Anti-necrotic and cardioprotective effects of a cytosolic renin isoform under ischemia-related conditions

Wanka, Heike; Staar, Doreen; Lutze, Philipp; Peters, Barbara; Hildebrandt, Johanna; Beck, Tim; Bäumgen, Inga; Albers, Alexander; Krieg, Thomas; Zimmermann, Katrin; Sczodrok, Jaroslaw; Schäfer, Simon; Hoffmann, Sigrid; Peters, Jörg

doi:10.1007/s00109-015-1321-z

Cited by 19 publications

(47 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For PCR and functional analyses, cells were seeded in culture plates (Greiner bio-one, Frickenhausen, Germany) for 3 days. They were then exposed to siRNA-mediated SRF knock down followed by glucose depletion for another 24 hours as described previously [12]. …”

Section: Methodsmentioning

confidence: 99%

An Alternative Promoter in Intron1 of the Renin Gene is Regulated by Glucose Starvation via Serum Response Factor

Lutze¹,

Wanka²,

Bäumgen³

et al. 2017

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background/Aims: Renin is known as a secretory glycoprotein that ultimately leads to angiotensin II generation. In this way renin exerts pro-inflammatory effects and promotes cardiac injury. Additional transcripts have been identified encoding for a cytosolic renin isoform that - in contrast to secretory renin - exhibits cardioprotective effects under ischemic conditions. The promoter of these transcripts is unknown. Methods: Using qRT-PCR and dual-luciferase reporter assay we examined the expression and promotor activity of cytosolic renin as well as the regulation by glucose starvation in H9c2 cardiomyoblasts. Results: We identified a promoter in intron1 of the rat renin gene with two glucose starvation-sensitive regions. One region contains a binding motif for serum response factor (SRF). Under glucose depletion expression of SRF increased prior to cytosolic renin. SRF knock down selectively decreased cytosolic renin expression and attenuated the increase of cytosolic renin expression under glucose depletion. Conclusions: Transcripts encoding for secretory and cytosolic renin are differentially expressed. The low basal expression of cytosolic renin as well as its induction under ischemia-related conditions represents an efficient system regulated in accordance with its previously identified unfavorable effects under control situations but protective effects seen after myocardial infarction or glucose depletion.

show abstract

Section: Methodsmentioning

confidence: 99%

An Alternative Promoter in Intron1 of the Renin Gene is Regulated by Glucose Starvation via Serum Response Factor

Lutze¹,

Wanka²,

Bäumgen³

et al. 2017

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, as the aim of the study was to investigate the so far unknown functions of cyto‐renin, we deem H9c2 cell line to be an appropriate model. Moreover, with respect to the protective effects of cyto‐renin we already demonstrated such effects also in primary adult cardiomyocytes as well as in the isolated perfused heart preparations …”

Section: Discussionmentioning

confidence: 69%

“…This promoter has very low basal activity, but is stimulated by glucose depletion in cardiac cells as well as after myocardial infarction in the rat heart . Cells overexpressing cyto‐renin are more resistant against necrotic death under ischaemic conditions such as glucose depletion . Moreover, overexpression of cyto‐renin in the heart of transgenic rats reduces infarct size in ex vivo Langendorff preparations …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An alternative renin isoform is cardioprotective by modulating mitochondrial metabolism

Wanka

Lutze

Staar

et al. 2018

J Cellular Molecular Medi

Self Cite

View full text Add to dashboard Cite

The renin‐angiotensin system promotes oxidative stress, apoptosis, necrosis, fibrosis, and thus heart failure. Secretory renin plays a central role in these processes, initiating the generation of angiotensins. Nevertheless, alternative renin transcripts exist, which code for a cytosolically localized renin isoform (cyto‐renin) that is cardioprotective. We tested the hypothesis that the protective effects are associated with a beneficial switch of metabolic and mitochondrial functions. To assess H9c2 cell mitochondrial parameters, we used the Seahorse XF analyser. Cardiac H9c2 cells overexpressing cyto‐renin exhibited enhanced nonmitochondrial oxygen consumption, lactate accumulation, and LDH activity, reflecting a switch to more aerobic glycolysis known as Warburg effect. Additionally, mitochondrial spare capacity and cell respiratory control ratio were enhanced, indicating an increased potential to tolerate stress conditions. Renin knockdown induced opposite effects on mitochondrial functions without influencing metabolic parameters. Thus, the protective effects of cyto‐renin are associated with an altered bioenergetic profile and an enhanced stress tolerance, which are favourable under ischaemic conditions. Therefore, cyto‐renin is a promising new target for the prevention of ischaemia‐induced myocardial damage.

show abstract

“…Peters and colleagues find that truncated renin specifically localized to the mitochondria and that the active form of renin, but not prorenin, was internalized by mitochondria [14,18,19]. The overexpression of the active renin isoform protected the cells under high glucose conditions and this effect was not reversed by the renin inhibitor aliskerin or an AT 1 R antagonist suggesting that the beneficial effects may not reflect activation of the Ang II-AT 1 R axis [20]. In support of these findings, we recently reported the presence of active renin in isolated mitochondria from the sheep renal cortex [21].…”

Section: Reninmentioning

confidence: 99%

Peptidases and the Renin-Angiotensin System: The Alternative Angiotensin-(1-7) Cascade

Cruz‐Diaz¹,

Wilson²,

Chappell³

2017

Enzyme Inhibitors and Activators

View full text Add to dashboard Cite

The renin-angiotensin system (RAS) constitutes a key hormonal system in the physiological regulation of blood pressure via peripheral and central mechanisms. Dysregulation of the RAS is considered a major factor in the development of cardiovascular pathologies, and pharmacologic blockades of this system by the inhibition of angiotensin-converting enzyme (ACE) or antagonism of the angiotensin type 1 receptor (AT 1 R) are effective therapeutic regimens. The RAS is now defined as a system composed of different angiotensin peptides with diverse biological actions mediated by distinct receptor subtypes. The classic RAS comprises the ACE-Ang II-AT 1 R axis that promotes vasoconstriction, water intake, sodium retention and increased oxidative stress, fibrosis, cellular growth, and inflammation. The nonclassical or alternative RAS is composed primarily of the ACE2-Ang-(1-7)-AT 7 R pathway that opposes the Ang II-AT 1 R axis. In lieu of the complex aspects of this system, the current review assesses the enzymatic cascade of the alternative Ang-(1-7) axis of the RAS.

show abstract

Anti-necrotic and cardioprotective effects of a cytosolic renin isoform under ischemia-related conditions

Cited by 19 publications

References 38 publications

An Alternative Promoter in Intron1 of the Renin Gene is Regulated by Glucose Starvation via Serum Response Factor

An Alternative Promoter in Intron1 of the Renin Gene is Regulated by Glucose Starvation via Serum Response Factor

An alternative renin isoform is cardioprotective by modulating mitochondrial metabolism

Peptidases and the Renin-Angiotensin System: The Alternative Angiotensin-(1-7) Cascade

Contact Info

Product

Resources

About