BACKGROUNDS: RNA-binding protein QKI is abundantly expressed in the brain and heart. The role of QKI in the nervous system has been well characterized, but its function in cardiac muscle is still poorly understood. The present study was to investigate the role of QKI in ischemia/reperfusion-induced apoptosis in cardiomyocytes. METHODS: A simulated ischemia/reperfusion model was established in neonatal cardiomyocytes and adult rat heart. After QKI5 or QKI6 was expressed by adenovirus and QKI was knocked down QKI by RNAi in the cardiomyocytes, RT-PCR, western blot and immunofluorescence staining were applied to detect gene expression alterations. Apoptosis was evaluated by PARP degradation, DNA fragmentation (DNA laddering) and flow cytometry. RESULTS: Our study demonstrated that both QKI5 and QKI6 were present in cardiomyocytes, while QKI5 expression was greatly inhibited by simulated ischemia/reperfusion. Knocking down endogenous QKI by RNAi enhanced cell susceptibility to apoptosis, whereas overexpression of either QKI5 or QKI6 suppressed IR-induced apoptosis substantially. The pro-apoptotic transcription factor FoxO1, a potential QKI target, was induced by ischemia/reperfusion at both total amount and nuclear distribution. Accordingly, FOXO1 downstream target genes were negatively affected by the presence of QKI with IR treatment. CONCLUSION: In summary, our study supports that both QKI-5 and 6 are anti-apoptotic proteins in cardiomyocytes, favoring cardiac survival via antagonizing the elevation of some pro-apoptotic factors in cardiac injury.
BACKGROUNDS: RNA-binding protein QKI is abundantly expressed in the brain and heart. The role of QKI in the nervous system has been well characterized, but its function in cardiac muscle is still poorly understood. The present study was to investigate the role of QKI in ischemia/reperfusion-induced apoptosis in cardiomyocytes. METHODS: A simulated ischemia/reperfusion model was established in neonatal cardiomyocytes and adult rat heart. After QKI5 or QKI6 was expressed by adenovirus and QKI was knocked down QKI by RNAi in the cardiomyocytes, RT-PCR, western blot and immunofluorescence staining were applied to detect gene expression alterations. Apoptosis was evaluated by PARP degradation, DNA fragmentation (DNA laddering) and flow cytometry. RESULTS: Our study demonstrated that both QKI5 and QKI6 were present in cardiomyocytes, while QKI5 expression was greatly inhibited by simulated ischemia/reperfusion. Knocking down endogenous QKI by RNAi enhanced cell susceptibility to apoptosis, whereas overexpression of either QKI5 or QKI6 suppressed IR-induced apoptosis substantially. The pro-apoptotic transcription factor FoxO1, a potential QKI target, was induced by ischemia/reperfusion at both total amount and nuclear distribution. Accordingly, FOXO1 downstream target genes were negatively affected by the presence of QKI with IR treatment. CONCLUSION: In summary, our study supports that both QKI-5 and 6 are anti-apoptotic proteins in cardiomyocytes, favoring cardiac survival via antagonizing the elevation of some pro-apoptotic factors in cardiac injury.
Authors: Carmen C Sucharov; Juliana Sucharov; Anis Karimpour-Fard; Karin Nunley; Brian L Stauffer; Shelley D Miyamoto Journal: J Card Fail Date: 2014-10-05 Impact factor: 5.712
Authors: Matteo D'Antonio; Jennifer P Nguyen; Timothy D Arthur; Hiroko Matsui; Margaret K R Donovan; Agnieszka D'Antonio-Chronowska; Kelly A Frazer Journal: PLoS Comput Biol Date: 2022-02-28 Impact factor: 4.475