Nuclear AMPK regulated CARM1 stabilization impacts autophagy in aged heart

Li, Chen; Yu, Lu; Xue, Han; Yang, Zuozhang; Yin, Yulong; Zhang, Bo; Chen, Mai; Ma, Heng

doi:10.1016/j.bbrc.2017.03.053

Cited by 40 publications

(35 citation statements)

References 25 publications

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“…In addition, it has been discovered in aged hearts that AMPK down-regulation gives rise to nuclear CARM1 deficiency mediated partly by SKP2, leading to autophagy disorders. In the nucleus, AMPK regulates CARM1 stabilization that controls autophagy of hearts [33]. These findings correlate with our hypothesis and results.…”

Section: Discussionsupporting

confidence: 82%

SKP2 Promotes Hepatocellular Carcinoma Progression Through Nuclear AMPK-SKP2-CARM1 Signaling Transcriptionally Regulating Nutrient-Deprived Autophagy Induction

Wei

Yan

et al. 2018

Cell Physiol Biochem

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Background/Aims: SKP2 overexpression has been associated with poor prognosis in numerous cancers. The mechanisms of autophagy in the tumor pathogenesis have been a research focus recently. How the SKP2 involved in autophagy expresses oncogenic characteristics, especially in HCC, are largely unclear. Methods: The expression of SKP2 was detected by qPCR, Western blot, Immunohistochemical (IHC) and Immunofluorescence (IF) techniques. SKP2 was knocked down or overexpressed by lentivirus transfection in HCC cells. Functional assays such as CCK8 assays, transwell migration and invasion assays, and colony formation assays were performed to determine the role of SKP2 in HCC. Furthermore, autophagy was induced by glucose deprivation in HCC cells followed by monitoring of the levels and distributions of SKP2, CARM1 and AMPK. Results: Our data showed that SKP2 levels were significantly increased in HCC cell lines and HCC tissues rather than corresponding normal liver tissues, and augmented SKP2 levels were statistically correlated with tumor grade, size and metastases. By up-regulation or down-regulation of SKP2 in HCC cells, we confirmed that SKP2 encourages proliferation, migration, invasion, and colony formation. We then found that SKP2 was inhibited, CARM1 increased and AMPKα2 became activated in the nucleus under glucose deprivation induced autophagy. Moreover, we discovered that SKP2 was repressing CARM1 in the nucleus under nutrient-sufficient conditions in HCC. Conclusions: We show that SKP2 promotes HCC progression and its nuclear functions of autophagy induction with CARM1 and AMPK, which may provide a potential target for HCC therapy.

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Section: Discussionsupporting

confidence: 82%

SKP2 Promotes Hepatocellular Carcinoma Progression Through Nuclear AMPK-SKP2-CARM1 Signaling Transcriptionally Regulating Nutrient-Deprived Autophagy Induction

Wei

Yan

et al. 2018

Cell Physiol Biochem

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“…In addition, PRMT5 directly methylates GATA4 transcription factor, and inhibits phenylephrine-induced cardiomyocyte hypertrophy in neonatal rat ventricular myocytes ( Chen et al., 2014 ). PRMT4 has been shown to regulate aging-related autophagy in mouse heart ( Li et al., 2017 ). Interestingly, cardiac PRMT1 expression is increased in patients with coronary artery disease and in rats with isoproterenol-induced heart failure ( Chen et al., 2006 , Li et al., 2012 ), suggesting the importance of PRMT1 in the heart.…”

Section: Introductionmentioning

confidence: 99%

PRMT1 Deficiency in Mouse Juvenile Heart Induces Dilated Cardiomyopathy and Reveals Cryptic Alternative Splicing Products

Murata

Hashimoto

et al. 2018

iScience

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SummaryProtein arginine methyltransferase 1 (PRMT1) catalyzes the asymmetric dimethylation of arginine residues in proteins and methylation of various RNA-binding proteins and is associated with alternative splicing in vitro. Although PRMT1 has essential in vivo roles in embryonic development, CNS development, and skeletal muscle regeneration, the functional importance of PRMT1 in the heart remains to be elucidated. Here, we report that juvenile cardiomyocyte-specific PRMT1-deficient mice develop severe dilated cardiomyopathy and exhibit aberrant cardiac alternative splicing. Furthermore, we identified previously undefined cardiac alternative splicing isoforms of four genes (Asb2, Fbxo40, Nrap, and Eif4a2) in PRMT1-cKO mice and revealed that eIF4A2 protein isoforms translated from alternatively spliced mRNA were differentially ubiquitinated and degraded by the ubiquitin-proteasome system. These findings highlight the essential roles of PRMT1 in cardiac homeostasis and alternative splicing regulation.

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“…Corpus cavernous tissues were cut up with a sharp blade to less than 0.5 mm 3 . Nucleoproteins and cytoplasmic proteins were extracted by the NE‐PER Nuclear and Cytoplasmic Extraction Reagents Kit (Thermo) . The tissues were homogenized by a magnetic bead homogenizer (Bead Ruptor 24, OMNI) and centrifuged for 30 minutes (4°C, 12 000 g ).…”

Section: Methodsmentioning

confidence: 99%

Simvastatin alleviated diabetes mellitus‐induced erectile dysfunction in rats by enhancing AMPK pathway‐induced autophagy

Fan

Shan

et al. 2020

Andrology

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Background: Diabetes mellitus-induced erectile dysfunction is a common diabetic complication, and new therapeutics and the pathogenesis of diabetes mellitus-induced erectile dysfunction need to be investigated. Objectives:The aim was to investigate the pathogenesis of diabetes mellitus-induced erectile dysfunction and the pharmacological mechanism of simvastatin treatment in diabetes mellitus-induced erectile dysfunction model rats. Materials and methods:A total of 86 male Sprague Dawley rats aged 8 weeks old were used in this study. The rats were divided into three groups: control (normal), diabetes mellitus-induced erectile dysfunction (streptozotocin-injected), and diabetes mellitus-induced erectile dysfunction + simvastatin (sim). Each group was subdivided into two subgroups for in vitro and in vivo analyses. A bioinformatics method was used to detect differences in gene expression in the corpus cavernosum between normal and diabetes mellitus-induced erectile dysfunction rats. Erectile function was measured by a cavernous nerve electrostimulation test. Corpus cavernosum fibrosis was assessed by Masson staining and Western blotting. Immunofluorescence and Western blotting were performed to explore the differential expression of autophagy-related genes and the AMPK-SKP2-CARM1 pathway genes in rat cavernous smooth muscle cells and the corpus cavernosum. The autophagosomes of the corpus cavernosum tissue were observed by transmission electron microscopy. Results:Autophagy-related genes and pathways (the AMPK and FoxO pathway) were identified by bioinformatics analysis and confirmed at the protein level. Simvastatin, an AMPK agonist, was used to treat diabetes mellitus-induced erectile dysfunction rats for 8 weeks, demonstrating that erectile function was improved for 80.5% (P < .05) of rats. Corpus cavernosum fibrosis was alleviated (P < .05), and autophagy was further enhanced (P < .05); these results might be partially caused by AMPK-SKP2-CARM1 pathway activation (P < .05). Discussion and conclusion:Simvastatin could enhance protective autophagy by activating the AMPK-SKP2-CARM1 pathway to improve erectile function in diabetes mellitus-induced erectile dysfunction rats. | 781DING et al.

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Nuclear AMPK regulated CARM1 stabilization impacts autophagy in aged heart

Cited by 40 publications

References 25 publications

SKP2 Promotes Hepatocellular Carcinoma Progression Through Nuclear AMPK-SKP2-CARM1 Signaling Transcriptionally Regulating Nutrient-Deprived Autophagy Induction

SKP2 Promotes Hepatocellular Carcinoma Progression Through Nuclear AMPK-SKP2-CARM1 Signaling Transcriptionally Regulating Nutrient-Deprived Autophagy Induction

PRMT1 Deficiency in Mouse Juvenile Heart Induces Dilated Cardiomyopathy and Reveals Cryptic Alternative Splicing Products

Simvastatin alleviated diabetes mellitus‐induced erectile dysfunction in rats by enhancing AMPK pathway‐induced autophagy

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