Abstract: FR-PO216
Inhibiting Na/K-ATPase Oxidant Amplification Loop Regulates Aging in C57B16 Old Mice
Session Information
- Apoptosis, Proliferation, Autophagy, Cell Senescence, Cell Transformation
November 03, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Cell Biology
- 202 Apoptosis, Proliferation, Autophagy, Cell Senescence, Cell Transformation
Authors
- Klug, Rebecca Lynn, Marshall University, Joan C. Edwards School of Medicine , Huntington, West Virginia, United States
- Nichols, Alexandra, MUSOM , Huntington, West Virginia, United States
- Snoad, Brian J, Marshall University, Huntington, West Virginia, United States
- Lakhani, Hari Vishal, Marshall University, Huntington, West Virginia, United States
- Shapiro, Joseph I., Marshall University School of Medicine, Huntington, West Virginia, United States
- Sodhi, Komal, Marshall University, Joan C. Edwards School of Medicine , Huntington, West Virginia, United States
Background
Aging, the inevitable and progressive decline of physiological integrity, manifests as: loss of cell division, oxidative stress, DNA damage, and senescence gene overexpression. Oxidant stress plays a role in the aging process, presumably in cellular and DNA damage. This contributes to impaired physiological function, disease development, and life span reduction. As we identified, the Na/K-ATPase amplifies oxidant signaling; we speculate a peptide inhibiting this pathway, pNaKtide, may be effective to regulate cellular senescence, thus delaying and/or reversing aging by attenuating oxidative stress.
Methods
C57Bl6 mice, young (6-8 weeks old, male) and old (17 weeks old, male) were fed normal chow diet or Western Diet (WD). They were randomly divided into 6 groups: (1) Young Control, (2) Young+pNaKtide (3) Old+Control, (4) Old+pNaKtide (5) Old+WD, (6) Old+WD+pNaKtide. After 8 weeks of control or WD diet respectively, groups 2, 4 and 6 were injected with pNaKtide for 8 weeks, (intraperitoneal dose of 25-mg/kg-body weight every 7 days).
Results
Histological analysis of liver shows increased steatosis and fibrosis with age and more so with WD, this decreased with pNaKtide treatment. Histological analysis of kidney shows increased fat infiltration and sclerosis with age and WD, which decreased with pNaKtide treatment. TUNEL assay of liver and kidney indicated more DNA damage with age and WD, this significantly decreased with pNaKtide treatment (p≤0.05). Indicative of oxidative stress, carbonylation of the Na/K-ATPase α1-subunit, activation of p-Src and TBARS were significantly elevated in old and WD liver and kidney compared to those given pNaKtide treatment (p≤0.05). RT-PCR of senescence genes: p21, Apo lipoprotein J, Collagenase 1, fibronectin, and MMP-9 were significantly increased in hepatic and renal tissue with age and WD compared to those given pNaKtide treatment (p≤0.05).
Conclusion
Our study demonstrates that Na/K-ATPase regulates aging and pNaKtide significantly alleviates genetic and phenotypic attributes of aging. pNaKtide holds potential as a novel drug for treating cellular damage that contributes to manifestations of aging and WD.
Funding
- Other NIH Support –