Differential expression of Na,K-ATPase ?-isoform mRNAs in aging rat cerebellum

Chauhan, Neelima B.; Siegel, George J.

doi:10.1002/(sici)1097-4547(19970201)47:3<287::aid-jnr7>3.0.co;2-e

Cited by 15 publications

(6 citation statements)

References 42 publications

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“…Thus, Atp1a1(−) Atp1a3(++) cells such as PV neurons would be more vulnerable to Amyloid β oligomers than Atp1a1 positive cells. The expression level of Atp1a3 and Atp1a1 in the aged rat brain is different from that in the young rat brain (N. Chauhan & Siegel, 1997a, 1997bN. B. Chauhan & Siegel, 1996).…”

Section: Discussionmentioning

confidence: 70%

Region‐ and neuronal‐subtype‐specific expression of Na,K‐ATPase alpha and beta subunit isoforms in the mouse brain

Murata

Kinoshita

Ishikawa

et al. 2020

J of Comparative Neurology

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Na,K‐ATPase is a ubiquitous molecule contributing to the asymmetrical distribution of Na+ and K+ ions across the plasma membrane and maintenance of the membrane potential, a prerequisite of neuronal activity. Na,K‐ATPase comprises three subunits (α, β, and FXYD). The α subunit has four isoforms in mice, with three of them (α1, α2, and α3) expressed in the brain. However, the functional and biological significances of the different brain isoforms remain to be fully elucidated. Recent studies have revealed the association of Atp1a3, a gene encoding α3 subunit, with neurological disorders. To map the cellular distributions of the α subunit isoforms and their coexpression patterns, we evaluated the mRNA expression of Atp1a1, Atp1a2, and Atp1a3 by in situ hybridization in the mouse brain. Atp1a1 and Atp1a3 were expressed in neurons, whereas Atp1a2 was almost exclusively expressed in glial cells. Most neurons coexpressed Atp1a1 and Atp1a3, with highly heterogeneous expression levels across the brain regions and neuronal subtypes. We identified parvalbumin (PV)‐expressing GABAergic neurons in the hippocampus, somatosensory cortex, and retrosplenial cortex as an example of a neuronal subtype expressing low Atp1a1 and high Atp1a3. The expression of Atp1b isoforms was also heterogeneous across brain regions and cellular subtypes. The PV‐expressing neurons expressed a high level of Atp1b1 and a low level of Atp1b2 and Atp1b3. These findings provide basic information on the region‐ and neuronal‐subtype‐dependent expression of Na,K‐ATPase α and β subunit isoforms, as well as a rationale for the selective involvement of neurons expressing high levels of Atp1a3 in neurological disorders.

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Section: Discussionmentioning

confidence: 70%

Region‐ and neuronal‐subtype‐specific expression of Na,K‐ATPase alpha and beta subunit isoforms in the mouse brain

Murata

Kinoshita

Ishikawa

et al. 2020

J of Comparative Neurology

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“…In a similar study (Hieber et al, 1991) which also investigated the cerebellum from rat, the antisense probe for α 3 NKA transcripts strongly labeled Purkinje cells as well, but it also labeled basket and stellate cells, and modest labeling was seen in the granule cell layer. Yet another in situ hybridization study mapping α 3 -NKA transcripts in the rat cerebellum (Chauhan and Siegel, 1997), showed large clusters of label on stellate, basket, Golgi, and Purkinje cells, with Purkinje cells being the most prominently labeled.…”

Section: Cerebellummentioning

confidence: 98%

A Transgenic Mouse Model to Selectively Identify α3 Na,K-ATPase Expressing Cells in the Nervous System

et al. 2019

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The α Na,K-ATPase (αNKA) is one of four known α isoforms of the mammalian transporter. A deficiency in αNKA is linked to severe movement control disorders. Understanding the pathogenesis of these disorders is limited by an incomplete knowledge of αNKA expression in the brain as well as the challenges associated with identifying living cells that express the isoform for subsequent electrophysiological studies. To address this problem, transgenic mice were generated on the C57BL/6 genetic background, which utilize the mouse α subunit gene (Atp1a3) promoter to drive the expression of ZsGreen1 fluorescent protein. Consistent with published results on αNKA distribution, a ZsGreen1 signal was detected in the brain, but not in the liver, with Atp1a3-ZsGreen1 transgenic mice. The intensity of ZsGreen1 fluorescence in neuronal cell bodies varied considerably in the brain, being highest in the brainstem, deep cerebellar and select thalamic nuclei, and relatively weak in cortical regions. Fluorescence was not detected in astrocytes or white matter areas. ZsGreen1-positive neurons were readily observed in fresh (unfixed) brain sections, which were amenable to patch-clamp recordings. Thus, the αNKA-ZsGreen1 mouse model provides a powerful tool for studying the distribution and functional properties of αNKA-expressing neurons in the brain.

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“…In fact, altered expression and activity of Na + , K + -ATPase have been observed in patients with Alzheimer's disease [47][48][49][50], diabetes [51], hypertension [52] and cancers [53][54][55][56][57]. Intracellular sodium and potassium become elevated and depressed, respectively, in many tumors, suggesting that mechanisms governing intracellular homeostasis for sodium and potassium are no longer tightly regulated in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Sodium/potasium ATPase (Na+, K+-ATPase) and ouabain/related cardiac glycosides: a new paradigm for development of anti- breast cancer drugs?

Chen

Contreras

Wang

et al. 2005

Breast Cancer Res Treat

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Prolonged exposure to 17beta-estradiol (E2) is a key etiological factor for human breast cancer. The biological effects and carcinogenic effects of E2 are mediated via estrogen receptors (ERs), ERalpha and ERbeta. Anti-estrogens, e.g. tamoxifen, and aromatase inhibitors have been used to treat ER-positive breast cancer. While anti-estrogen therapy is initially successful, a major problem is that most tumors develop resistance and the disease ultimately progresses, pointing to the need of developing alternative drugs targeting to other critical targets in breast cancer cells. We have identified that Na+, K+-ATPase, a plasma membrane ion pump, has unique/valuable properties that could be used as a potentially important target for breast cancer treatment: (a) it is a key player of cell adhesion and is involved in cancer progression; (b) it serves as a versatile signal transducer and is a target for a number of hormones including estrogens and (d) its aberrant expression and activity are implicated in the development and progression of breast cancer. There are several lines of evidence indicating that ouabain and related digitalis (the potent inhibitors of Na+, K+-ATPase) possess potent anti-breast cancer activity. While it is not clear how the suggested anti-cancer activity of these drugs work, several observations point to ouabain and digitalis as being potential ER antagonists. We critically reviewed many lines of evidence and postulated a novel concept that Na+, K+-ATPase in combination with ERs could be important targets of anti-breast cancer drugs. Modulators, e.g. ouabain and related digitalis could be useful to develop valuable anti-breast cancer drugs as both Na+, K+-ATPase inhibitors and ER antagonists.

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Differential expression of Na,K-ATPase ?-isoform mRNAs in aging rat cerebellum

Cited by 15 publications

References 42 publications

Region‐ and neuronal‐subtype‐specific expression of Na,K‐ATPase alpha and beta subunit isoforms in the mouse brain

Region‐ and neuronal‐subtype‐specific expression of Na,K‐ATPase alpha and beta subunit isoforms in the mouse brain

A Transgenic Mouse Model to Selectively Identify α3 Na,K-ATPase Expressing Cells in the Nervous System

Sodium/potasium ATPase (Na+, K+-ATPase) and ouabain/related cardiac glycosides: a new paradigm for development of anti- breast cancer drugs?

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