Breaking News
February 16, 2019 - Millions of British people breathe toxic air travelling to GPs
February 16, 2019 - Conformance of genetic characteristics found to be crucial for longer preservation of kidney graft
February 16, 2019 - Researchers use optogenetic tool to control, visualize receptor signals in neural cells
February 16, 2019 - New reversible antiplatelet therapy could reduce risk of blood clots, prevent cancer metastasis
February 16, 2019 - Testosterone is not the only hormone needed for penis development
February 16, 2019 - FDA Advisory Committee Recommends Approval of Spravato (esketamine) Nasal Spray for Adults with Treatment-Resistant Depression
February 15, 2019 - Heart surgery technology developed at Baptist Health debuts after years of secrecy
February 15, 2019 - Prescription Opioids Double Risk of Triggering Fatal Car Crash
February 15, 2019 - New study helps doctors better understand high blood pressure in pregnant women
February 15, 2019 - Beta wave control in Parkinson’s diseased brain could be a potential therapy
February 15, 2019 - Media representations of love may justify gender-based violence in young people
February 15, 2019 - Yoga May Help With Rheumatoid Arthritis Symptoms, Severity
February 15, 2019 - Obstructive sleep apnea linked to inflammation, organ dysfunction
February 15, 2019 - Master your mind: A challenge from WELL for Life
February 15, 2019 - Why Some Brain Tumors Respond to Immunotherapy
February 15, 2019 - Must-Reads Of The Week From Brianna Labuskes
February 15, 2019 - Researchers uncover novel mechanism and potential new therapeutic target for Alzheimer’s
February 15, 2019 - Genetic variations in a fourth gene associated with higher ALL risk in Hispanic children
February 15, 2019 - Disruptive behavioral problems in kindergarten linked with lower employment earnings in adulthood
February 15, 2019 - New bioengineered device enhances the production of T-cells
February 15, 2019 - HDL proteome behaves like a tiny Velcro ball that is rolling on surfaces
February 15, 2019 - Puerto Rican children more likely to have poor or decreasing use of asthma inhalers
February 15, 2019 - Quality of patient care does not improve after physician-hospital integration
February 15, 2019 - Synopsys release new software for implant design and patient-specific planning
February 15, 2019 - 6 out of 10 hip replacements last 25 years or longer
February 15, 2019 - Health Tip: What You Should Know About Antibiotics
February 15, 2019 - New research challenges medical consensus that adenoids and tonsils significantly shrink during teenage years
February 15, 2019 - Discovery of weakness in a rare cancer could be exploited with drugs
February 15, 2019 - UVA scientists find potential explanation for mysterious cell death in Alzheimer’s, Parkinson’s
February 15, 2019 - New rules requiring female athletes to lower testosterone levels are based on flawed data
February 15, 2019 - Researchers comprehensively sequence the human immune system
February 15, 2019 - Researchers study animal venoms to identify new medicines for treating diseases
February 15, 2019 - Movement of wrist bones revealed by MRI and computer modeling
February 15, 2019 - Philips introduces new premium digital X-ray room to help shorten patient wait times
February 15, 2019 - Women fare worse than men following aortic heart surgery, study finds
February 15, 2019 - High-protein and low-calorie diet helps older adults lose weight safely, shows study
February 15, 2019 - Drug microdosing effects may not measure up to big expectations
February 15, 2019 - Discharged, Dismissed: ERs Often Miss Chance To Set Overdose Survivors On ‘Better Path’
February 15, 2019 - A digitized lab environment to be showcased at smartLAB 2019
February 15, 2019 - Scientists uncover main mechanisms of fluconazole drug resistance
February 15, 2019 - New study seeks to understand how colibactin causes cancer
February 15, 2019 - Photoacoustic imaging accurately measures the temperature of deep tissues
February 15, 2019 - Large study finds no association between phthalate exposure and breast cancer risk
February 15, 2019 - New research explains presence of ‘natural’ magnetism in human cells
February 15, 2019 - Bio-Rad launches new digital PCR system and kit for monitoring treatment response in CML patients
February 15, 2019 - Excessive daytime sleepiness in OSA patients linked to greater risk for cardiovascular diseases
February 15, 2019 - Scientists shed light on damaging cell effects linked to aging
February 15, 2019 - Celiac disease may be caused by stomach bug in childhood
February 15, 2019 - NHS performance figures highlight the true scale of Emergency Department crisis
February 15, 2019 - High intensity exercise may improve health by increasing gut microbiota diversity
February 15, 2019 - Apellis’ APL-2 Receives Orphan Drug Designation from the FDA for the Treatment of Autoimmune Hemolytic Anemia
February 15, 2019 - Couples creating art or playing board games release ‘love hormone’
February 15, 2019 - Glimpsing The Future At Gargantuan Health Tech Showcase
February 15, 2019 - Common herbicide found to increase the risk of lymphoma
February 15, 2019 - Over-abundance of energy to cells could increase cancer risk
February 15, 2019 - Oxford Genetics appoints Jocelyne Bath as new Chief Operating Officer
February 15, 2019 - Castration-resistant metastatic prostate cancer responds to combination of immune checkpoint inhibitors
February 15, 2019 - Large-scale clinical trial begins to study liver transplantation between people with HIV
February 15, 2019 - Cannabis use among adolescents linked with increased risk of depression in adulthood
February 15, 2019 - Fractures, head injuries common in electric scooter accidents, UCLA study finds
February 15, 2019 - Prenatal maternal depression has important consequences for infant temperament, study shows
February 15, 2019 - Stereotactic body radiotherapy effective in treating men with low- or intermediate-risk prostate cancer
February 15, 2019 - Zogenix Submits New Drug Application to U.S. Food & Drug Administration for Fintepla for the Treatment of Dravet Syndrome
February 15, 2019 - Certain birthmarks warrant quick treatment, pediatricians say
February 15, 2019 - New machine learning method predicts if atypical ductal hyperplasia will turn cancerous
February 15, 2019 - Whole-genome sequencing and sharing real-time data could limit spread of foodborne bacteria
February 15, 2019 - FDA warns doctor for illegally marketing unapproved implantable device
February 15, 2019 - New injury documentation tool may provide better evidence for elder abuse cases
February 15, 2019 - Physiological age is a better predictor of survival than chronological age, shows study
February 15, 2019 - New study reveals high success rate for hip and knee replacements
February 15, 2019 - Prenatal exposures to BPA may pose threat to human ovarian function
February 15, 2019 - Suspicious spots on the lungs of children with rhabdomyosarcoma do not behave like metastases
February 15, 2019 - Diet drinks daily could raise stroke risk says study
February 15, 2019 - Many Systematic Reviews Do Not Fully Report Adverse Events
February 15, 2019 - Seven tips to protect your child from burns
February 15, 2019 - Keynote speakers announced for CBD Expo MIDWEST
February 15, 2019 - New DNA methylation GrimAge tool allows you to predict lifespan and healthspan
February 15, 2019 - New AI-driven platform analyze how pathogens infect human cells
February 15, 2019 - Increased activity of EHMT2 gene deficient neurons could cause autism in humans
February 15, 2019 - Recurring UTIs may mask symptoms of bladder or kidney cancer
Enzyme discovery provides new horizon of therapeutic opportunities across disease spectrum

Enzyme discovery provides new horizon of therapeutic opportunities across disease spectrum

image_pdfDownload PDFimage_print

Doctors have long treated heart attacks, improved asthma symptoms, and cured impotence by increasing levels of a single molecule in the body: nitric oxide.

The tiny molecule can change how proteins function. But new research featured in Molecular Cell suggests supplementing nitric oxide- NO- is only the first step. Researchers have discovered previously unknown enzymes in the body that convert NO into “stopgap” molecules- SNOs- that then modulate proteins. The newly discovered enzymes help NO have diverse roles in cells. They may also be prime therapeutic targets to treat a range of diseases.

The discovery represents a paradigm shift for biologists in the field, says study lead Jonathan Stamler, MD, professor of medicine at Case Western Reserve University School of Medicine and President, University Hospitals Harrington Discovery Institute.

“Nitric oxide has been implicated in virtually all cellular functions, and too much or too little is widely implicated in disease, including Alzheimer’s, heart failure, cancer, asthma and infection,” he explained. “The prevailing view in the field is that too much or too little NO is due to activity of enzymes that make NO, called NO synthases. However, the new findings suggest that NO synthases operate in concert with two new classes of enzymes that attach NO to target proteins, and raise the possibility of literally hundreds of enzymes mediating NO-based signaling.”

The enzymes work together to control proteins through a process called S-nitrosylation. Stamler and colleagues describe a chain reaction. First, NO synthases make NO. Then, a new class of enzymes-;SNO synthases-;convert NO into SNOs, that attach to proteins and modulate their function. A third class transfers the SNOs to additional proteins that control numerous additional cellular functions, including growth, movement and metabolism, and also protect cells from injury. Without SNO synthases, cells can’t use NO. And there are potentially hundreds of different SNO–generating enzymes that make thousands of different SNOs.

NO signaling in cells is essentially designed to make SNOs-;lots of them.

“This opens the field to new understanding and opportunity, as hundreds of enzymes likely carry out signaling inside cells through this process. Each of these enzymes could potentially be targeted specifically in disease,” Stamler said.

With so many enzymes in the new model, it now makes sense why drugs that increase NO levels are not interchangeable. “The assumption is that they all work the same way to increase NO. But our findings suggest that NO itself is just the first step. It’s all in what the cell does with NO and which SNO it’s converted into,” Stamler said. “Administration of NO cannot replicate the function of SNOs carried out by these new enzymes.”

The groundbreaking study finally explains how NO can have so many different functions in cells. By converting NO into different SNOs, cells can achieve different results.

The next step for researchers will be to identify individual SNO synthases in different tissues and their specific roles in disease, says Stamler. The new enzymes could serve as therapeutic targets for drug developers. For example, excessive S-nitrosylation is strongly associated with Alzheimer’s and Parkinson’s diseases, but NO is also needed for normal brain function, including memory.

“The assumption has been that one has to block NO production to stop this from happening. But the treatments don’t work,” he said. Since NO has such sweeping effects inside cells, blocking it has major side effects. Under the new model, researchers could target disease-specific SNO synthases working downstream of NO.

“Now we know that we can block S-nitrosylation without altering NO production,” Stamler said. “This provides a new horizon of therapeutic opportunities, and changes perspective in the field.”

Source:

http://casemed.case.edu/cwrumed360/news-releases/release.cfm?news_id=910

Tagged with:

About author

Related Articles