Transport by the (Na<sup>+</sup>, K<sup>+</sup>) ATPase: Modulation by differentiation inducers and inhibition of protein synthesis in the MDCK kidney epithelial cell line

Kennedy, Brian G.; Lever, Julia E.

doi:10.1002/jcp.1041230317

Cited by 18 publications

(8 citation statements)

References 33 publications

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“…Some authors reported ouabain binding site in MDCK similar to ours (27). A rather low turnover rate in MDCK cells has been also previously reported (21). It may be speculated that ATP concentration in MDCK cells, but not in HEK, is limiting for Na-K-ATPase activity, in keeping with the previously demonstrated effect of adducin that increases Na-K-ATPase activity by enhancing the affinity for ATP (11).…”

Section: Discussionsupporting

confidence: 56%

α-Adducin mutations increase Na/K pump activity in renal cells by affecting constitutive endocytosis: implications for tubular Na reabsorption

Torielli¹,

Tivodar²,

Montella³

et al. 2008

American Journal of Physiology-Renal Physiology

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Genetic variation in α-adducin cytoskeletal protein is implicated in the polymerization and bundling of actin and alteration of the Na/K pump, resulting in abnormal renal sodium transport and hypertension in Milan hypertensive rats and humans. To investigate the molecular involvement of α-adducin in controlling Na/K pump activity, wild-type or mutated rat and human α-adducin forms were, respectively, transfected into several renal cell lines. Through multiple experimental approaches (microscopy, enzymatic assays, coimmunoprecipitation), we showed that rat and human mutated forms increased Na/K pump activity and the number of pump units; moreover, both variants coimmunoprecipitate with Na/K pump. The increased Na/K pump activity was not due to changes in its basolateral localization, but to an alteration of Na/K pump residential time on the plasma membrane. Indeed, both rat and human mutated variants reduced constitutive Na/K pump endocytosis and similarly affected transferrin receptor trafficking and fluid-phase endocytosis. In fact, α-adducin was detected in clathrin-coated vesicles and coimmunoprecipitated with clathrin. These results indicate that adducin, besides its modulatory effects on actin cytoskeleton dynamics, might play a direct role in clathrin-dependent endocytosis. The constitutive reduction of the Na/K pump endocytic rate induced by mutated adducin variants may be relevant in Na-dependent hypertension.

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Section: Discussionsupporting

confidence: 56%

α-Adducin mutations increase Na/K pump activity in renal cells by affecting constitutive endocytosis: implications for tubular Na reabsorption

Torielli¹,

Tivodar²,

Montella³

et al. 2008

American Journal of Physiology-Renal Physiology

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“…Several studies in animals demonstrate a reduction in Na + - K + - ATPase activity in heart (Poole et al, 1984) and brain (Poole et al, 1984; Tanaka and Ando, 1990) tissue with added support in human erythrocytes (Poehlman et al, 1993) and lymphocytes (Witkowski et al, 1985). Although there is some conflicting evidence (Kennedy and Lever, 1985), the predominance of evidence suggests a reduction Na + - K + - ATPase that may contribute to the reduction in RMR seen with aging.…”

Section: Total Energy Expenditure and Agingmentioning

confidence: 99%

Energy expenditure and aging

Manini

2010

Ageing Research Reviews

222

143

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The study of energy expenditure (EE) has deep roots in understanding aging and lifespan in all species. In humans, total EE decreases substantially in advanced age resulting from parallel changes in resting metabolic rate (RMR) and activity EE. For RMR, this reduction appears to be due to a reduction in organ mass and specific metabolic rates of individual tissues. However, these anatomical changes explain very little regarding the decline in activity EE, which is governed by both genetic and environmental sources. The biological control centers for activity EE are closely coupled with body mass fluctuations and seem to originate in the brain. Several candidate neuromodulators may be involved in the age-related reduction of activity EE that include: orexin, agouti-related proteins and dopaminergic pathways. Unfortunately, the existing body of research has primarily focused on how neuromodulators influence weight gain and only a few studies have been performed in aging models. Recent evidence suggests that activity EE has an important role in dictating lifespan and thus places emphasis on future research to uncover the underlying biological mechanisms. The study of EE continues to unlock clues to aging. IntroductionAmong the enormous literature on theoretical explanations of aging the role of energy expenditure (EE) has received the most attention. For thousands of years, energy expenditure and metabolism have provided an understanding of how we function today, tomorrow, and eventually when we cease to function altogether. The study of EE and aging has been spurred along by the intriguing association between high rates of EE in short-lived mammals and low rates of EE in long-lived mammals. Some propose that EE per lifespan is fixed and abundant usage will accelerate aging (Rubner, 1908). While many works have challenged and severely criticized the rate of living theory (Holloszy and Smith, 1986;Austad and Fischer, 1991), EE and the biological processes that control the machinery are very much under intense study (Speakman, 2005).Energy expenditure has often been purported as a cause of aging without a complete understanding of changes in each of EE components with age. A thorough understanding of the age-related changes in EE components will help reveal the potential compensatory strategies that preserve lifespan. For example, it remains unclear why EE due to physical activity declines across all mammalian phylogenetic lines. Although many hypotheses on aging have involved in some manner the rates of metabolism, the debate on the role of altering EE for enhancing lifespan continues with new data in humans (Manini et al., 2006). The results add new light to the role of EE in preserving average lifespan among older adults.Correspondence: Todd Manini, University of Florida, Institute on Aging, Department of Aging and Geriatric Research, 210 E Mowry Rd, PO Box 112610, Gainesville, FL 32611-2610, tmanini@aging.ufl.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted ...

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“…This is achieved after a 24-hr incubation with inducers, requires de novo protein synthesis, and involves a 30 to 40% reduction in the transport efficiency of the Na,K-ATPase (6,19). The significance of this finding is underscored by the observation that inducerresistant variants were refractory to pump inhibition by HMBA (18 differentiation therapy (23).…”

Section: Mechanism Of Action Of Inducersmentioning

confidence: 99%

Chemical Inducers of Differentiation in a Long-Term Renal Cell Line

Lever¹

1989

Environmental Health Perspectives

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The long-term renal epithelial cell line LLC-PK1 expresses at confluence several differentiated characteristics of renal proximal tubule including Na/glucose cotransport and several brush border membrane hydrolases. The differentiation-inducing chemical hexamethylene bisacetamide (HMBA) triggers a dramatic induction of Na /glucose symport, trehalase and maltase, expressed as an increase in the number of cells in the culture that express the differentiated phenotype. Characteristics of the induction response are reviewed in terms of proposed mechanisms of inducer action. New evidence suggests that in addition to elevation of intracellular Na levels mediated by partial inhibition of the sodium pump, HMBA treatment also alters polyamine levels via effects on ornithine decarboxylase. These responses may be mediated by HMBA effects on protein kinase C activity. The possible role of polyamine fluctuations and DNA demethylation in mediating HMBA effects on differentiated gene expression is currently being investigated.

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Transport by the (Na⁺, K⁺) ATPase: Modulation by differentiation inducers and inhibition of protein synthesis in the MDCK kidney epithelial cell line

Cited by 18 publications

References 33 publications

α-Adducin mutations increase Na/K pump activity in renal cells by affecting constitutive endocytosis: implications for tubular Na reabsorption

α-Adducin mutations increase Na/K pump activity in renal cells by affecting constitutive endocytosis: implications for tubular Na reabsorption

Energy expenditure and aging

Chemical Inducers of Differentiation in a Long-Term Renal Cell Line

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Transport by the (Na+, K+) ATPase: Modulation by differentiation inducers and inhibition of protein synthesis in the MDCK kidney epithelial cell line

Cited by 18 publications

References 33 publications

α-Adducin mutations increase Na/K pump activity in renal cells by affecting constitutive endocytosis: implications for tubular Na reabsorption

α-Adducin mutations increase Na/K pump activity in renal cells by affecting constitutive endocytosis: implications for tubular Na reabsorption

Energy expenditure and aging

Chemical Inducers of Differentiation in a Long-Term Renal Cell Line

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Transport by the (Na⁺, K⁺) ATPase: Modulation by differentiation inducers and inhibition of protein synthesis in the MDCK kidney epithelial cell line