivo and in vitro [17,18], we attempted to mimic I/R in cell cultures by covering cell layers with mineral oil for hypoxia-reoxygenation in primary cultures of renal PTEC from wild-type and MyD88 –/– mice. PACAP38 (10 –8 M ) was added 1 h before subjecting cells to hypoxia.…”

Section: Resultsmentioning

confidence: 99%

“…PACAP38 (10 –8 M ) was added 1 h before subjecting cells to hypoxia. The effect of PACAP38 on tubule cell apoptosis was monitored by fluorescence-activated cell sorting analysis as described previously [17,18]. The fraction of active fluorescein isothiocyanate (FITC)-labeled annexin V-positive (apoptotic) cells was increased significantly from 3.3 to 23.1% by hypoxia, but was reduced sharply from 23.1 to 6.5% by PACAP38 treatment (fig.…”

Section: Resultsmentioning

confidence: 99%

“…We also used primary cultures of murine proximal tubule cells from wild-type and MyD88 –/– mice that were subjected to ischemia/hypoxia. We recently observed that the 38-amino-acid form of pituitary adenylate cyclase-activating polypeptide (PACAP38) prevents renal tubule injury by modulating inflammatory responses in various kidney injury models, including cisplatin nephrotoxicity in vitro and in vivo [17,18]. In the present study, we explored the renoprotective properties of PACAP38 in the I/R model of AKI and the interaction of PACAP38 with inflammatory pathways involving innate immunity through the TLR4- and MyD88-mediated pathways.…”

Section: Introductionmentioning

confidence: 99%

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The Effect of PACAP38 on MyD88-Mediated Signal Transduction in Ischemia-/Hypoxia-Induced Acute Kidney Injury

Khan

Maderdrut

et al. 2010

Am J Nephrol

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Background/Aims: Toll-like receptor 4 (TLR4) and its adaptor protein MyD88 play an important role in ischemia/reperfusion (I/R) injury in the kidney, and pituitary adenylate cyclase-activating polypeptide (PACAP) could ameliorate renal I/R injury. Methods: Primary cultures of proximal tubule epithelial cells (PTEC) were prepared from wild-type and MyD88^–/– mice, and subjected to hypoxia in vitro. Acute kidney injury (AKI) was induced by I/R in vivo in wild-type mice only. Results: Hypoxia resulted in significant increases in cytokine production and apoptosis/necrosis in wild-type PTEC, but these responses were markedly blunted in MyD88^–/– PTEC. Treatment with PACAP38 before or after hypoxia further suppressed the hypoxia-induced cytokine responses and apoptosis in both MyD88^+/+ and MyD88^–/– PTEC cultures. PACAP38 significantly inhibited TLR4/MyD88/TRAF6 as well as TRIF and IRF3 expression in mouse kidney and PTEC, and inhibited the secretion and mRNA expression of cytokines in kidneys from mice after I/R, paralleling the cytokine responses in vitro. Moreover, treatment with PACAP38 protected mice from renal failure, histological damage, neutrophil influx and tubule cell apoptosis after I/R. Conclusion: Our data reveal that the TLR4-mediated cytokine responses to hypoxia are primarily dependent on MyD88 signaling and highlight the pivotal role of MyD88-dependent mechanisms in the coordination of the innate immune responses to ischemic/hypoxic acute renal tubular injury. The renoprotective effect of PACAP in AKI involves both MyD88-dependent and -independent pathways.

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Renoprotective Effects of Pituitary Adenylate Cyclase-Activating Polypeptide 38 (PACAP38)

Khan

Batuman

2016

Current Topics in Neurotoxicity

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Pituitary adenylate cyclase-activating polypeptide ameliorates cisplatin-induced acute kidney injury

Cited by 26 publications

References 55 publications

The effects of pituitary adenylate cyclase activating polypeptide in renal ischemia/reperfusion

The effects of pituitary adenylate cyclase activating polypeptide in renal ischemia/reperfusion

The Effect of PACAP38 on MyD88-Mediated Signal Transduction in Ischemia-/Hypoxia-Induced Acute Kidney Injury

Renoprotective Effects of Pituitary Adenylate Cyclase-Activating Polypeptide 38 (PACAP38)

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