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Cardiomyocyte autophagy plays an important role in myocardial ischemia-reperfusion injury (MIRI). P300/CBP-associated factor (PCAF) was involved in the regulation of autophagy. However, the role of PCAF in MIRI is currently unknown. This study was to investigate whether downregulation of PCAF attenuate MIRI. The results showed that the expression of PCAF was significantly increased in MIRI and . Downregulation of PCAF not only inhibited autophagy and damage of H9c2 cells induced by hypoxia-reoxygenation, but also reduced autophagy and myocardial infarct size during myocardial ischemia-reperfusion in rats. In addition, downregulation of PCAF promoted activation of PI3K/Akt/mTOR signaling pathway in cardiomyocytes during hypoxia-reoxygenation. Wortmannin, a PI3K/Akt inhibitor, could abrogate the effects of downregulation of PCAF on cardiomyocytes autophagy. These results demonstrated that downregulation of PCAF alleviated MIRI by inhibiting cardiomyocyte autophagy through PI3K/Akt/mTOR signaling pathway. Thus, PCAF may be a potential target for prevention and treatment of MIRI.
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http://dx.doi.org/10.7150/ijms.44604 | DOI Listing |
EMBO Rep
August 2025
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 Wen Yuan Road, 210023, Nanjing, China.
PCAF (p300-associated factor), a major histone acetyltransferase, is involved in many metabolic and pathogenic diseases. Here, we reveal a novel function of PCAF in homologous recombination repair (HR). We demonstrate that RAD51, a core protein in HR repair, physically interacts with the acetyltransferase domain of PCAF and is acetylated at lysine 40.
View Article and Find Full Text PDFOncol Rep
April 2025
Division of Molecular Carcinogenesis, Chiba Cancer Center Research Institute, Chiba 260‑8717, Japan.
Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. Histone acetyltransferases (HATs), such as p300, CBP and PCAF, modulate numerous biological processes, including cellular proliferation and oncogenesis, through histone acetylation. In the present study, it was investigated whether the curcumin analogs such as pentagamavunon‑1 (PGV‑1) and chemoprevention curcumin analog‑1.
View Article and Find Full Text PDFRedox Biol
September 2024
Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address:
Lung cancer is a leading cause of cancer death worldwide, with high incidence and poor survival rates. Cold atmospheric plasma (CAP) technology has emerged as a promising therapeutic approach for cancer treatment, inducing oxidative stress in malignant tissues without causing thermal damage. However, the role of CAP in regulating lung cancer cell ferroptosis remains unclear.
View Article and Find Full Text PDFMechanisms of functional cross-talk between global transcriptional repression and efficient DNA damage repair during genotoxic stress are poorly known. In this study, using human AF9 as representative of Super Elongation Complex (SEC) components, we delineate detailed mechanisms of these processes. Mechanistically, we describe that Poly-Serine domain-mediated oligomerization is pre-requisite for AF9 YEATS domain-mediated TFIID interaction-dependent SEC recruitment at the promoter-proximal region for release of paused RNA polymerase II.
View Article and Find Full Text PDFBiomed Pharmacother
April 2024
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, China; Department of Dermatology, The Affiliated Hospital, Southwest Medical University, Luzhou, China. Electronic address:
Prostate cancer (PCa) is witnessing a concerning rise in incidence annually, with the androgen receptor (AR) emerging as a pivotal contributor to its growth and progression. Mounting evidence underscores the AR's ability to recruit cofactors, influencing downstream gene transcription and thereby fueling the proliferation and metastasis of PCa cells. Although, clinical strategies involving AR antagonists provide some relief, managing castration resistant prostate cancer (CRPC) remains a formidable challenge.
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