Journal News

MCP: Tracing damage pathways
in diabetic kidney disease

John Arnst
April 01, 2017

Diabetic kidney disease is the most common cause of kidney failure and can occur as a complication of both Type I and Type II diabetes. In a paper published in the journal of Molecular & Cellular Proteomics, researchers at the University of Toronto and the Institut Hospital del Mar d’Investigacions Mèdiques in Spain report a link between the proteomic changes caused by high levels of male sex hormones and impaired energy metabolism in diabetic kidney disease.

 


Patients with diabetic kidney disease can have kidneys with scarred glomeruli.
WIKIMEDIA COMMONS

“It’s been reported in previous clinical studies that male sex hormones predispose (patients) to many kidney diseases and lead to a more rapid progression and increased severity of kidney disease,” says Sergi Clotet, the first author on the paper and a postdoctoral researcher in the laboratory of Ana Konvalinka at the University of Toronto. “Our findings proposed this novel link between male sex (hormones), energy metabolism and oxidative stress in the kidneys of diabetic animals, which are indicators of mitochondrial damage.”

Diabetic kidney disease causes the clustered kidney capillaries, known as glomeruli, to leak high levels of proteins, such as albumin, into urine. The leakage eventually leads to anemia, chemical imbalance in the bloodstream and overall decline in kidney function. The disease can be stemmed if caught early on but may be exacerbated in men by elevated androgens.

Clotet and colleagues used a variation of the SILAC technique for their study. In traditional SILAC, which stands for stable-isotope labeling of amino acids in cell culture, the amino acids in cells are labeled with nonradioactive isotopes and quantified by mass spectrometry.

The SILAC variant, known as “spike-in,” enabled the investigators to bypass difficulties involved with labeling the primary proximal tubular cells, which don’t grow well in SILAC media, by labeling only transformed proximal tubular cells. The labeled transformed cell lysates then were combined with the unlabeled and stimulated primary cell lysates.

The investigators stimulated primary cells with 100 nanomolar doses of a sex hormone, either estradiol or dihydrotestosterone, and subjected them to mass spectrometry to identify the changes in metabolic regulation caused by each hormone.

After performing subsequent bioinformatics analyses, the researchers noticed that energy metabolism was impaired in the cells exposed to dihydrotestosterone. They validated their results by examining the expression of key enzymes involved in metabolism in kidneys of male and female normal and diabetic animals. The researchers then performed an enrichment analysis of their own data and a publicly available gene-expression data set generated from kidneys of patients with diabetes. With the analysis, the researchers were able to group and visualize significant functional categories. They found that oxidative stress was elevated significantly in the testosterone-treated samples from their dataset as well as in the kidneys of diabetic patients.

The researchers then decided to analyze oxidative stress levels and the sex differences in their animal groups, finding that the stress levels were increased in males of both normal and diabetic animals. “It’s a result that suggests that male sex is associated with more severe kidney disease,” says Clotet.

Clotet and colleagues intend to collect kidney biopsies from diabetic and nondiabetic male and female donors to validate their findings further as well as to look for biomarkers that could indicate early onset of diabetic kidney disease. “That could be a noninvasive way to predict sex-specific progression of diabetic and nondiabetic kidney diseases,” says Clotet. “At the end of the day, we want to explore more personalized treatments for kidney disease.”

John Arnst

John Arnst is a science writer for ASBMB Today.

Join the ASBMB Today mailing list

Sign up to get updates on articles, interviews and events.

Latest in Science

Science highlights or most popular articles

COVID-19 retractions show that the science is working as it should
Life in the Lab

COVID-19 retractions show that the science is working as it should

July 12, 2020

Severe scrutiny of two major papers, including one about the effectiveness of hydroxychloroquine, is part of science's normal process of self-correction, explains Mark R. O’Brian.

In the future, lab mice will live in computer chips, not cages
Life in the Lab

In the future, lab mice will live in computer chips, not cages

July 11, 2020

As COVID-19 shuttered laboratories across the U.S., many researchers were forced to euthanize the animals they study. Lindsay Gray, a rodent surgeon in an animal research lab that faced this dilemma, argues here there is a safer, more effective way.

Proteomics reveals hallmarks of aging in brain stem cells
Journal News

Proteomics reveals hallmarks of aging in brain stem cells

July 09, 2020

Early in adulthood, the brain regenerates lost myelin effectively, but remyelination falters with age. Researchers seek to understand why — and what the change may mean for people with multiple sclerosis.

Ocean virus hijacks carbon-storing bacteria
Journal News

Ocean virus hijacks carbon-storing bacteria

July 07, 2020

A Journal of Biological Chemistry paper reports that these minuscule interactions could have ripple effects on global carbon dioxide levels.

CRISPR nanoparticles are the next big hope in Alzheimer’s disease treatments
News

CRISPR nanoparticles are the next big hope in Alzheimer’s disease treatments

July 04, 2020

Nearly 6 million Americans live with Alzheimer’s disease without solid treatment options.

Summer food science
Stroopwafels

Summer food science

July 02, 2020

For those of you bound for a summertime holiday weekend, we dug into recent research on the yummy foods you might serve at a socially distant picnic.