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Studies assessing mechanisms of proximal tubular cell (PTC) physiology and pathophysiology increasingly utilize cell culture systems to avoid the complexity of whole organ/whole animal experiments. However, no well-differentiated PTC line derived from adult human kidney currently exists. Therefore, the goal of this research was to establish such a line by(More)
The mevalonate pathway produces many critical substances in cells, including sterols essential for membrane structure and isoprenoids vital to the function of many membrane proteins. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is a rate-limiting enzyme in the mevalonate pathway. Because cholesterol is a product of this pathway, HMG-CoA(More)
Cholesterol levels are abnormally increased in many acute myeloid leukemia (AML) samples exposed in vitro to chemotherapy. Blocking these acute cholesterol responses selectively sensitizes AML cells to therapeutics. Thus, defining the molecular mechanisms by which AML cells accomplish these protective cholesterol increments might elucidate novel therapeutic(More)
The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is a rate-limiting enzyme in the mevalonate biochemical pathway and HMG-CoA reductase inhibitors (statins) show toxicity for certain tumors, including acute myeloid leukemia (AML). This toxicity has been attributed to statin inhibition of Ras isoprenylation in tumors like AML where oncogenic ras(More)
BACKGROUND Experimental and clinical investigations suggest that oxidant stress is a critical determinant of radiocontrast nephropathy (RCN), and that N acetyl cysteine (NAC) can prevent this damage. This study addresses these issues directly at the tubular cell level. Potential alternative mechanisms for RCN have also been sought. METHODS Isolated mouse(More)
  • R A Zager
  • 1989
To explore why urine pH affects myoglobin (M)-induced renal injury, rats were infused with M under aciduric (NH4Cl) or alkalinuric (KHCO3) conditions with or without additional solute loading. Acute renal M retention (R) was highly pH dependent (pH 5.77, 68% R; pH 6.45, 49% R; pH 8.0, 28% R), the % R positively affecting the severity of renal injury(More)
This study assessed whether endothelin-1 (ET-1) helps mediate postischemic acute kidney injury (AKI) progression to chronic kidney disease (CKD). The impact(s) of potent ETA or ETB receptor-specific antagonists (Atrasentan and BQ-788, respectively) on disease progression were assessed 24 h or 2 weeks following 30 min of unilateral ischemia in CD-1 mice.(More)
Hemopexin (Hpx) is a liver-generated acute phase reactant that binds and neutralizes prooxidant free heme. This study tested whether acute kidney injury (AKI) triggers renal Hpx accumulation, potentially impacting heme Fe-mediated tubular injury. Mice were subjected to glycerol, cisplatin, ischemia-reperfusion (I/R), or endotoxemic [lipopolysaccharide(More)
BACKGROUND Carbon dioxide absorbents degrade sevoflurane, particularly at low gas flow rates, to fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A). Compound A causes renal proximal tubular injury in rats but has had no effect on blood urea nitrogen (BUN) or creatinine concentrations in patients. This investigation compared the effects of(More)