Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

27 November 2018 : Animal Research  

P27 Protects Cardiomyocytes from Sepsis via Activation of Autophagy and Inhibition of Apoptosis

Xianyuan Zhao1ABF, Hong Qi2DFG, Jiamin Zhou3ABG, Shuqi Xu4CDE, Yuan Gao5CDE*

DOI: 10.12659/MSM.912750

Med Sci Monit 2018; 24: ANS8565-8576

Abstract

BACKGROUND: It has been reported that p27Kip1 plays an important role not only in the inhibition of cyclin-dependent kinases but also in the regulation of autophagy under various metabolically related stress conditions, including glucose deprivation and endoplasmic reticulum stress. However, its effect on lipopolysaccharide (LPS)-induced cardiomyocyte stress in vitro remains unclear. Here, we measured the increased expression of LC3-II and visualized autophagosomes in vitro by immunofluorescent assays after treatment with a p27 fusion protein.

MATERIAL AND METHODS: Cardiomyocyte contractile properties were assessed by measuring cell shortening and re-lengthening. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Western blot, colorectal ligation puncture (CLP) surgery, silencing of Atg5 expression by small interfering RNA (siRNA), and immunofluorescent assays were also performed in this study.

RESULTS: After exogenous delivery of the p27 fusion protein and overexpression of p27 in LPS-induced cardiomyocytes, we found lower expressions of caspase-3 and caspase-8 and reduced positive TUNEL staining. Improved cardiomyocyte mechanical functions and reduced apoptosis were diminished after treatment with various autophagy inhibitors. Intravenous injections of p27-expressing adeno-associated virus serotype 9 (AAV9) vectors resulted in cardiac specific overexpression of p27, and echocardiography was used to assess cardiac function and structure in sepsis rat models. We observed improved cardiac function and reversed adverse ventricular remolding after the introduction of AAV9 vectors. Meanwhile, apoptosis was reduced, and expression of LC3-II was elevated in septic rat models treated with AAV9 vectors compared to controls.

CONCLUSIONS: The study data demonstrated that the overexpression of p27 protects cardiomyocytes from sepsis-induced cardiac depression via the activation of autophagy and inhibition of apoptosis.

Keywords: Asepsis, Sepsis, Systemic Inflammatory Response Syndrome

Add Comment 0 Comments

Editorial

01 June 2024 : Editorial  

Editorial: Concerns as Highly Pathogenic Avian Influenza (HPAI) Virus of the H5N1 Subtype is Identified in Dairy Cows and Other Mammals

Dinah V. Parums

DOI: 10.12659/MSM.945315

Med Sci Monit 2024; 30:e945315

0:00

In Press

Clinical Research  

Morphological and Dimensional Analysis of the Nasopalatine Canal: Insights from Cone-Beam Computed Tomograp...

Med Sci Monit In Press; DOI: 10.12659/MSM.944424  

Clinical Research  

Hemorrhagic Cysts in the Pancreas: Risk Factors, Treatment, and Outcomes – Insights from a Single-Center Study

Med Sci Monit In Press; DOI: 10.12659/MSM.941955  

Clinical Research  

Perioperative Administration of Tranexamic Acid and Low Molecular Weight Heparin for Enhanced Blood Managem...

Med Sci Monit In Press; DOI: 10.12659/MSM.944063  

Database Analysis  

Comprehensive Analysis of Sphingolipid Metabolism-Related Genes in Osteoarthritic Diagnosis and Synovial Im...

Med Sci Monit In Press; DOI: 10.12659/MSM.943369  

Most Viewed Current Articles

14 Dec 2022 : Clinical Research   1,441,389

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

17 Jan 2024 : Review article   1,376,349

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

16 May 2023 : Clinical Research   690,122

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

01 Jan 2022 : Editorial   50,127

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750