Topics

A Novel Role of Prolidase in Cocaine-Mediated Breach in the Barrier of Brain Microvascular Endothelial Cells.

07:00 EST 22nd February 2019 | BioPortfolio

Summary of "A Novel Role of Prolidase in Cocaine-Mediated Breach in the Barrier of Brain Microvascular Endothelial Cells."

Cocaine use is associated with breach in the blood brain barrier (BBB) and increased HIV-1 neuro-invasion. We show that the cellular enzyme "Prolidase" plays a key role in cocaine-induced disruption of the BBB. We established a barrier model to mimic the BBB by culturing human brain microvascular endothelial cells (HBMECs) in transwell inserts. In this model, cocaine treatment enhanced permeability of FITC-dextran suggesting a breach in the barrier. Interestingly, cocaine treatment increased the activity of matrix metallo-proteinases that initiate degradation of the BBB-associated collagen. Cocaine exposure also induced prolidase expression and activity in HBMECs. Prolidase catalyzes the final and rate-limiting step of collagen degradation during BBB remodeling. Knock-down of prolidase abrogated cocaine-mediated increased permeability suggesting a direct role of prolidase in BBB breach. To decipher the mechanism by which cocaine regulates prolidase, we probed the inducible nitric oxide synthase (iNOS) mediated phosphorylation of prolidase since mRNA levels of the protein were not altered upon cocaine treatment. We observed increased iNOS expression concurrent with increased prolidase phosphorylation in cocaine treated cells. Subsequently, inhibition of iNOS decreased prolidase phosphorylation and reduced cocaine-mediated permeability. Finally, cocaine treatment increased transmigration of monocytic cells through the HBMEC barrier. Knock-down of prolidase reduced cocaine-mediated monocyte transmigration, establishing a key role of prolidase in cocaine-induced breach in endothelial cell barrier.

Affiliation

Journal Details

This article was published in the following journal.

Name: Scientific reports
ISSN: 2045-2322
Pages: 2567

Links

DeepDyve research library

PubMed Articles [21221 Associated PubMed Articles listed on BioPortfolio]

A novel role for E2F3b in regulating cocaine action in the prefrontal cortex.

Drug abuse is a multifaceted disorder that involves maladaptive decision making. Long-lasting changes in the addicted brain are mediated by a complex circuit of brain reward regions. The prefrontal co...

Tryptophan carbon dots and their ability to cross the blood-brain barrier.

Drug traversal across the blood-brain barrier has come under increasing scrutiny recently, particularly concerning the treatment of sicknesses, such as brain cancer and Alzheimer's disease. Most thera...

Nociceptin Receptors Upregulated in Cocaine Use Disorder: A Positron Emission Tomography Imaging Study Using CNOP-1A.

Nociceptin/orphanin FQ (N/OFQ) is an antistress neuropeptide transmitter in the brain that counteracts corticotropin-releasing factor (CRF)-mediated stress and anxiety symptoms during drug and alcohol...

P53 knockout mice are protected from cocaine-induced kindling behaviors via inhibiting mitochondrial oxidative burdens, mitochondrial dysfunction, and proapoptotic changes.

Previously we demonstrated that p53 mediates dopaminergic neurotoxicity via inducing mitochondrial burdens and proapoptotsis. However, little is known about the role of p53 in the excitotoxicity induc...

Blood-brain barrier pericytes as a target for HIV-1 infection.

Pericytes are multifunctional cells wrapped around endothelial cells via cytoplasmic processes that extend along the abluminal surface of the endothelium. The interactions between endothelial cells an...

Clinical Trials [8281 Associated Clinical Trials listed on BioPortfolio]

Oxytocin in Cocaine Dependence

Stress is likely involved in relapse to cocaine use. This project will investigate the role oxytocin may play in the stress response in cocaine-dependent men and women and examine how oxyt...

Prolidase Enzyme Activity in Stroke Patients

Stroke is a major cerebrovascular disease that causes significant burdens for human health and life, including high morbidity, mortality, and disability. Prolidase enzyme activity was foun...

Brain Imaging: Cocaine Effects & Medication Development - 5

The purpose of this study is to define temporal profile of brain activation (rCBF) using Xenon-SPECT and O 15-PET.

Deep Brain Stimulation of the Sub-Thalamic Nucleus to Treat Severe and Treatment-resistant Cocaine Addiction.

Cocaine addiction is a chronic condition with severe cardiac, neurologic, psychiatric and social complications. Cocaine is the second most consumed illicit drug in France. Its prevalence h...

Metabolic Effects of Cocaine

The goal of this this study is to elucidate the role of the HPA axis in the pathophysiology of cocaine dependence

Medical and Biotech [MESH] Definitions

The barrier between the perineurium of PERIPHERAL NERVES and the endothelium (ENDOTHELIUM, VASCULAR) of endoneurial CAPILLARIES. The perineurium acts as a diffusion barrier, but ion permeability at the blood-nerve barrier is still higher than at the BLOOD-BRAIN BARRIER.

Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.

Rare autosomal recessive disorder of metabolism due to mutations in the prolidase gene. It is characterized by recurrent lower extremity skin ulcers, recurrent infections, and FACIES, often with mental retardation.

The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement.

An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.

Quick Search


DeepDyve research library

Relevant Topics

Neurology - Central Nervous System (CNS)
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinson's Disease Sleep Disorders Neurology is the branch of me...

Enzymes
Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical re...


Searches Linking to this Article