Effects of Telmisartan, an AT1 receptor antagonist, on mitochondria-specific genes expression in a mouse MPTP model of Parkinsonism

Ray, Bipul; Ramesh, Girish; Verma, Sudhir Rama; Ramamurthy, Srinivasan; Tuladhar, Sunanda; Mahalakshmi, Arehally M.; Essa, Musthafa Mohamed; Chidambaram, Saravana Babu

doi:10.52586/4942

Cited by 6 publications

(4 citation statements)

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“…A recent animal study showed that AT 1 and AT 2 form AT1/2 heterodimers, which are expressed in both striatal neurons and microglia in the central nervous system ( Rivas-Santisteban et al, 2020 ). Moreover, some experimental studies on the effects of telmisartan and candesartan, which are typical ARBs known to penetrate the BBB, showed an improvement in dopaminergic and mitochondrial functions in an animal PD model ( Sekar et al, 2018 ; Ray et al, 2021 ). Previous clinical studies on dementia also showed that BBB-crossing RAS inhibitors have better neuroprotective effects than non-BBB-crossing agents ( Ho et al, 2021 ; Ouk et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…These two receptors are present in various tissues, including the brain ( Rivas-Santisteban et al, 2020 ). Recent evidence from animal studies showed that inhibition of brain RAS is associated with decreased dopaminergic neuronal loss and reduced oxidative stress in PD via the via alleviation of mitochondrial function ( Perez-Lloret et al, 2017 ; Ray et al, 2021 ). Brain RAS blockade may play a protective role in neuroinflammation and accumulation of phosphorylated alpha-synuclein.…”

Section: Introductionmentioning

confidence: 99%

“…Brain RAS blockade may play a protective role in neuroinflammation and accumulation of phosphorylated alpha-synuclein. This is accomplished by blocking the Ang II-related pro-inflammatory oxidative effects and reducing the production of reactive oxygen species associated with AT 1 receptor overexpression in the substantia nigra ( Wright and Harding, 2012 ; Perez-Lloret et al, 2017 ; Ray et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Protective Effect of Renin-Angiotensin System Inhibitors on Parkinson’s Disease: A Nationwide Cohort Study

Kim

et al. 2022

Front. Pharmacol.

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Background: Renin-angiotensin system (RAS) inhibitors have been suggested as protective agents in Parkinson’s disease (PD). However, epidemiological evidence on the association between RAS inhibitors and the development of PD is inconsistent.Objectives: To investigate the effect of RAS inhibitors on PD risk in patients with ischemic heart disease (IHD) by type and cumulative duration of RAS inhibitors and their degree of blood-brain barrier (BBB) penetration ability.Methods: This was a propensity score-matched retrospective cohort study using 2008–2019 healthcare claims data from the Korean Health Insurance Review and Assessment database. The association between RAS inhibitor use and PD in patients with IHD was evaluated using multivariate Cox proportional hazard regression analysis. The risks are presented as adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).Results: Over a 10-year follow-up, 1,086 of 62,228 IHD patients developed PD. The Cox regression model showed that the use of RAS inhibitors was significantly associated with a lower risk of PD (aHR = 0.75; 95% CI 0.66–0.85) than the non-use of RAS inhibitors. Specifically, this reduced risk of PD only remained with the use of BBB-crossing angiotensin II receptor blockers (ARBs) (aHR = 0.62; 95% CI = 0.53–0.74), and this association was more definite with an increasing cumulative duration. A significantly reduced risk of PD was not observed with the use of BBB-crossing angiotensin-converting enzyme inhibitors.Conclusions: The use of ARBs with BBB-penetrating properties and a high cumulative duration significantly reduces the risk of PD in IHD patients. This protective effect could provide insight into disease-modifying drug candidates for PD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Protective Effect of Renin-Angiotensin System Inhibitors on Parkinson’s Disease: A Nationwide Cohort Study

Kim

et al. 2022

Front. Pharmacol.

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“…Recently, in a mouse model of Parkinsonism, telmisartan was demonstrated to improve mitochondrial functions by upregulating mitochondria-specific genes expression [ 64 ]. In addition, in renal glomerular endothelial cells, telmisartan elicited a protective effect against high-glucose-induced injury by ameliorating mitochondrial dysfunction and oxidative stress, as evidenced by the increased mitochondrial membrane potential and the reduced levels of 8-hydroxy-2 deoxyguanosine (8-OHDG) and malondialdehyde [ 65 ].…”

Section: Mitochondrial Effects Of the Main Classes Of Drugs Used In C...mentioning

confidence: 99%

Mitochondrial Effects of Common Cardiovascular Medications: The Good, the Bad and the Mixed

Bețiu

Noveanu

Hâncu

et al. 2022

IJMS

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Mitochondria are central organelles in the homeostasis of the cardiovascular system via the integration of several physiological processes, such as ATP generation via oxidative phosphorylation, synthesis/exchange of metabolites, calcium sequestration, reactive oxygen species (ROS) production/buffering and control of cellular survival/death. Mitochondrial impairment has been widely recognized as a central pathomechanism of almost all cardiovascular diseases, rendering these organelles important therapeutic targets. Mitochondrial dysfunction has been reported to occur in the setting of drug-induced toxicity in several tissues and organs, including the heart. Members of the drug classes currently used in the therapeutics of cardiovascular pathologies have been reported to both support and undermine mitochondrial function. For the latter case, mitochondrial toxicity is the consequence of drug interference (direct or off-target effects) with mitochondrial respiration/energy conversion, DNA replication, ROS production and detoxification, cell death signaling and mitochondrial dynamics. The present narrative review aims to summarize the beneficial and deleterious mitochondrial effects of common cardiovascular medications as described in various experimental models and identify those for which evidence for both types of effects is available in the literature.

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Metastasis‐associated 1 localizes to the sarcomeric Z‐disc and is implicated in skeletal muscle pathology

Xue,

Han,

Sun

et al. 2024

Cytoskeleton

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Metastasis‐associated 1 (MTA1), a subunit of the nucleosome remodeling and histone deacetylation (NuRD) corepressor complex, was reported to be expressed in the cytoplasm of skeletal muscles. However, the exact subcellular localization and the functional implications of MTA1 in skeletal muscles have not been examined. This study aims to demonstrate the subcellular localization of MTA1 in skeletal muscles and reveal its possible roles in skeletal muscle pathogenesis. Striated muscles (skeletal and cardiac) from C57BL/6 mice of 4–5 weeks were collected to examine the expression of MTA1 by Western blotting and immunohistochemistry. Immunofluorescence and immunoelectron microscopy were performed for MTA1, α‐actinin (a Z‐disc marker protein), and SMN (survival of motor neuron) proteins. Gene Expression Omnibus (GEO) data sets were analyzed using the GEO2R online tool to explore the functional implications of MTA1 in skeletal muscles. MTA1 expression was detected by Western blotting and immunohistochemistry in skeletal and cardiac muscles. Subcellular localization of MTA1 was found in the Z‐disc of sarcomeres, where α‐actinin and SMN were expressed. Data mining of GEO profiles suggested that MTA1 dysregulation is associated with multiple skeletal muscle defects, such as Duchenne muscular dystrophy, Emery‐Dreifuss muscular dystrophy, nemaline myopathy, and dermatomyositis. The GEO analysis also showed that MTA1 expression gradually decreased with age in mouse skeletal muscle precursor cells. The subcellular localization of MTA1 in sarcomeres of skeletal muscles implies its biological roles in sarcomere structures and its possible contribution to skeletal muscle pathology.

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Effects of Telmisartan, an AT1 receptor antagonist, on mitochondria-specific genes expression in a mouse MPTP model of Parkinsonism

Cited by 6 publications

References 44 publications

Protective Effect of Renin-Angiotensin System Inhibitors on Parkinson’s Disease: A Nationwide Cohort Study

Protective Effect of Renin-Angiotensin System Inhibitors on Parkinson’s Disease: A Nationwide Cohort Study

Mitochondrial Effects of Common Cardiovascular Medications: The Good, the Bad and the Mixed

Metastasis‐associated 1 localizes to the sarcomeric Z‐disc and is implicated in skeletal muscle pathology

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