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Publications (14)
The seven mammalian FXYD proteins associate closely with α/β heterodimers of Na+/K+-ATPase. Most of them protect the β1 subunit against glutathionylation, an oxidative modification that destabilizes the heterodimer and inhibits Na+/K+-ATPase activity. A specific cysteine (Cys) residue of FXYD proteins is critical for such protection. One of the FXY...
Background
FXYD proteins associate closely with- and protect plasmalemmal Na⁺/K⁺-ATPase against oxidative inhibition. One of them, FXYD3, is often overexpressed in cancers, including those of breast and pancreas. Down-regulation of overexpression in MCF-7 breast cancer cells with siRNA augments doxorubicin-induced cytotoxicity. Because down-regulat...
Rationale: Cardiotonic steroids (CTS), such as digoxin, have been used to treat heart failure (HF) for over 200 years. They inhibit the sodium-potassium pump (NKP), and increase cardiac contractility by inhibiting efflux of sodium through the pump (“digitalis hypothesis”). CTS possess three structural components: a saturated/unsaturated lactone rin...
Aims/Hypothesis
Developmental programming induced by maternal obesity influences the development of chronic disease in offspring. In the present study, we aimed to determine whether maternal obesity exaggerates obesity-related kidney disease.
Methods
Female C57BL/6 mice were fed high-fat diet (HFD) for six weeks prior to mating, during gestation a...
Tubular interstitial fibrosis.
Representative images of tubular interstitial fibrosis: A) tubular atrophy, B) tubular dilatation, C) inflammatory infiltrate, D) thickened basement membrane, E) widened interstitial space. Tubular interstitial fibrosis was scored using a scale of 0 to 4: 0 –normal; 1 –involvement of < 10% of the cortex; 2 –involvemen...
Tubular interstitial injury.
Representative images of tubular injury: A) tubular dilatation, B) tubular vacuolation, C) glycogenated nuclei, D) tubular casts). Tubular dilation was scored using a scale of 0 to 4. Tubular vacuolation was scored using a scale of 0 to 3. Glycogenated nuclei were scored using a scale of 0 to 3. Cast appearance was scor...
Glomerulosclerosis injury.
Representative images of glomerulosclerosis scored as A) 0 –no sclerosis, B) 1–25% sclerosis, c) 26–50% sclerosis, D) 51–75% sclerosis, E) > 75% sclerosis.
(TIFF)
Multiple rodent models have been used to study diabetic kidney disease (DKD). The purpose of the present study was to compare models of diabetes and obesity-induced metabolic syndrome and determine differences in renal outcomes. C57BL/6 male mice were fed either normal chow or high fat diet (HFD). At postnatal week 8, chow-fed mice were randomly as...
Maternal obesity is known to increase the risk of obesity and diabetes in offspring. Though diabetes is a key risk factor for the development of chronic kidney disease (CKD), the relationship between maternal obesity and CKD has not been clearly defined. In this study, a mouse model of maternal obesity was employed to determine the impact of matern...
FXYD3, also known as mammary tumor protein 8, is overexpressed in several common cancers, including in many breast cancers. We examined if such overexpression might protect Na(+)/K(+)-ATPase and cancer cells against the high levels of oxidative stress characteristic of many tumors and often induced by cancer treatments. We measured FXYD3 expression...
Aim: To determine whether maternal obesity accelerates the development of chronic kidney disease (CKD) in offspring with diabetes. Background: We have previously shown that maternal obesity is associated with adverse renal outcomes in offspring at an early time point. We hypothesised that a secondhit such as diabetes may further exacerbate renal d...