JNK inhibition alleviates oxidative DNA damage, germ cell apoptosis, and mitochondrial dysfunction in testicular ischemia reperfusion injury
| Autor: | Nora Al-Kandari, May Al-Maghrebi, Fatemah Fadel, Farah Al-Saleh, Farah Khashab |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine MAP Kinase Kinase 4 DNA damage Biophysics Apoptosis Caspase 3 Mitochondrion medicine.disease_cause Protein oxidation Testicular Diseases Biochemistry Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Testis Survivin medicine Animals Spermatogenesis Anthracenes Chemistry General Medicine medicine.disease Molecular biology Mitochondria Rats Germ Cells 030104 developmental biology Reperfusion Injury 030220 oncology & carcinogenesis Reperfusion injury Oxidative stress DNA Damage |
| Zdroj: | Acta Biochimica et Biophysica Sinica. 52:891-900 |
| ISSN: | 1672-9145 |
| DOI: | 10.1093/abbs/gmaa074 |
| Popis: | The aim of this study is to determine whether the c-Jun N-terminal kinase (JNK) signaling is a regulator of oxidative DNA damage, germ cell apoptosis (GCA), and mitochondrial dysfunction during testicular ischemia reperfusion injury (tIRI) using the JNK inhibitor SP600125. Male Sprague Dawley rats (n = 36) were equally divided into three groups: sham, tIRI only, and tIRI + SP600125 (15 mg/kg). Testicular ischemia was induced for 1 h followed by 4 h of reperfusion prior to animal sacrifice. Spermatogenesis was evaluated by light microscopy, while expression of oxidative stress and GCA-related mRNAs and proteins were evaluated by real-time polymerase chain reaction and colorimetric assays, respectively. Expressions of JNK, p53, and survivin were detected by immunofluorescence (IF) staining. Indicators of mitochondrial dysfunction were examined by western blot analysis and colorimetric assay. In comparison to sham, the tIRI testes showed a significant increase in lipid and protein oxidation products. Oxidative DNA damage was reflected by a significant increase in the number of DNA strand breaks, increased concentration of 8-OHdG, and elevated poly (ADP-ribose) polymerase activity. Spermatogenic damage was associated with the activation of caspase 3 and elevated Bax to Bcl2 ratio. This was also accompanied by a significantly heightened IF expression of the phosphorylated forms of JNK and p53 paralled with the suppression of survivin. Mitochondrial dysfunction was reflected by NAD+ depletion, overexpression of uncoupling protein 2, and increased level of cytochrome c. Such tIRI-induced modulations were all attenuated by SP600125 treatment prior to reperfusion. In conclusion, JNK signaling regulates oxidative DNA damage, GCA, and mitochondrial dysfunction through activation of p53 and suppression of survivin during tIRI. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|