Changes in mitochondrial functionality and calcium uptake in hypertensive rats as a function of age

Calderón-Cortés, Elizabeth; Cortés‐Rojo, Christian; Clemente‐Guerrero, Mónica; Manzo‐Ávalos, Salvador; Villalobos‐Molina, Rafael; Boldogh, István; Saavedra‐Molina, Alfredo

doi:10.1016/j.mito.2008.04.005

Cited by 17 publications

(16 citation statements)

References 36 publications

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“…Cotransfection of MnSOD with eNOS prevented the rebound in ABP induced by eNOS overexpression in the SHR. Other studies reported an alteration in mCa 2þ handling in brain mitochondria during hypertension (89). These studies demonstrate the contribution of RNS, ROS, and mCa 2þ in regulating ABP through their actions on ETC complexes.…”

Section: Mitochondria and Hypertensionsupporting

confidence: 69%

Potential Therapeutic Benefits of Strategies Directed to Mitochondria

Camara

Lesnefsky

Stowe

2010

Antioxidants & Redox Signaling

165

226

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The mitochondrion is the most important organelle in determining continued cell survival and cell death. Mitochondrial dysfunction leads to many human maladies, including cardiovascular diseases, neurodegenerative disease, and cancer. These mitochondria-related pathologies range from early infancy to senescence. The central premise of this review is that if mitochondrial abnormalities contribute to the pathological state, alleviating the mitochondrial dysfunction would contribute to attenuating the severity or progression of the disease. Therefore, this review will examine the role of mitochondria in the etiology and progression of several diseases and explore potential therapeutic benefits of targeting mitochondria in mitigating the disease processes. Indeed, recent advances in mitochondrial biology have led to selective targeting of drugs designed to modulate and manipulate mitochondrial function and genomics for therapeutic benefit. These approaches to treat mitochondrial dysfunction rationally could lead to selective protection of cells in different tissues and various disease states. However, most of these approaches are in their infancy.

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Section: Mitochondria and Hypertensionsupporting

confidence: 69%

Potential Therapeutic Benefits of Strategies Directed to Mitochondria

Camara

Lesnefsky

Stowe

2010

Antioxidants & Redox Signaling

165

226

View full text Add to dashboard Cite

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“…Various studies have suggested that mitochondrial Ca 2ϩ handling is disrupted by aging that could contribute to cell death because mitochondria play an important role buffering cytosolic Ca 2ϩ concentration (4,36,46). Importantly, reduced mitochondrial Ca 2ϩ uptake in aging may contribute to subsequent tissue injury.…”

Section: Tempol Effects On Mitochondria [Ca 2ϩ ] M Uptakementioning

confidence: 99%

Chronic Tempol treatment restores pharmacological preconditioning in the senescent rat heart

Zhu

Rebecchi

Wang

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…Generally, mitochondrial matrix Ca 2+ can activate PDH at its E1α subunit and promote the transformation of pyruvic acid to acetyl‐CoA in the mitochondrial matrix . PDH is a key dehydrogenase, and its activity can also be blunted by angiotensin II through increasing the vascular PDH phosphorylation . However, the regulation of PDH activities in the vasculature in hypertension is poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, TRPC3 channel protein has been shown to localize in the inner membrane of mitochondria and to regulate mitochondrial Ca 2+ uptake . Other groups have investigated that the basal [Ca 2+ ] mito levels were different in heart, kidney, and brain tissues from SHRs compared with WKY rats, but the differences and functions of [Ca 2+ ] mito in the vasculature of SHRs remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Mitochondrial Transient Receptor Potential Channel, Canonical Type 3–Mediated Calcium Handling in the Vasculature From Hypertensive Rats

Wang

Xiong

Lin

et al. 2017

JAHA

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BackgroundMitochondrial Ca2+ homeostasis is fundamental to the regulation of mitochondrial reactive oxygen species (ROS) generation and adenosine triphosphate production. Recently, transient receptor potential channel, canonical type 3 (TRPC3), has been shown to localize to the mitochondria and to play a role in maintaining mitochondrial calcium homeostasis. Inhibition of TRPC3 attenuates vascular calcium influx in spontaneously hypertensive rats (SHRs). However, it remains elusive whether mitochondrial TRPC3 participates in hypertension by increasing mitochondrial calcium handling and ROS production.Methods and ResultsIn this study we demonstrated increased TRPC3 expression in purified mitochondria in the vasculature from SHRs, which facilitates enhanced mitochondrial calcium uptake and ROS generation compared with Wistar‐Kyoto rats. Furthermore, inhibition of TRPC3 by its specific inhibitor, Pyr3, significantly decreased the vascular mitochondrial ROS production and H2O2 synthesis and increased adenosine triphosphate content. Administration of telmisartan can improve these abnormalities. This beneficial effect was associated with improvement of the mitochondrial respiratory function through recovering the activity of pyruvate dehydrogenase in the vasculature of SHRs. In vivo, chronic administration of telmisartan suppressed TRPC3‐mediated excessive mitochondrial ROS generation and vasoconstriction in the vasculature of SHRs. More importantly, TRPC3 knockout mice exhibited significantly ameliorated hypertension through reduction of angiotensin II–induced mitochondrial ROS generation.ConclusionsTogether, we give experimental evidence for a potential mechanism by which enhanced TRPC3 activity at the cytoplasmic and mitochondrial levels contributes to redox signaling and calcium dysregulation in the vasculature from SHRs. Angiotensin II or telmisartan can regulate [Ca2+]mito, ROS production, and mitochondrial energy metabolism through targeting TRPC3.

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Changes in mitochondrial functionality and calcium uptake in hypertensive rats as a function of age

Cited by 17 publications

References 36 publications

Potential Therapeutic Benefits of Strategies Directed to Mitochondria

Potential Therapeutic Benefits of Strategies Directed to Mitochondria

Chronic Tempol treatment restores pharmacological preconditioning in the senescent rat heart

Enhanced Mitochondrial Transient Receptor Potential Channel, Canonical Type 3–Mediated Calcium Handling in the Vasculature From Hypertensive Rats

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