Angiotensin II stimulation promotes mitochondrial fusion as a novel mechanism involved in protein kinase compartmentalization and cholesterol transport in human adrenocortical cells

Helfenberger, Katia Estefanía; Castillo, Ana Fernanda; Mele, Pablo G.; Fiore, Ana Paula Zen Petisco; Herrera, Lucía Manuela; Finocchietto, Paola; Podestá, Ernesto J.; Poderoso, Cecilia

doi:10.1016/j.jsbmb.2019.105413

Cited by 11 publications

(17 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Generally, both ligands upregulated or downregulated the same pathways (Figure 3A). For example, the hallmark set for cholesterol homeostasis was upregulated by both ligands, consistent with previous reports indicating that stimulation promotes cholesterol biosynthesis, cholesterol ester uptake, and cholesterol transport [32][33][34][35]. Interestingly, adipogenesis and xenobiotic metabolism were enriched by ACTH stimulation, but not by AngII stimulation.…”

Section: Acth-and Angii-regulated Pathways In Primary Adrenocortical Cellssupporting

confidence: 89%

Transcriptomic Response Dynamics of Human Primary and Immortalized Adrenocortical Cells to Steroidogenic Stimuli

Wellman

Baldwin

et al. 2021

Cells

View full text Add to dashboard Cite

Adrenal steroid hormone production is a dynamic process stimulated by adrenocorticotropic hormone (ACTH) and angiotensin II (AngII). These ligands initialize a rapid and robust gene expression response required for steroidogenesis. Here, we compare the predominant human immortalized cell line model, H295R cell, with primary cultures of adult adrenocortical cells derived from human kidney donors. We performed temporally resolved RNA-seq on primary cells stimulated with either ACTH or AngII at multiple time points. The magnitude of the expression dynamics elicited by ACTH was greater than AngII in primary cells. This is likely due to the larger population of adrenocortical cells that are responsive to ACTH. The dynamics of stimulus-induced expression in H295R cells are mostly recapitulated in primary cells. However, there are some expression responses in primary cells absent in H295R cells. These data are a resource for the endocrine community and will help researchers determine whether H295R is an appropriate model for the specific aspect of steroidogenesis that they are studying.

show abstract

Section: Acth-and Angii-regulated Pathways In Primary Adrenocortical Cellssupporting

confidence: 89%

Transcriptomic Response Dynamics of Human Primary and Immortalized Adrenocortical Cells to Steroidogenic Stimuli

Wellman

Baldwin

et al. 2021

Cells

View full text Add to dashboard Cite

show abstract

“…Mitochondrial dynamics are implicated not only in maintaining the equilibrium of organelles by repairing or eliminating defective mitochondria [31], but also in regulating steroidogenesis [32]. Accordingly, Ang II was demonstrated to promote aldosterone synthesis in H295 cells by increasing fusion of mitochondria and translocation in these organelles of relevant steroidogenic proteins, such as STAR, that is responsible for cholesterol transport from the outer to the inner mitochondrial membrane, and protein kinase C (PKC) ε, mitogen-activated protein kinase (MEK) and ERK, that drive the activation signaling in mitochondria [33]. Whether and how this occurs in APA, where, as mentioned above, Ang II is low, remains to be investigated [11].…”

Section: Effects Of Ang II On the Mitochondria Functionmentioning

confidence: 99%

Angiotensin peptides in the regulation of adrenal cortical function

Rossi¹,

Lenzini

Caroccia

et al. 2021

Exploration of Medicine

View full text Add to dashboard Cite

The adrenal cortex plays a key role in the regulation of metabolism, salt and water homeostasis and sex differentiation by synthesizing glucocorticoid, mineralocorticoid and androgen hormones. Evidence exists that angiotensin II regulates adrenocortical function and it has been contended that angiotensin peptides of the non-canonical branch of the renin angiotensin system (RAS) might also modulate steroidogenesis in adrenals. Thus, the aim of this review is to examine the role of the RAS, and particularly of the angiotensin peptides and their receptors, in the regulation of adrenocortical hormones with particular focus on aldosterone production.

show abstract

“…Previous studies have shown that abnormal mitochondrial dynamics can induce abnormal ROS release from mitochondria and cell apoptosis. Several studies have indicated that Ang II can promote apoptosis through mitochondrial fission in a Drp1‐dependent manner 14–16 …”

Section: Introductionmentioning

confidence: 99%

“…Several studies have indicated that Ang II can promote apoptosis through mitochondrial fission in a Drp1‐dependent manner. 14 , 15 , 16 …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sirt6 deficiency contributes to mitochondrial fission and oxidative damage in podocytes via ROCK1‐Drp1 signalling pathway

Chen

Liang

et al. 2022

Cell Proliferation

View full text Add to dashboard Cite

Objectives: Increasing evidence suggests that mitochondrial dysfunction is the key driver of angiotensin II (Ang II)-induced kidney injury. This study was designed to investigate whether Sirtuin 6 (Sirt6) could affect Ang II-induced mitochondrial damage and the potential mechanisms.Materials and Methods: Podocyte-specific Sirt6 knockout mice were infused with Ang II and cultured podocytes were stimulated with Ang II to evaluate the effects of Sirt6 on mitochondrial structure and function in podocytes. Immunofluorescence staining was used to detect protein expression and mitochondrial morphology in vitro. Electron microscopy was used to assess mitochondrial morphology in mice.Western blotting was used to quantify protein expression.Results: Mitochondrial fission and decreased Sirt6 expression were observed in podocytes from Ang II-infused mice. In Sirt6-deficient mice, Ang II infusion induced increased apoptosis and mitochondrial fragmentation in podocytes than that in Ang II-infused wild-type mice. In cultured human podocytes, Sirt6 knockdown exacerbated Ang II-induced mitochondrial fission, whereas Sirt6 overexpression ameliorated the Ang II-induced changes in the balance between mitochondrial fusion and fission.Functional studies revealed that Sirt6 deficiency exacerbated mitochondrial fission by promoting dynamin-related protein 1 (Drp1) phosphorylation. Furthermore, Sirt6 mediated Drp1 phosphorylation by promoting Rho-associated coiled coil-containing protein kinase 1 (ROCK1) expression. Conclusion:Our study has identified Sirt6 as a vital factor that protects against Ang II-induced mitochondrial fission and apoptosis in podocytes via the ROCK1-Drp1 signalling pathway. | INTRODUCTIONThe renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in the occurrence and progression of chronic kidney diseases (CKD). 1 Zhaowei Chen and Wei Liang contributed equally to this work.

show abstract

Angiotensin II stimulation promotes mitochondrial fusion as a novel mechanism involved in protein kinase compartmentalization and cholesterol transport in human adrenocortical cells

Abstract: stimulation promotes mitochondrial fusion as a novel mechanism involved in protein kinase compartmentalization and cholesterol transport in human adrenocortical cells,

Cited by 11 publications

References 79 publications

Transcriptomic Response Dynamics of Human Primary and Immortalized Adrenocortical Cells to Steroidogenic Stimuli

Transcriptomic Response Dynamics of Human Primary and Immortalized Adrenocortical Cells to Steroidogenic Stimuli

Angiotensin peptides in the regulation of adrenal cortical function

Sirt6 deficiency contributes to mitochondrial fission and oxidative damage in podocytes via ROCK1‐Drp1 signalling pathway

Contact Info

Product

Resources

About