Role of Poly-(ADP-Ribose) Polymerase in Transplant Acute Tubular Necrosis and Its Relationship With Delayed Renal Function

O’Valle, Francisco; Benítez, Maribel; Gómez‐Morales, Mercedes; Bravo, José A.; Osuna, Antonio; Moral, R. Del; Martín‐Oliva, David; Oliver, F. Javier; Moral, R.G. Del

doi:10.1016/j.transproceed.2005.02.040

Cited by 7 publications

(4 citation statements)

References 22 publications

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“…As mentioned above, overactivation of PARP represents an important mechanism of tissue damage in various pathological conditions related to OS 23 , 64 , 65 . Therefore, the activation of the PARP pathway as a consequence of increased OS and subsequent DNA strand breaks can be hypothesized to explain male infertility related with OS.…”

Section: Overactivation Of Parp In Male Reproductionmentioning

confidence: 98%

Role of poly(ADP-ribose) polymerases in male reproduction

Çelik-Özenci

Taşatargil

2013

Spermatogenesis

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Poly(ADP-ribose) polymerases (PARPs) are a family of enzymes involved in a wide variety of biological processes, including DNA repair and maintenance of genomic stability following genotoxic stress, and regulates the expression of various proteins at the transcriptional level as well as replication and differentiation. However, excessive activation of PARP has been shown to contribute to the pathogenesis of several diseases associated with oxidative stress (OS), which has been known to play a fundamental role in the etiology of male infertility. Based on the degree and type of the stress stimulus, PARP directs cells to specific fates (such as, DNA repair vs. cell death). A large volume of accumulated evidence indicates the presence of PARP and its homologs in testicular germ line cells and its activity may offer a key mechanism for keeping DNA integrity in spermatogenesis. On the other hand, a possible role of PARP overactivation in OS-induced male reproductive disorders and in human sperm is gaining significance in recent years. In this review, we focus on the findings about the importance of PARP-1 and PARP-2 in male reproduction and possible involvement of PARP overactivation in various clinical conditions associated with male infertility.

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Section: Overactivation Of Parp In Male Reproductionmentioning

confidence: 98%

Role of poly(ADP-ribose) polymerases in male reproduction

Çelik-Özenci

Taşatargil

2013

Spermatogenesis

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“…[27,28] Besides, a role for PARP in inflammation, which is a possible causative factor for renal damage during sepsis, has been reported. [29] Therefore, the activation of the PARP pathway as a consequence of increased oxidative stress and subsequent DNA strand breaks can be hypothesized to explain ARF in endotoxic shock. In this study, we investigated whether the pharmacological inhibition of PARP might be a therapeutically viable strategy in preventing the ARF during sepsis.…”

Section: Introductionmentioning

confidence: 99%

Poly (ADP-Ribose) Polymerase as a Potential Target for the Treatment of Acute Renal Injury Caused by Lipopolysaccharide

Taşatargil¹,

Aksoy²,

Dalaklıoğlu³

et al. 2008

Renal Failure

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Recent studies have clearly reported that there is a relationship between endotoxemia and acute renal injury. The aim of this study was to investigate whether treatment with the new potent PARP inhibitor PJ34 could prevent the acute renal injury induced by lipopolysaccharide (LPS). Endotoxemia was induced by LPS injection (10 mg/kg, i.v.). LPS increased blood urea nitrogen (BUN) levels from 22 ± 0.54 mg/dL to 45.7 ± 5.79 mg/dL (p < 0.05). The plasma creatinine levels were 0.38 ± 0.02 mg/dL and 0.47 ± 0.03 mg/dL for the control and LPS groups, respectively. In addition, urinary excretion of N-acetyl-β-dglucosaminidase (NAG, a marker of renal tubular damage) was increased after LPS injection. By light microscopy, structural renal damage was observed in the LPS-treated group. However, PJ34 treatment (10 mg/kg, i.p.) attenuated LPS-induced renal injury, as indicated by plasma BUN and creatinine levels, urinary NAG excretion, and renal histology. These results indicated that the overactivation of the PARP pathway may have a role in LPSinduced renal impairment. Hence, pharmacological inhibition of this pathway might be an effective intervention to prevent endotoxin-induced acute renal injury.

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“…In a previous study of patients with ATN, our group found that the kidneys tolerating a long period of cold ischemia had the highest levels of PARP-1 (cold ischemia <24 h, PARP-1 = 1.71±0.62 vs. cold ischemia ≥24 h, PARP-1 = 2.86±0.35). In fact, the lowest PARP-1 expression level (1–9% of tubular nuclei positive) was only observed in kidneys with less than 20 h of cold ischemia (mean, 16.36 h; range, 12–20 h) [26].…”

Section: Discussionmentioning

confidence: 90%

Poly[ADP-Ribose] Polymerase-1 Expression Is Related To Cold Ischemia, Acute Tubular Necrosis, and Delayed Renal Function In Kidney Transplantation

et al. 2009

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Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD) transplantation. Ischemia-reperfusion (IR) injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1) activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN).Materials and MethodsNuclear PARP-1 immunohistochemical expression was studied in 326 paraffin-embedded renal allograft biopsies (193 with different degrees of ATN and 133 controls) and in murine Parp-1 knockout model of IR injury.ResultsPARP-1 expression showed a significant relationship with cold ischemia time (r coefficient = 0.603), time to effective diuresis (r = 0.770), serum creatinine levels at biopsy (r = 0.649), and degree of ATN (r = 0.810) (p = 0.001, Pearson test). In the murine IR model, western blot showed an increase in PARP-1 that was blocked by Parp-1 inhibitor. Immunohistochemical study of PARP-1 in kidney allograft biopsies would allow early detection of possible delayed renal function, and the administration of PARP-1 inhibitors may offer a therapeutic option to reduce damage from IR in donor kidneys by preventing or minimizing ATN. In summary, these results suggest a pivotal role for PARP-1 in the ATN of renal transplantation. We propose the immunohistochemical assessment of PARP-1 in kidney allograft biopsies for early detection of a possible delayed renal function.

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Role of Poly-(ADP-Ribose) Polymerase in Transplant Acute Tubular Necrosis and Its Relationship With Delayed Renal Function

Cited by 7 publications

References 22 publications

Role of poly(ADP-ribose) polymerases in male reproduction

Role of poly(ADP-ribose) polymerases in male reproduction

Poly (ADP-Ribose) Polymerase as a Potential Target for the Treatment of Acute Renal Injury Caused by Lipopolysaccharide

Poly[ADP-Ribose] Polymerase-1 Expression Is Related To Cold Ischemia, Acute Tubular Necrosis, and Delayed Renal Function In Kidney Transplantation

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