Breaking News
July 16, 2018 - Johnson & Johnson Announces Publication in The Lancet Highlighting Robust Immune Response to Janssen’s Mosaic-based Preventive Vaccine Regimen for HIV
July 16, 2018 - Do Racial and Gender Disparities Exist in Newer Glaucoma Treatments?
July 16, 2018 - Antibodies may predict transplant rejection risk
July 16, 2018 - New center sets out to stop disease before it starts | News Center
July 16, 2018 - UW-Madison researchers develop new method to track Parkinson’s damage in the heart
July 16, 2018 - New approach to cultivate hypoallergenic tomato and strawberry varieties
July 16, 2018 - Smoking associated with delayed shinbone healing
July 16, 2018 - Sheila Dolezal, ‘team player extraordinaire,’ wins 2018 Amy J. Blue Award | News Center
July 16, 2018 - Advanced Prostate Cancer Variant More Common Than Thought
July 16, 2018 - New ways to conquer sleep apnea compete for place in bedroom
July 16, 2018 - Renowned microbe hunter Stanley Falkow dies at 84 | News Center
July 15, 2018 - FDA Slaps Stronger Warnings on Potent Class of Antibiotics, Fluoroquinolones
July 15, 2018 - Don’t let depression keep you from exercising
July 15, 2018 - Student research symposium showcases curiosity and scholarship | News Center
July 15, 2018 - Heavy smokers have increased risk of heart rhythm disorder, shows study
July 15, 2018 - Parents who had severe trauma, stresses in childhood more likely to have kids with behavioral health problems
July 15, 2018 - At colloquium, a range of views on value of predictive algorithms | News Center
July 15, 2018 - Pittcon invites oral and poster presentations for 2019 Technical Program
July 15, 2018 - Virtual reality could offer psychotherapy for fear of heights, study shows
July 15, 2018 - Retooled vaccine raises hopes as a lower-cost treatment for Type 1 diabetes
July 15, 2018 - Kolon TissueGene To Start US Phase III Clinical Trial For Invossa
July 15, 2018 - Study finds prenatal marijuana use can affect infant size, behavior
July 15, 2018 - Howard Chang named HHMI investigator | News Center
July 15, 2018 - Study shows tailored mental health services improve wellbeing of emerging adults
July 15, 2018 - A bright future might help teens steer clear of violence
July 15, 2018 - Stanford Medicine magazine explores the art, science of listening and hearing | News Center
July 15, 2018 - New study tracks how the brain turns simple sensory inputs into meaningful categories
July 15, 2018 - Deadlier subtype of metastatic prostate cancer found to be common than previously thought
July 15, 2018 - UZH scientists identify enzyme that controls cell division
July 15, 2018 - Unhealthy Food Behaviors May Signal Eating Disorder in Teen
July 15, 2018 - Study raises doubts on a previous theory of Parkinson’s disease
July 15, 2018 - Grant awarded to study whether stem cells can treat urinary incontinence | News Center
July 15, 2018 - Imaging techniques may help assess immune system recovery in HIV patients
July 15, 2018 - Machine-learning may aid in diagnosis and treatment of mental health disorders
July 15, 2018 - ‘Skin Cancer, Take A Hike!’ program promotes sun safety and skin cancer awareness
July 15, 2018 - Blink Health announces lowest prices for generic prescriptions through Blue Eagle Health
July 15, 2018 - New drug strategy can alleviate multiple behavioral, cellular deficiencies in FXS mouse model
July 15, 2018 - Georgia State professor receives federal grant to study virus similar to Ebola virus
July 15, 2018 - Quitting Smoking? Even a Little Exercise Can Help You Stay Slim
July 15, 2018 - DBS treatment may slow the progression of Parkinson’s tremor in early-stage patients
July 15, 2018 - 5 Questions: Luby on virus with potential to cause global pandemic | News Center
July 15, 2018 - Corn loses its cancer-fighting phenolic acids when processed into cornflakes
July 15, 2018 - Study uncovers possible link between iron loading, alcohol intake and mortality
July 15, 2018 - Molecular insights of NagA enzyme could help combat TB
July 15, 2018 - The Facts on Tampons—and How to Use Them Safely
July 15, 2018 - Normalisation of ‘plus-size’ risks hidden danger of obesity, study finds
July 15, 2018 - $2.5 million award to support physician-scientist training | News Center
July 15, 2018 - Aeras announces publication of Phase 2 results of two TB vaccines
July 15, 2018 - Public to set research priorities in field of ethnic inequalities and severe mental illness
July 15, 2018 - Eisai and Biogen Announce Positive Topline Results of the Final Analysis for BAN2401 at 18 Months
July 15, 2018 - U.S. obesity rates rising again
July 15, 2018 - Millions could have incorrect statin, aspirin and blood pressure prescriptions | News Center
July 15, 2018 - Researchers identify factors associated with cell phone-related distracted driving in parents
July 15, 2018 - Bioethicists suggest ethical considerations for forensic use of genetic data
July 15, 2018 - Most clinical trial participants find benefits of sharing personal data outweigh risks, Stanford study finds | News Center
July 14, 2018 - Researchers solve protein puzzle that paves way for new cancer therapies
July 14, 2018 - Blood telomeres can help predict risk of disease worsening or death in COPD patients
July 14, 2018 - CDC: Nearly One-Third of Injury Deaths Occur at Home
July 14, 2018 - Injectable electronics offer powerful new tool in understanding how retinal cells work
July 14, 2018 - Human blood cells transformed into functional neurons | News Center
July 14, 2018 - Podcast: KHN’s ‘What the Health?’ ACA under fire. Again.
July 14, 2018 - Small device with motion sensors can predict older adults’ risk of falling
July 14, 2018 - Neurological Fallout From Ebola Infection Worse Than Thought
July 14, 2018 - Screening for impaired vision in older adults: New Canadian guideline
July 14, 2018 - Blood test for pregnant women can predict premature birth, Stanford-led study reports | News Center
July 14, 2018 - Study uncovers process that neutralizes tumor cells
July 14, 2018 - Four-protein biomarker blood test improves lung cancer risk assessment for smokers
July 14, 2018 - Researchers develop novel approach to bridge gap in cell-free systems
July 14, 2018 - Research reveals new gears in the circadian clock
July 14, 2018 - Researchers assess role of physician in preventing intimate partner violence perpetration
July 14, 2018 - Two diabetes medications don’t slow progression of type 2 diabetes in youth
July 14, 2018 - New clues to restoring fertility in women with disabling ovary disorder
July 14, 2018 - Compound in citrus oil could reduce dry mouth in head, neck cancer patients | News Center
July 14, 2018 - Streck ARM-D Kits detect more antibiotic resistance than comparable tests
July 14, 2018 - Study finds wide variations in follow-up imaging for women with non-metastatic breast cancer
July 14, 2018 - FDA expands its support for states to implement FSMA Produce Safety Rule
July 14, 2018 - CTI BioPharma Announces the Continuation without Modification of PAC203 Phase 2 Study of Pacritinib in Patients with Myelofibrosis Previously Treated with Ruxolitinib
July 14, 2018 - First-hand accounts of premature baby loss inspires new resource
July 14, 2018 - Study identifies cellular ‘death code’ | News Center
July 14, 2018 - Federal judge enters consent decree against Minnesota dairy farm for selling adulterated meat
Signaling pathway involving the Golgi apparatus identified in cells with Huntington’s disease

Signaling pathway involving the Golgi apparatus identified in cells with Huntington’s disease

image_pdfDownload PDFimage_print
Cells with Huntington’s disease lack the enzyme that creates cysteine and die in environments without it (Left). Cells treated with monensin have cysteine stores and are better prepared to survive in environments with little cysteine (Right). Credit: Juan Sbodio

Working with cells grown in the lab, Johns Hopkins researchers have identified a biochemical pathway that allows a structure within cells, called the Golgi apparatus, to combat stress caused by free radicals and oxidants. The research team showed that this pathway can be activated by a drug called monensin, which is commonly used as an antibiotic in animal feed.

The findings, they say, could help scientists develop new ways to protect cells against the type of oxidative stress linked to Huntington’s disease.

Details of the pathway, which involves the response from a series of proteins, are reported in the Jan. 9 issue of the Proceedings of the National Academy of Sciences.

“Normally, elevated oxidative stress is not good for cells, as it can compromise their natural protective responses,” says Bindu Paul, M.S., Ph.D., instructor of neuroscience at the Johns Hopkins University School of Medicine’s Solomon H. Snyder Department of Neuroscience. “We showed that we can enhance a pathway that protects the cells with a method that resembles vaccination. By giving a lower, less potent, dose of the stressor, you can boost the cell’s response so that it has a robust reaction to the real threat later on,” says Juan Sbodio, Ph.D., postdoctoral fellow at Johns Hopkins University School of Medicine’s Solomon H. Snyder Department of Neuroscience.

The Golgi is best known for its role as the shipping and sorting center of the cell, shuttling proteins to their proper locations. However, the ribbon-like structure is also one of the first responders to cellular stress, and it helps to protect the cell by producing cysteine, a basic building block of the proteins that make up our bodies, including the body’s natural antioxidant glutathione.

When a cell is exposed to cysteine deprivation and oxidative stress, the cell sends out the alarm to produce more cysteine to create glutathione, which combats oxidative stress by binding to and neutralizing oxidating agents. The researchers knew that a similar process is initiated by the Golgi when exposed to monensin to induce Golgi stress and wanted to explore this response further.

To better understand the effects of the drug, the scientists bathed cells in low doses of monensin, which, at high doses, is known to break apart Golgi. The researchers found that after the treatment, the proteins PERK, ATF4 and cystathionine ?-lyase (CSE)—the protein that is activated to create cysteine—appeared in elevated levels within the cell compared to nontreated cells. Previous research has linked low CSE production to Huntington’s disease. Because of this, researchers believe that neurons with Huntington’s disease cannot counteract dangerous free radicals or oxidants and are at risk of dying from stress.

The researchers wanted to find if there was a way to increase cysteine production in afflicted cells to protect them. The researchers gave lab-grown mouse cells that mimicked human Huntington’s disease a small dose of monensin and depleted cysteine in their nutrient bath.

The cells treated with monensin grew normally for 7-9 days during the experiment, while those not treated with monensin withered away, the team reports.

“We think that the monensin treatment built up the cell’s reserve of CSE and cysteine, protecting the cells against low cysteine levels,” says Paul.

The researchers also found that this stress response pathway also kick starts another pathway that creates hydrogen sulfide, a gas and key regulator for many important cellular processes.

In the future, the researchers hope to further study the pathway’s role in overall cellular health.


Explore further:
New evidence: How amino acid cysteine combats Huntington’s disease

More information:
Juan I. Sbodio et al, Golgi stress response reprograms cysteine metabolism to confer cytoprotection in Huntington’s disease, Proceedings of the National Academy of Sciences (2018). DOI: 10.1073/pnas.1717877115

Journal reference:
Proceedings of the National Academy of Sciences

Provided by:
Johns Hopkins University School of Medicine

Tagged with:

About author

Related Articles