Chronic kidney disease (CKD), an affliction characterized by progressive loss of kidney function, affects millions of people worldwide and is associated with multi-organ damage, cardiovascular disease, and muscle wasting. Just like engines, living cells require energy to run, thus the combined millions of cells forming an organ have huge energy requirements. Although the heart has the highest energy needs of all human organs, the kidneys come a close second. Energy depletion can result in kidney damage and the build-up of toxic compounds in the body, contributing to the progression of CKD. Currently, there is no effective treatment to halt this progression.
Adenosine triphosphate (ATP) is the major "fuel" in most living cells and is converted to adenosine monophosphate (AMP) during energy transfer. A specialized energy sensor called 5?-AMP-activated protein kinase (AMPK) detects even the slightest changes in cellular energy by sensing AMP levels, triggering the production of ATP in response to energy depletion. However, AMPK activity is decreased in CKD and the mechanism controlling this dysregulation is unclear.
Now, a research team has shown that failure to sense AMP is the key mechanism underlying the inactivity of AMPK in CKD. In a recent study published in Kidney International, they outline how they came to this conclusion and what it may mean for CKD patients.
"Metabolites can tell us a lot about what's going on in a cell," explains lead author. "In CKD mice, metabolite profiling showed that despite high levels of AMP, there was a substantial decrease in AMPK activation, leading us to conclude that the AMP-sensing function of AMPK was defective."
Armed with this new information, the researchers tried bypassing the AMP-sensing mechanism to determine whether AMPK could still be activated in CKD mice. By treating the mice with A-769662, an AMPK activator that binds at a different site to AMP, they could significantly attenuate CKD progression and correct associated tissue damage.
Critically, the build-up of waste products in the blood as a result of reduced kidney function was shown to be responsible for the decreased AMP-sensing activity of AMPK. "Our findings suggest that energy depletion, CKD progression, and the accumulation of toxic metabolites form a vicious cycle in CKD patients," says co-corresponding author. "However, AMPK activation via AMP-independent mechanisms can break this cycle and represents a novel therapeutic approach for the treatment of CKD."
http://www.tmd.ac.jp/english/press-release/20181207_1/index.html
https://www.kidney-international.org/article/S0085-2538(18)30635-5/fulltext
Cellular energy sensor linked to the progression of chronic kidney disease
- 1,236 views
- Added
Edited
Latest News
Complete vascularization of…
By newseditor
Posted 28 Mar
Immune cells identified as…
By newseditor
Posted 28 Mar
TB blood test which could d…
By newseditor
Posted 27 Mar
Propionate supplementation…
By newseditor
Posted 27 Mar
Role of human Kallistatin i…
By newseditor
Posted 26 Mar
Other Top Stories
Kinase acts like a transcription factor in breast cancer
Read more
Identification of Distinct Breast Cancer Stem Cell Populations Base…
Read more
Anti-apoptotic protein promotes metastasis
Read more
Metabolic Reprogramming of Pancreatic Cancer by Certain Drugs
Read more
Promoting Sensitivity to Anti-folate Therapy in Breast Cancer
Read more
Protocols
Spatial proteomics in neuro…
By newseditor
Posted 28 Mar
All-optical presynaptic pla…
By newseditor
Posted 23 Mar
Epigenomic tomography for p…
By newseditor
Posted 20 Mar
A mouse DRG genetic toolkit…
By newseditor
Posted 17 Mar
An optogenetic method for t…
By newseditor
Posted 13 Mar
Publications
A microfluidic platform int…
By newseditor
Posted 28 Mar
Salmonella manipulates macr…
By newseditor
Posted 28 Mar
BHLHE40/41 regulate microgl…
By newseditor
Posted 28 Mar
Balancing neuronal activity…
By newseditor
Posted 28 Mar
OSBP-mediated PI(4)P-choles…
By newseditor
Posted 28 Mar
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar