Targeting of renal proximal tubule Na,K-ATPase by salt-inducible kinase

Taub, Mary; Springate, James E.; Cutuli, Facundo

doi:10.1016/j.bbrc.2010.02.037

Cited by 35 publications

(25 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 Although the p.(Pro287Thr)-expressing neurons did not demonstrate the same degree of abnormality in MEF2C and ARC expression, it is possible that the severe phenotype associated with this sequence variation is conferred through another mechanism. For example, it is known that SIK1 directly regulates Na-K ATPases in the renal proximal tubule and vascular smooth muscle, 40,41 and dysfunction of that pathway in neurons may be another mechanism where seizures might be generated.…”

Section: Discussionmentioning

confidence: 99%

Epilepsy-causing sequence variations in SIK1 disrupt synaptic activity response gene expression and affect neuronal morphology

et al. 2016

View full text Add to dashboard Cite

SIK1 syndrome is a newly described developmental epilepsy disorder caused by heterozygous mutations in the salt-inducible kinase SIK1. To better understand the pathophysiology of SIK1 syndrome, we studied the effects of SIK1 pathogenic sequence variations in human neurons. Primary human fetal cortical neurons were transfected with a lentiviral vector to overexpress wild-type and mutant SIK1 protein. We evaluated the transcriptional activity of known downstream gene targets in neurons expressing mutant SIK1 compared with wild type. We then assayed neuronal morphology by measuring neurite length, number and branching. Truncating SIK1 sequence variations were associated with abnormal MEF2C transcriptional activity and decreased MEF2C protein levels. Epilepsy-causing SIK1 sequence variations were associated with significantly decreased expression of ARC (activity-regulated cytoskeletal-associated) and other synaptic activity response element genes. Assay of mRNA levels for other MEF2C target genes NR4A1 (Nur77) and NRG1, found significantly, decreased the expression of these genes as well. The missense p.(Pro287Thr) SIK1 sequence variation was associated with abnormal neuronal morphology, with significant decreases in mean neurite length, mean number of neurites and a significant increase in proximal branches compared with wild type. Epilepsy-causing SIK1 sequence variations resulted in abnormalities in the MEF2C-ARC pathway of neuronal development and synapse activity response. This work provides the first insights into the mechanisms of pathogenesis in SIK1 syndrome, and extends the ARX-MEF2C pathway in the pathogenesis of developmental epilepsy.

show abstract

Section: Discussionmentioning

confidence: 99%

Epilepsy-causing sequence variations in SIK1 disrupt synaptic activity response gene expression and affect neuronal morphology

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The authors suggested that, in the face of energy-deprivation, stimulation of AMPK may alleviate some of the epithelial cell damage by activating energy-conserving pathways. Indeed, Na + ,K + -ATPase expression and function may be regulated by AMPK and AMPK family members, such as the salt-inducible kinases (Taub et al , 2010). It is possible that similar energy-salvaging mechanisms are activated upon SIRT1 activation which restore Na + ,K + -ATPase expression and localization after I/R, although this has yet to be shown.…”

Section: Discussionmentioning

confidence: 99%

Accelerated recovery of renal mitochondrial and tubule homeostasis with SIRT1/PGC-1α activation following ischemia–reperfusion injury

Funk

Schnellmann

2013

Toxicology and Applied Pharmacology

146

View full text Add to dashboard Cite

Kidney ischemia-reperfusion (I/R) injury elicits cellular injury in the proximal tubule, and mitochondrial dysfunction is a pathological consequence of I/R. Promoting mitochondrial biogenesis (MB) as a repair mechanism after injury may offer a unique strategy to restore both mitochondrial and organ function. Rats subjected to bilateral renal pedicle ligation for 22 min were treated once daily with the SIRT1 activator SRT1720 (5 mg/kg) starting 24h after reperfusion until 72h–144h. SIRT1 expression was elevated in the renal cortex of rats after I/R + vehicle treatment (IRV), but was associated with less nuclear localization. SIRT1 expression was even further augmented and nuclear localization was restored in the kidneys of rats after I/R + SRT1720 treatment (IRS). PGC-1α was elevated at 72h–144h in IRV and IRS kidneys; however, SRT1720 treatment induced deacetylation of PGC-1α, a marker of activation. Mitochondrial proteins ATP synthase β, COX I, and NDUFB8, as well as mitochondrial respiration, were diminished 24h–144h in IRV rats, but were partially or fully restored in IRS rats. Urinary kidney injury molecule-1 (KIM-1) was persistently elevated in both IRV and IRS rats; however, KIM-1 tissue expression was attenuated in IRS rats. Additionally, sustained loss of Na+,K+-ATPase expression and basolateral localization and elevated vimentin in IRV rats was normalized in IRS rats, suggesting restoration of a differentiated, polarized tubule epithelium. The results suggest that SRT1720 treatment expedited recovery of mitochondrial protein expression and function by enhancing MB, which was associated with faster proximal tubule repair. Targeting MB may offer unique therapeutic strategy following ischemic injury.

show abstract

“…Another important characteristic of AKI is the change in renal sodium excretion [ 38 , 39 ]. Renal sodium handling depends on sodium reabsorption along the nephron, which is directly correlated to (Na + +K + )ATPase activity [ 33 , 34 , 40 , 41 ]. Here, it was observed that PbA-infected mice presented a decrease in urinary sodium excretion ( Fig 5A ).…”

Section: Resultsmentioning

confidence: 99%

The angiotensin II/AT1 receptor pathway mediates malaria-induced acute kidney injury

et al. 2018

View full text Add to dashboard Cite

Malaria-induced acute kidney injury (MAKI) is a life-threatening complication of severe malaria. Here, we investigated the potential role of the angiotensin II (Ang II)/AT1 receptor pathway in the development of MAKI. We used C57BL/6 mice infected by Plasmodium berghei ANKA (PbA-infected mice), a well-known murine model of severe malaria. The animals were treated with 20 mg/kg/day losartan, an antagonist of AT1 receptor, or captopril, an angiotensin-converting enzyme inhibitor. We observed an increase in the levels of plasma creatinine and blood urea nitrogen associated with a significant decrease in creatinine clearance, a marker of glomerular flow rate, and glomerular hypercellularity, indicating glomerular injury. PbA-infected mice also presented proteinuria and a high level of urinary γ-glutamyltransferase activity associated with an increase in collagen deposition and interstitial space, showing tubule-interstitial injury. PbA-infected mice were also found to have increased fractional excretion of sodium (FENa+) coupled with decreased cortical (Na++K+)ATPase activity. These injuries were associated with an increase in pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-6, interleukin-17, and interferon gamma, in the renal cortex of PbA-infected mice. All modifications of these structural, biochemical, and functional parameters observed in PbA-infected mice were avoided with simultaneous treatment with losartan or captopril. Our data allow us to postulate that the Ang II/AT1 receptor pathway mediates an increase in renal pro-inflammatory cytokines, which in turn leads to the glomerular and tubular injuries observed in MAKI.

show abstract

Targeting of renal proximal tubule Na,K-ATPase by salt-inducible kinase

Cited by 35 publications

References 35 publications

Epilepsy-causing sequence variations in SIK1 disrupt synaptic activity response gene expression and affect neuronal morphology

Epilepsy-causing sequence variations in SIK1 disrupt synaptic activity response gene expression and affect neuronal morphology

Accelerated recovery of renal mitochondrial and tubule homeostasis with SIRT1/PGC-1α activation following ischemia–reperfusion injury

The angiotensin II/AT1 receptor pathway mediates malaria-induced acute kidney injury

Contact Info

Product

Resources

About