RETRACTED: Uremic Toxins Activates Na/K-ATPase Oxidant Amplification Loop Causing Phenotypic Changes in Adipocytes in...

Area of Science:

• Biochemistry
• Cell Biology
• Physiology

Background:

• Oxidative stress is a key factor in chronic kidney disease (CKD) development.
• Uremic toxins (UTs) accumulate in CKD, increasing reactive oxygen species (ROS) and activating the Na/K-ATPase/ROS amplification loop.
• Dysfunctional adipocytes contribute to oxidative stress in obesity and potentially in CKD.

Purpose of the Study:

• To investigate if UTs activate the Na/K-ATPase oxidant amplification loop in adipocytes.
• To determine if this activation causes redox imbalance and phenotypic alterations in adipocytes.
• To evaluate the efficacy of the Na/K-ATPase signaling antagonist, pNaKtide, in mitigating these effects.

Main Methods:

• 3T3-L1 murine pre-adipocytes and human mesenchymal stem cell (MSC)-derived adipocytes were treated with varying concentrations of UTs (indoxyl sulfate and p-cresol).
• Cells were co-treated with or without pNaKtide, a Na/K-ATPase signaling antagonist.
• Assays included Oil Red O staining for adipogenesis, RT-PCR for gene expression (adipogenic, apoptotic, inflammatory markers), and DHE staining for superoxide levels.

Main Results:

• UT exposure significantly decreased adipogenesis and induced apoptosis in both 3T3-L1 and MSC-derived adipocytes via the Na/K-ATPase/ROS loop.
• pNaKtide treatment counteracted UT effects, restoring cellular redox balance in adipocytes.
• The impact of pNaKtide varied across inflammatory and adipogenic markers and superoxide levels depending on the cell model.

Conclusions:

• UTs activate the Na/K-ATPase/ROS amplification loop, leading to varied phenotypic alterations in adipocytes.
• Inhibition of this amplification loop by pNaKtide shows promise in restoring adipocyte function.
• Targeting Na/K-ATPase-mediated oxidant stress may offer a novel therapeutic strategy for adipocyte dysfunction and metabolic imbalance in CKD patients.