Sentrin-specific protease 1 maintains mitochondrial homeostasis through targeting the deSUMOylation of sirtuin-3 to alleviate oxidative damage induced by hepatic ischemia/reperfusion.

Hepatic ischemia/reperfusion injury (HIRI) represents a prevalent pathophysiological process that imposes a substantial economic burden in clinical practice, especially in liver surgery. Sentrin-specific protease 1 (SENP1) is a crucial enzyme involved in the regulation of SUMOylation, and is related to various diseases. However, the role of SENP1 in HIRI remains unexplored. Here, we confirmed that SENP1 actively participated in modulating the oxidative damage induced by HIRI. Notably, SENP1 functioned by maintaining mitochondrial homeostasis. Further mechanistic exploration indicated that the protective mitochondrial protein sirtuin-3 (Sirt3) was inactivated by SUMOylation during HIRI, which was reversed by SENP1. Overexpression of SENP1 could restore mitochondrial function, mitigate oxidative stress and attenuated apoptosis through recovering the expression of Sirt3 during HIRI. Nevertheless, 3-TYP, an inhibitor of Sirt3, could eliminate the therapeutic effects brought by overexpression of SENP1. In conclusion, our findings demonstrated that SENP1 mediated the deSUMOylation of Sirt3 and maintained mitochondrial homeostasis, thus alleviating HIRI induced oxidative damage. SENP1 might be a promising therapeutic target for HIRI.

Hepatocellular SETDB1 Regulates Hepatic Ischemia-Reperfusion Injury through Targeting Lysine Methylation of ASK1 Signal.

Background: Hepatic ischemia-reperfusion injury (HIRI) stands as an unavoidable complication arising from liver surgery, profoundly intertwined with its prognosis. The role of lysine methyltransferase SET domain bifurcated 1 (SETDB1) in HIRI remains elusive, despite its confirmation as a potential therapeutic target for diverse diseases. Here, we investigated the mechanism by which SETDB1 regulated HIRI. Methods: RNA sequencing data were used to identify the expression and potential targets of SETDB1 through bioinformatics analysis. To elucidate the impact of SETDB1 on HIRI, both an in vivo model of HIRI in mice and an in vitro model of hepatocyte hypoxia/reoxygenation were established. Biochemical and histological analyses were used to investigate the influence of SETDB1 on liver damage mediated by HIRI. Chromatin immunoprecipitation and coimmunoprecipitation were implemented to explore the in-depth mechanism of SETDB1 regulating HIRI. Results: We confirmed that hepatocellular SETDB1 was up-regulated during HIRI and had a close correlation with HIRI-related inflammation and apoptosis. Moreover, inhibition of SETDB1 could mitigate HIRI-induced liver damage, inflammation, and apoptosis. Through our comprehensive mechanistic investigation, we revealed that SETDB1 interacts with apoptosis-signal-regulating kinase 1 (ASK1) and facilitates the methylation of its lysine residues. Inhibition of SETDB1 resulted in reduced phosphorylation of ASK1, leading to a marked suppression of downstream c-Jun N-terminal kinase (JNK)/p38 signaling pathway activation. The therapeutic effect on inflammation and apoptosis achieved through SETDB1 inhibition was nullified by the restoration of JNK/p38 signaling activation through ASK1 overexpression. Conclusions: The findings from our study indicate that SETDB1 mediates lysine methylation of ASK1 and modulates the activation of the ASK1-JNK/p38 pathway, thus involved in HIRI-induced inflammation and apoptosis. These results suggest that SETDB1 holds promise as a potential therapeutic target for mitigating HIRI.

A comprehensive survival and prognosis analysis of GPR55 expression in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common subtype, accounting for about 90% of all primary liver cancers. The liver is rich in a large number of immune cells, thus forming a special immune microenvironment, which plays a key role in the occurrence and development of hepatocellular carcinoma. Nowadays, tumor immunotherapy has become one of the most promising cancer treatment methods. Immune checkpoint inhibitors (ICIs) combined with VEGF inhibitors are listed as first-line treatment options for advanced HCC. Therefore, the search for a potential biomarker to predict the response to immunotherapy in HCC patients is urgently needed. The G protein-coupled receptor 55 (GPR55), a lysophosphatidylinositol (LPI) receptor, has recently emerged as a potential new target for anti-tumor therapy. Previous studies have found that GPR55 is highly expressed in breast cancer, pancreatic cancer, skin cancer and cholangiocarcinoma, and is involved in tumor proliferation and migration. However, the role and mechanism of GPR55 in HCC has not been elucidated. Therefore, this article discusses the clinical significance of GPR55 in HCC and its correlation with the immune response of HCC patients, so as to provide theoretical basis for improving the prognosis of HCC.

NCOA7 Regulates Growth and Metastasis of Clear Cell Renal Cell Carcinoma via MAPK/ERK Signaling Pathway.

NCOA7 is a nuclear receptor coactivator that is downregulated in a variety of cancers. However, the expression and prognostic significance of NCOA7 in clear cell renal cell carcinoma (ccRCC) remain unknown. The expression of NCOA7 in ccRCC tissues was analyzed using bioinformatics analysis, Western blotting, and immunohistochemistry. Kaplan-Meier analysis, the receiver operating characteristic (ROC) curve, and clinicopathological correlation analysis were used to assess the predictive power of NCOA7. Overexpression function tests were conducted in cells and mouse models to clarify the function and mechanism of NCOA7 in inhibiting the progression of ccRCC. NCOA7 expression was downregulated in all three subtypes of renal cell carcinoma, and only had significant prognostic value for patients with ccRCC. NCOA7 overexpression inhibited the proliferation, invasion, and metastasis of ccRCC cells in vivo and in vitro. Mechanistically, NCOA7 inhibited the MAPK/ERK pathway to regulate epithelial-mesenchymal transformation (EMT) and apoptosis, thereby inhibiting the progression of ccRCC. NCOA7 inhibits tumor growth and metastasis of ccRCC through the MAPK/ERK pathway, thus indicating its potential as a prognostic marker and therapeutic target for ccRCC.

Ubiquitin-specific protease 29 attenuates hepatic ischemia-reperfusion injury by mediating TGF-ß-activated kinase 1 deubiquitination.

Background and aims: In the course of clinical practice, hepatic ischemia/reperfusion (I/R) injury is a prevalent pathophysiological event and is caused by a combination of complex factors that involve multiple signaling pathways such as MAPK and NF-κB. USP29 is a deubiquitinating enzyme important during the development of tumors, neurological diseases, and viral immunity. However, it is unknown how USP29 contributes to hepatic I/R injury. Methods and results: We systematically investigated the role of the USP29/TAK1-JNK/p38 signaling pathway in hepatic I/R injury. We first found reduced USP29 expression in both mouse hepatic I/R injury and the primary hepatocyte hypoxia-reoxygenation (H/R) models. We established USP29 full knockout mice (USP29-KO) and hepatocyte-specific USP29 transgenic mice (USP29-HTG), and we found that USP29 knockout significantly exacerbates the inflammatory infiltration and injury processes during hepatic I/R injury, whereas USP29 overexpression alleviates liver injury by decreasing the inflammatory response and inhibiting apoptosis. Mechanistically, RNA sequencing results showed the effects of USP29 on the MAPK pathway, and further studies revealed that USP29 interacts with TAK1 and inhibits its k63-linked polyubiquitination, thereby preventing the activation of TAK1 and its downstream signaling pathways. Consistently, 5z-7-Oxozeaneol, an inhibitor of TAK1, blocked the detrimental effects of USP29 knockout on H/R-induced hepatocyte injury, further confirming that USP29 plays a regulatory role in hepatic I/R injury by targeting TAK1. Conclusion: Our findings imply that USP29 is a therapeutic target with promise for the management of hepatic I/R injury via TAK1-JNK/p38 pathway-dependent processes.

A case report of two Chinese monozygotic twins with NPHP1 gene-associated nephronophthisis undergoing kidney transplantation from a related living-donor.

BACKGROUND: Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease and the most common hereditary disease leading to end-stage renal disease in children and adolescents. The NPHP1 gene was the first NPHP gene to be discovered. Pathogenic variation of the NPHP1 gene can cause juvenile renal wasting disease type 1. CASE PRESENTATION: Here, we report the first case of living related kidney transplantation of monozygotic twins with NPHP1 nephronophthisis in China; one of these cases involved cross-blood type kidney transplantation. Our experience shows that patients with NPHP1 nephronophthisis have almost no risk recurrent kidney disease following living related kidney transplantation and genetic testing. The two twins recovered well without any complications. CONCLUSIONS: This is the first report of living related kidney transplantation of monozygotic twins with heterozygous deletion of the NPHP1 gene in a Chinese family with NPHP. In addition, genetic testing provides an efficient means of evaluating the safety of living related kidney transplantation in patients with NPHP1 nephronophthisis.

Correlation between CYP3A5 gene polymorphism and BK virus infection in kidney transplant recipients.

BACKGROUND: Cytochrome P450 3A5 (CYP3A5) includes two active genotypes, namely CYP3A5*1/*1 or *1/*3 with the fast metabolic activity and CYP3A5*3/*3 with slow metabolic. We retrospectively analyzed the correlation between CYP3A5 gene polymorphism and the susceptibility to the BK virus (BKV) infection in renal transplant recipients. METHODS: According to the inclusion/ exclusion criteria, we selected 134 recipients who received kidney transplantation at the Renmin Hospital of Wuhan University from January 2019 to December 2019. Based on the pre-operative CYP3A5 sequencing results, 134 recipients were divided into two groups: those expressing the fast metabolic CYP3A5*1/*1 or *1/*3 genotype; and, those expressing slow metabolic CYP3A5*3/*3 genotype. These two recipient groups were then analyzed for the BKV infection rate with different metabolic types to establish the potential relationship between CYP3A5 gene polymorphism and BKV infection. RESULTS: The overall incidence of BKV viruria was 37.3%, whereas BKV viremia was 4.5% among all 134 recipients. The fast metabolism group had 9.1% incidence of BKV viremia and 49.1% incidence of BKV viruria. In contrast, the slow metabolism group had only 1.3%incidence of BKV viremia (P = 0.031) with only 29.1% BKV viruria (P = 0.011). The incidence of low levels of urinary BKV in the fast metabolism group was higher than that in the slow metabolism group (P = 0.005), while no significant statistical difference in the incidence of high levels of urinary BKV and high and low levels of blood BKV. CONCLUSION: After kidney transplantation, CYP3A5 gene polymorphism of recipients present a certain relationship with the occurrence of BKV infection, which may be of value for the prediction and prevention of BKV infection.

Clinical characteristics of tuberculous infection following renal transplantation.

OBJECTIVE: This study investigated the clinical characteristics of patients with tuberculosis (TB) following renal transplantation (RT) in order to identify markers or signs that can facilitate early diagnosis. METHODS: A retrospective analysis was performed on 12 cases of Mycobacterium tuberculosis infection treated at our hospital between 2005 and 2020. RESULTS: The incidence of TB after RT at our hospital was 0.9%, and the median postoperative onset time was 22 months. The average age of patients included in our analysis was 44.2 ± 9.4 years; 11 of the 12 patients were male, and most patients had (low) fever as the first or only manifestation. Five patients had respiratory symptoms; 5 had typical computed tomography (CT) presentation; and 2 had a confirmed history of TB. Two sputum smears from 12 patients were positive by acid fast staining, and M. tuberculosis was detected in peripheral blood samples by metagenomic next-generation sequencing (NGS). One patient had a positive result in the purified protein derivative (PPD) test, 7 were positive with the interferon gamma release assay (IGRA), 8/12 patients were confirmed to have TB infection by NGS and 1 was confirmed positive by lung biopsy. CONCLUSION: Because of the use of immunosuppressive agents, most patients with TB following RT have atypical clinical symptoms and CT findings, and may have a high probability of a false negative result with the traditional PPD test and a low probability of M. tuberculosis detection, making early diagnosis difficult. Therefore, in RT recipients with prolonged fever of unknown origin and unusual clinical manifestations, especially those who are unresponsive to antibiotic treatment, a diagnosis of TB should be considered. The interferon gamma release assay and NGS are relatively new detection methods with high sensitivity and specificity; these along with regular, repeated testing by various approaches can aid the early diagnosis of TB.

N-acetylgalactosaminyltransferase-4 protects against hepatic ischemia/reperfusion injury by blocking apoptosis signal-regulating kinase 1 N-terminal dimerization.

BACKGROUND AND AIMS: Ischemia-reperfusion (I/R) injury is an inevitable complication of liver transplantation (LT) and compromises its prognosis. Glycosyltransferases have been recognized as promising targets for disease therapy, but their roles remain open for study in hepatic I/R (HIR) injury. Here, we aim to demonstrate the exact function and molecular mechanism of a glycosyltransferase, N-acetylgalactosaminyltransferase-4 (GALNT4), in HIR injury. APPROACH AND RESULTS: By an RNA-sequencing data-based correlation analysis, we found a close correlation between GALNT4 expression and HIR-related molecular events in a murine model. mRNA and protein expression of GALNT4 were markedly up-regulated upon reperfusion surgery in both clinical samples from subjects who underwent LT and in a mouse model. We found that GALNT4 deficiency significantly exacerbated I/R-induced liver damage, inflammation, and cell death, whereas GALNT4 overexpression led to the opposite phenotypes. Our in-depth mechanistic exploration clarified that GALNT4 directly binds to apoptosis signal-regulating kinase 1 (ASK1) to inhibit its N-terminal dimerization and subsequent phosphorylation, leading to a robust inactivation of downstream c-Jun N-terminal kinase (JNK)/p38 and NF-κB signaling. Intriguingly, the inhibitory capacity of GALNT4 on ASK1 activation is independent of its glycosyltransferase activity. CONCLUSIONS: GALNT4 represents a promising therapeutic target for liver I/R injury and improves liver surgery prognosis by inactivating the ASK1-JNK/p38 signaling pathway.

DUSP12 protects against hepatic ischemia-reperfusion injury dependent on ASK1-JNK/p38 pathway in vitro and in vivo.

Hepatic ischemia-reperfusion (I/R) injury is an important risk factor resulting in liver failure during liver surgery. However, there is still lack of effective therapeutic methods to treat hepatic I/R injury. DUSP12 is a member of the dual specific phosphatase (DUSP) family. Some DUSPs have been identified as being involved in the regulation of hepatic I/R injury. However, the role of DUSP12 during hepatic I/R injury is still unclear. In the present study, we observed a significant decrease in DUSP12 expression in a hepatic I/R injury mouse model in vivo and in hypoxia/reoxygenation (H/R) model in vitro. Using hepatocyte-specific DUSP12 knockout mice and DUSP12 transgenic mice, we demonstrated that DUSP12 apparently relieved I/R-induced liver injury. Moreover, DUSP12 inhibited hepatic inflammatory responses and alleviated apoptosis both in vitro and in vivo. Furthermore, we demonstrated that JNK and p38 activity, but not ERK1/2, was increased in the DUSP12-deficient mice and decreased in the DUSP12 transgenic mice under I/R condition. ASK1 was required for DUSP12 function in hepatic I/R injury and inhibition of ASK1 prevented inflammation and apoptosis in DUSP12-deficient hepatocytes and mice. In conclusion, DUSP12 protects against hepatic I/R injury and related inflammation and apoptosis. This regulatory role of DUSP12 is primarily through ASK1-JNK/p38 signaling pathway. Taken together, DUSP12 could be a potential therapeutic target for hepatic I/R injury.

Ubiquitin-specific protease-44 inhibits the proliferation and migration of cells via inhibition of JNK pathway in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney cancer. Ubiquitin-specific protease (USP)44 has been reported to be involved in various cancers. We investigated the function, role and molecular mechanism of USP44 in ccRCC. METHODS: Data obtained from the Cancer Genome Atlas Data Portal and Gene Expression Omnibus database were analyzed to uncover the clinical relevance of USP44 expression and tumor development. USP44 function in the proliferation and migration of tumor cells was assessed by cellular and molecular analyses using ccRCC lines (786-O cells and Caki-1 cells). RESULTS: USP44 showed low expression in ccRCC cancer tissues compared with that in normal tissue. USP44 expression was negatively correlated with tumor stage, tumor grade, and patient survival. USP44 overexpression inhibited the proliferation and migration of 786-O cells and Caki-1 cells significantly. USP44 overexpression also prohibited cell proliferation by upregulating expression of P21, downregulating cyclin-D1 expression, and inhibiting cell migration by downregulating expression of matrix metalloproteinase (MMP)2 and MMP9. USP44 knockdown enhanced the proliferation and migration of 786-O cells and Caki-1 cells. USP44 function in inhibiting the proliferation and migration of 786-O cells and Caki-1 cells was associated with phosphorylation of Jun N-terminal kinase (JNK). CONCLUSION: USP44 may be a marker in predicting ccRCC progression. Inhibition by USP44 of the proliferation and migration of 786-O cells and Caki-1 cells is dependent upon the JNK pathway.

Leukocyte immunoglobulin-like receptor B4 deficiency exacerbates acute lung injury via NF-κB signaling in bone marrow-derived macrophages.

Acute lung injury (ALI) is an acute inflammatory disease. Leukocyte immunoglobulin-like receptor B4 (LILRB4) is an immunoreceptor tyrosine-based inhibitory motif (ITIM)-bearing inhibitory receptor that is implicated in various pathological processes. However, the function of LILRB4 in ALI remains largely unknown. The aim of the present study was to explore the role of LILRB4 in ALI. LILRB4 knockout mice (LILRB4 KO) were used to construct a model of ALI. Bone marrow cell transplantation was used to identify the cell source of the LILRB4 deficiency-aggravated inflammatory response in ALI. The effect on ALI was analyzed by pathological and molecular analyses. Our results indicated that LILRB4 KO exacerbated ALI triggered by LPS. Additionally, LILRB4 deficiency can enhance lung inflammation. According to the results of our bone marrow transplant model, LILRB4 regulates the occurrence and development of ALI by bone marrow-derived macrophages (BMDMs) rather than by stromal cells in the lung. The observed inflammation was mainly due to BMDM-induced NF-κB signaling. In conclusion, our study demonstrates that LILRB4 deficiency plays a detrimental role in ALI-associated BMDM activation by prompting the NF-κB signal pathway.

Allopurinol preconditioning attenuates renal ischemia/reperfusion injury by inhibiting HMGB1 expression in a rat model.

PURPOSE: To investigate the potential effects of pretreatment with allopurinol on renal ischemia/reperfusion injury (IRI) in a rat model. METHODS: Twenty four rats were subjected to right kidney uninephrectomy were randomly distributed into the following three groups (n=8): Group A (sham-operated group); Group B (ischemic group) with 30 min of renal ischemia after surgery; and Group C (allopurinol + ischemia group) pretreated with allopurinol at 50 mg/kg for 14 days. At 72 h after renal reperfusion, the kidney was harvested to assess inflammation and apoptosis. RESULTS: Pretreatment with allopurinol significantly improved renal functional and histological grade scores following I/R injury (p<0.05). Compared with Group B, the expression levels of caspase-3 and Bax were markedly reduced in Group C, meanwhile, whereas expression of bcl-2 was clearly increased (p<0.05). A newly described marker of inflammation, High Mobility Group Box 1(HMGB1), showed reduced expression in Group C (p<0.05). CONCLUSION: Pretreatment with allopurinol had a protective effect on kidney ischemia/reperfusion injury, which might be related to the inhibition of HMGB1 expression.

Allopurinol preconditioning attenuates renal ischemia/reperfusion injury by inhibiting HMGB1 expression in a rat model

ABSTRACT PURPOSE: To investigate the potential effects of pretreatment with allopurinol on renal ischemia/reperfusion injury (IRI) in a rat model. METHODS: Twenty four rats were subjected to right kidney uninephrectomy were randomly distributed into the following three groups (n=8): Group A (sham-operated group); Group B (ischemic group) with 30 min of renal ischemia after surgery; and Group C (allopurinol + ischemia group) pretreated with allopurinol at 50 mg/kg for 14 days. At 72 h after renal reperfusion, the kidney was harvested to assess inflammation and apoptosis. RESULTS: Pretreatment with allopurinol significantly improved renal functional and histological grade scores following I/R injury (p<0.05). Compared with Group B, the expression levels of caspase-3 and Bax were markedly reduced in Group C, meanwhile, whereas expression of bcl-2 was clearly increased (p<0.05). A newly described marker of inflammation, High Mobility Group Box 1(HMGB1), showed reduced expression in Group C (p<0.05). CONCLUSION: Pretreatment with allopurinol had a protective effect on kidney ischemia/reperfusion injury, which might be related to the inhibition of HMGB1 expression.

Ozone oxidative preconditioning protects the rat kidney from reperfusion injury: the role of nitric oxide.

BACKGROUND: Ischemia/reperfusion (I/R) injury, which is commonly seen in the field of renal surgery or transplantation, is a major cause of acute renal failure. Previous studies have shown that ozone oxidative preconditioning (OzoneOP) attenuated renal I/R injury. The objective of this study was to examine the hypothesis that protective effects of OzoneOP in renal I/R injury were associated with endogenous NO. MATERIALS AND METHODS: In a right-nephrectomized rat mode, anesthetized rats underwent 45 min of renal ischemia. OzoneOP (1 mg/kg) was administered before I/R injury. Rats were killed at 24, 48, and 72 h after I/R injury and blood samples and renal tissues were obtained. RESULTS: OzoneOP prevented the renal dysfunction induced by I/R and increased nitric oxide (NO) release and renal NO synthase (endothelial, eNOS, and inducible, iNOS) expression. In contrast, enhancement of endothelin-1 in the kidney after the reperfusion was markedly suppressed by OzoneOP. CONCLUSIONS: Our findings indicated that the protective effect of OzoneOP was closely related to the NO production following the increase in eNOS and iNOS expression. Ozone treatment may have important clinical implications, particularly in view of the minimizing renal damage before transplantation.

Similarities between ozone oxidative preconditioning and ischemic preconditioning in renal ischemia/reperfusion injury.

BACKGROUND: Many studies indicate that the production of reactive oxygen species (ROS) after renal ischemia/reperfusion (I/R) may initiate the cascade of cellular injury. It has been demonstrated that ozone oxidative preconditioning (OzoneOP) may prevent the damage induced by ROS and attenuate renal I/R injury. On the basis of those results, we postulated that OzoneOP was similar to the ischemic preconditioning (IP). The aim of our present work was to assess whether the combination of OzoneOP and IP provided synergistic protection. METHODS: Seven groups of rats were classified as follows: 1) sham-operated control; 2) I/R; 3) OzoneOP+I/R; 4) IP+I/R; 5) OzoneOP+IP+I/R; 6) O2+I/R; 7) sham-operated control+OzoneOP. Rats were sacrificed at 24 h after I/R injury. Serum and tissue were taken to determine urea nitrogen (BUN), creatinine (Cr), nitric oxide (NO), histological examination, and NO synthase (endothelial, eNOS and inducible, iNOS) expression. Malondialdehyde (MDA) content, glutathione (GSH) content, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity were determined in renal tissue. RESULTS: Renal dysfunction, histological damage, and renal oxidative stress were significantly improved by OzoneOP or IP alone. OzoneOP+IP could not further relieve severe renal damage. Either IP or OzoneOP treatment alone increased NO release and NO synthase (endothelial, eNOS and inducible, iNOS) expression. The combination of OzoneOP and IP could not further enhance NO levels and NOS expression. CONCLUSIONS: These findings indicate that both of the preconditioning settings shared similar mechanisms of protection in the parameters measured. However, OzoneOP combined with IP had no synergistic effect. IP and OzoneOP appeared to share a common mediator: NO. These findings suggested the potential role of OzoneOP against renal failure during surgery or transplantation.

Ozone oxidative preconditioning inhibits inflammation and apoptosis in a rat model of renal ischemia/reperfusion injury.

Ischemia/reperfusion injury, which is commonly seen in the field of renal surgery or transplantation, is a major cause of acute renal failure. Previous studies showed that ozone oxidative preconditioning (OzoneOP) attenuated renal ischemia/reperfusion injury. The objective of this study was to examine the role of the OzoneOP in modulating inflammation and apoptosis after renal ischemia/reperfusion injury. Rats were subjected to 45 min of renal ischemia, with or without treatment with OzoneOP (1 mg/kg). Renal function, inflammation and apoptosis were compared at 24 h after renal injury. OzoneOP improved the renal dysfunction and reduced inflammation and apoptosis after ischemia/reperfusion injury. In conclusion, OzoneOP has potent anti-apoptotic and anti-inflammatory properties. These findings may have major implications in the treatment of human ischemic acute renal failure.

Ischemic postconditioning inhibits apoptosis after renal ischemia/reperfusion injury in rat.

Ischemic postconditioning is a phenomenon that intermittent interruptions of blood flow in the early phase of reperfusion can protect organ from ischemia/reperfusion (I/R) injury. In the present study, we investigated whether the protective effect of ischemic postconditioning was associated with modulation of apoptosis after renal I/R injury. Rats were subjected to 45 min of renal ischemia, both with and without treatment with ischemic postconditioning. Serum urea nitrogen and creatinine levels, phosphorylation of Akt and ERK1/2 and apoptosis were compared after renal injury. Our data showed that ischemic postconditioning attenuated the renal dysfunction and cell apoptosis induced by I/R and increased phosphorylation of Akt and ERK1/2. The results indicated that ischemic postconditioning decreased apoptosis and improved renal function. This protective effect may be related with the levels of Akt and ERK1/2 activation. These findings may have major implications in the treatment of renal transplantation.