AI Article Synopsis

  • The ductus arteriosus (DA) constricts in response to rising oxygen levels at birth, and this process is influenced by reactive oxygen species (ROS) produced by the mitochondrial electron transport chain (ETC) within smooth muscle cells of the DA.
  • Research was conducted using electron leak suppressors (S1QEL and S3QEL) to determine their effects on DA constriction and ROS generation, with findings showing that S1QEL effectively reversed oxygen-induced constriction without affecting other constriction pathways.
  • The study concluded that the oxygen sensing in the DA primarily depends on electron leak at site I of the ETC, indicating that S1QEL could be a potential therapeutic option to keep the DA patent (open

Article Abstract

Background As partial pressure of oxygen (pO) rises with the first breath, the ductus arteriosus (DA) constricts, diverting blood flow to the pulmonary circulation. The DA's O sensor resides within smooth muscle cells. The DA smooth muscle cells' mitochondrial electron transport chain (ETC) produces reactive oxygen species (ROS) in proportion to oxygen tension, causing vasoconstriction by regulating redox-sensitive ion channels and enzymes. To identify which ETC complex contributes most to DA O sensing and determine whether ROS mediate O sensing independent of metabolism, we used electron leak suppressors, S1QEL (suppressor of site I electron leak) and S3QEL (suppressor of site III electron leak), which decrease ROS production by inhibiting electron leak from quinone sites I and III, respectively. Methods and Results The effects of S1QEL, S3QEL, and ETC inhibitors (rotenone and antimycin A) on DA tone, mitochondrial metabolism, O-induced changes in intracellular calcium, and ROS were studied in rabbit DA rings, and human and rabbit DA smooth muscle cells. S1QEL's effects on DA patency were assessed in rabbit kits, using micro computed tomography. In DA rings, S1QEL, but not S3QEL, reversed O-induced constriction (=0.0034) without reducing phenylephrine-induced constriction. S1QEL did not inhibit mitochondrial metabolism or ETC-I activity. In human DA smooth muscle cells, S1QEL and rotenone inhibited O-induced increases in intracellular calcium (=0.02 and 0.001, respectively), a surrogate for DA constriction. S1QEL inhibited O-induced ROS generation (=0.02). In vivo, S1QEL prevented O-induced DA closure (<0.0001). Conclusions S1QEL, but not S3QEL, inhibited O-induced rises in ROS and DA constriction ex vivo and in vivo. DA O sensing relies on pO-dependent changes in electron leak at site I in ETC-I, independent of metabolism. S1QEL offers a therapeutic means to maintain DA patency.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10356098PMC
http://dx.doi.org/10.1161/JAHA.122.029131DOI Listing

Publication Analysis

Top Keywords

electron leak
20
smooth muscle
16
muscle cells
12
mitochondrial electron
8
electron transport
8
transport chain
8
ductus arteriosus
8
suppressor site
8
s1qel s3qel
8
mitochondrial metabolism
8

Similar Publications

Objectives: To examine the effect of the NAD precursor, nicotinic acid (NA), for improving skeletal muscle status in sedentary older people.

Methods: In a double-blind, randomised, placebo-controlled design, 18 sedentary yet otherwise healthy older (65-75 y) males were assigned to 2-weeks of NA (acipimox; 250 mg × 3 daily, n=8) or placebo (PLA, n=10) supplementation. At baseline, and after week 1 and week 2 of supplementation, a battery of functional, metabolic, and molecular readouts were measured.

View Article and Find Full Text PDF

Effects of cellulose nanofibrils on the mechanical and thermal properties of phase change foams based on polyethylene glycol/cellulose nanofibrils/waterborne polyurethane.

Int J Biol Macromol

December 2024

Key Lab of Wood Science and Technology of State Forestry Administration, Research Institute of Wood Industry, Chinese Academy of Forestry, Beijing 100091, PR China. Electronic address:

Incorporating phase change materials (PCM) into three-dimensional porous network structures could effectively address the leakage problem. In this study, by investigating the effects of different cellulose nanofibrils (CNF) contents on the mechanical and thermal properties of polyethylene glycol (PEG)/CNF/waterborne polyurethane (WPU) phase change foams, a series of leak-proof, lightweight, and stable PEG/CNF/WPU phase change foams were synthesized. Utilizing CNFs as porous support materials could effectively mitigate the leakage of PCMs.

View Article and Find Full Text PDF

By employing a graded-interfaces model based on a generalized formalism for interface-roughness (IFR) scattering that was modified for mid-infrared emitting quantum cascade lasers (QCLs), we have accurately reproduced the electro-optical characteristics of published record-performance 4.9 µm- and 8.3 µm-emitting QCLs.

View Article and Find Full Text PDF

Embryos undergo pre-gastrulation cleavage cycles to generate a critical cell mass before transitioning to morphogenesis. The molecular underpinnings of this transition have traditionally centered on zygotic chromatin remodeling and genome activation, as their repression can prevent downstream processes of differentiation and organogenesis. Despite precedents that oxygen depletion can similarly suspend development in early embryos, hinting at a pivotal role for oxygen metabolism in this transition, whether there is a chemical switch that licenses the onset of morphogenesis remains unknown.

View Article and Find Full Text PDF

Mitochondria are considered one of the main sites of reactive oxygen species (ROS) production in the eukaryotic cells. For this reason, mitochondrial dysfunction associated with increased ROS production underlies various pathological conditions as well as promotes aging. Chronically increased rates of ROS production contribute to oxidative damage to macromolecules, i.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: