Breaking News
September 20, 2018 - AbbVie Announces Patient-Reported Outcomes Data from Three Pivotal Phase 3 Studies of Risankizumab, Showing Significant Improvements in Health-Related Quality of Life for Patients with Psoriasis
September 20, 2018 - Characterization of pregnancy microbiome reveals variations in bacterial diversity
September 20, 2018 - New guidance for treatment of bone loss in hematologic stem cell transplant Recipients
September 20, 2018 - Experts to present research on prevention, management of dysphagia at international conference
September 20, 2018 - New study focuses on two-way gene switches controlling gene activity
September 20, 2018 - Zika virus could become a weapon against brain cancer
September 20, 2018 - Home-based video game exercises can reduce chronic low back pain in older people, study finds
September 20, 2018 - Investigators find that bile acids reduce cocaine reward
September 20, 2018 - Cannabinoid drugs reduce perceived unpleasantness of painful stimuli and increase tolerance
September 20, 2018 - Health care companies’ data could enable more accurate flu season forecasts
September 20, 2018 - Geroscience takes center stage in Journal of the American Medical Association
September 20, 2018 - Ambient Particulate Matter Linked to Emergency Asthma Care
September 20, 2018 - Patient satisfaction with plastic surgery—it’s the surgeon, not the practice
September 20, 2018 - Medicine is a team sport – and that’s exactly how it should be
September 20, 2018 - Logos Biosystems releases new electrophoretic tissue clearing system with twice the features in half the space
September 20, 2018 - Novel micro-platform reveals never-before-seen behaviors of cancer cells
September 20, 2018 - PAREXEL partners with Datavant to enhance clinical study design and generate real-world evidence
September 20, 2018 - Robert Koch Institute publishes new data on allergies, mental health problems, and accident injuries
September 20, 2018 - Study finds higher readmission rates in for-profit hospitals
September 20, 2018 - Encouraging youth to do strength-based exercises could help tackle child obesity
September 20, 2018 - Sleep apnea, congenital heart disease in hospitalized infants strongly associated with death
September 20, 2018 - Researchers find way to map mysterious content of non-coding RNA
September 20, 2018 - Air Pollutants Reach Placenta, Might Harm Fetus: Study
September 20, 2018 - Sleep apnea, congenital heart disease may be deadly mix for hospitalized infants
September 20, 2018 - My relative has cancer, should I worry? Encouraging cascade genetic testing
September 20, 2018 - Investigators determine specific treatable traits that can predict future asthma attacks
September 20, 2018 - More doctor visits can lower risk of suicide attempts in fibromyalgia patients
September 20, 2018 - Computer avatars play role in diagnosis of dementia
September 20, 2018 - Addition of CTLA4 targeted therapy to PD-1 targeted therapy may benefit patients with ovarian cancer
September 20, 2018 - ASPREE trial explores whether low dose aspirin can prolong good health in elderly people
September 20, 2018 - ATS publishes new guideline focused on weight loss strategies for sleep apnea patients
September 20, 2018 - The Current issue of “The view from here” is concerned with Drug Delivery
September 19, 2018 - Sleep apnea could favour tumor growth at young ages
September 19, 2018 - Stealth vaping fad hidden from parents, teachers
September 19, 2018 - Witnessing school violence linked to later risk of psycho-social and academic impairment
September 19, 2018 - Common household cleaners could make children overweight by changing gut microbiota
September 19, 2018 - Salk research in yeast leads to serendipitous finding about hypomyelinating leukodystrophy
September 19, 2018 - Study: Overweight or obese women may have increased risk of urinary incontinence
September 19, 2018 - Study shows how cellular waste disposal processes also promote inflammation
September 19, 2018 - New multidisciplinary microsurgery microscope, PROVIDO, introduced by Leica
September 19, 2018 - Phase 2b STORM Data Evaluating Selinexor in Patients with Penta-Refractory Multiple Myeloma Presented at the Society of Hematologic Oncology 2018 Annual Meeting
September 19, 2018 - Decisions recruiting gut feelings seen as reflection of true self, more assuredly held, study says
September 19, 2018 - How AI can improve end-of-life care
September 19, 2018 - UNIST and Ulsan initiate research collaboration to develop human organs-on-chips
September 19, 2018 - Study highlights key role of migrating shoals of fish in sustaining deep-ocean microorganisms
September 19, 2018 - Disagreeable individuals can benefit most from behaving more compassionately, finds study
September 19, 2018 - Janssen Submits New Drug Application to U.S. FDA Seeking Approval of Erdafitinib for the Treatment of Metastatic Urothelial Cancer
September 19, 2018 - Neuroplasticity is increased but dysregulated in the aging brain, study finds
September 19, 2018 - Suicide: A public health crisis
September 19, 2018 - Infants using popular anti-reflux medicines are not at increased risk of lung infections
September 19, 2018 - Stanford team will participate in NIH-funded study of tobacco policies | News Center
September 19, 2018 - Women with high levels of anti-Müllerian hormone more likely to develop breast cancer
September 19, 2018 - Researchers use larval zebrafish model to reveal role of locus coeruleus in anesthesia
September 19, 2018 - Effects of prematurity found to be more severe for the brains of males than females
September 19, 2018 - NIH funds CWRU to investigate new imaging approach for diagnosing peripheral arterial disease
September 19, 2018 - NUS researchers develop new device for quick and accurate screening of diseases
September 19, 2018 - Leading nutritionist explains about different types of iron in oral supplements
September 19, 2018 - New Crest Gum & Enamel Repair toothpaste may boost enamel repair and reverse gingivitis
September 19, 2018 - Analysis does not find any safety concerns of bivalent HPV vaccine
September 19, 2018 - Many Older Adults Transition to Long-Term Benzodiazepine Use
September 19, 2018 - Caregiving – resources – older adults: MedlinePlus Medical Encyclopedia
September 19, 2018 - Research shows that cystic fibrosis impacts growth in the womb
September 19, 2018 - Study shows how head, neck positioning affects concussion risk | News Center
September 19, 2018 - Antioxidant in green tea helps sneak therapeutic RNAs into cells
September 19, 2018 - Excess pregnancy weight gain affects cardiometabolic risk in offspring
September 19, 2018 - Penn researchers find common thread linking almost all TNR expansion diseases
September 19, 2018 - Ipsen receives approval from Health Canada for CABOMETYX tablets for treating renal cell carcinoma
September 19, 2018 - Researchers use CRISPR screen to reveal new targets in squamous cell carcinomas
September 19, 2018 - UGR to coordinate the European H2020 project focused on Smart Personalized Nutrition
September 19, 2018 - Mumps Spread Quickly at Texas Cheerleading Meets: Study
September 19, 2018 - Addressing child stunting in Pakistan is critical
September 19, 2018 - Innovative system makes hospitals, clinics accessible for people with visual impairments
September 19, 2018 - CXCL14 protein is secreted by brown adipose tissue and has beneficial effects in metabolic diseases
September 19, 2018 - Air pollution increases risk of dementia
September 19, 2018 - Inequality issues persist even under new U.S. kidney transplant allocation system
September 19, 2018 - New study reveals mechanisms that lead to cognitive decline in Type 2 diabetes
September 19, 2018 - FDA launches new comprehensive effort to educate kids about dangers of e-cigarettes
September 19, 2018 - Study reveals mechanism underlying plants’ ability to signal defense
September 19, 2018 - Researchers harness Zika virus vaccine under development to target glioblastoma
September 19, 2018 - Novel deep learning drug discovery platform gets £1 million innovation boost
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