Mitochondrial Lon protease controls ROS-dependent apoptosis in cardiomyocyte under hypoxia

Kuo, Chan‐Yen; Chiu, Yi-Chieh; Lee, Alan Yueh‐Luen; Hwang, Tsong‐Long

doi:10.1016/j.mito.2015.04.004

Cited by 65 publications

(44 citation statements)

References 35 publications

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“…Cardiomyocyte apoptosis induced by I/R is an essential process in the progression of heart failure. Mitochondria play a crucial role in cardiomyocyte apoptosis under hypoxic conditions [3,4]. This study showed that H/R treatment caused mitochondrial dysfunction and cardiomyocyte apoptosis, whereas, pretreatment with geniposide improved mitochondrial dysfunction and attenuated mitochondria-dependent cell apoptosis.…”

Section: Discussionmentioning

confidence: 75%

“…ROS and RNS are products of mitochondrial oxidative stress, and production of ROS is a vital step in the mitochondria-dependent apoptosis pathway [3,4,27]. Physiological levels of ROS/RNS in normal oxidative metabolism play a key homeostatic role in balancing disposal rates of oxidative pressure and enzyme systems in cell proliferation and survival [27][28][29].…”

Section: Discussionmentioning

confidence: 99%

“…Cardiomyocyte apoptosis caused by ischemia/reperfusion (I/R) injury can lead to myocardial cell loss, which further accelerates cardiac dysfunction, ventricular remodeling, and even heart failure [3][4][5][6]. Numerous studies have reported that inhibition of apoptosis could attenuate myocardial damage, decrease cardiomyocyte removal, and improve ventricular contractile function caused by I/R [7].…”

Section: Introductionmentioning

confidence: 99%

“…Cardiomyocyte apoptosis includes two major pathways, the extrinsic pathway via death receptors, and the intrinsic pathway involving mitochondria [8,9]. Notably, the mitochondria-dependent pathway plays a key role in I/R-induced myocardial cell apoptosis [3,4,10]. The most typical characteristic of myocardial ischemia is severe hypoxia, which could cause acidosis, energy depletion, and ion homeostasis rupture, ultimately resulting in cardiomyocyte death [11].…”

Section: Introductionmentioning

confidence: 99%

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Geniposide Prevents Hypoxia/Reoxygenation-Induced Apoptosis in H9c2 Cells: Improvement of Mitochondrial Dysfunction and Activation of GLP-1R and the PI3K/AKT Signaling Pathway

Jiang

Chang²,

Wang³

et al. 2016

Cell Physiol Biochem

104

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Background/Aims: Myocardial ischemia/reperfusion injury is a major cause of morbidity and mortality associated with coronary heart disease. Many studies have demonstrated that natural products are promising chemotherapeutic drugs counteracting the loss of cardiomyocytes. Thus, the purpose of the present study was to investigate the effects of geniposide, a traditional Chinese herb extract from Gardenia jasminoides J. Ellis, on cardiomyocyte apoptosis induced by hypoxia/reoxygenation (H/R) in H9c2 cells, and their underlying mechanisms. Methods: Cell viability and apoptosis ratio were assessed using the cell counting kit-8 assay and Annexin V/propidium iodide (PI) staining. The concentrations of lactate dehydrogenase (LDH), intracellular total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were detected by microplate reader. The production of reactive oxygen species/reactive nitrogen species (ROS/RNS), the level of mitochondrial calcium, and mitochondrial membrane potential depolarization were measured by confocal laser scanning microscopy. Mitochondrial morphology was visualized using transmission electron microscopy. The expressions of Bcl-2 mRNA and Caspase-3 mRNA were measured by reverse transcription-polymerase chain reaction (RT-PCR). The protein levels of cleaved caspase-3, Bcl-2, Bax, AKT, p-AKT^serine473, cytochrome-c were detected by western bloting. Results: Geniposide pretreatment increased cell viability, decreased LDH levels in the supernatant, and inhibited cardiomyocyte apoptosis caused by H/R. Furthermore, geniposide reversed mitochondrial dysfunction by decreasing oxidative stress products (ROS/RNS and MDA), increasing anti-oxidative enzyme (T-SOD) level, improving mitochondrial morphology, attenuating mitochondrial calcium overload and blunting depolarization of mitochondrial membrane. Moreover, geniposide pretreatment increased Bcl-2 level and decreased Bax level, thus enhancing the Bcl-2/Bax ratio. Consistent with the above result, Bcl-2 mRNA expression was upregulated and caspase-3 mRNA expression was downregulated by geniposide. In addition, geniposide decreased the protein expression of cleaved caspase-3 and cytochrome-c and increased the level p-AKT^serine473. The protective effects of geniposide were partially reversed by glucagon-like pepitide-1 receptor antagonist exendin-(9-39) and the phosphatidylinositol 3 kinase (PI3K) inhibitor LY294002. Conclusions: Our results suggest that geniposide pretreatment inhibits H/R-induced myocardial apoptosis by reversing mitochondrial dysfunction, an effect in part due to activation of GLP-1R and PI3K/AKT signaling pathway.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Geniposide Prevents Hypoxia/Reoxygenation-Induced Apoptosis in H9c2 Cells: Improvement of Mitochondrial Dysfunction and Activation of GLP-1R and the PI3K/AKT Signaling Pathway

Jiang

Chang²,

Wang³

et al. 2016

Cell Physiol Biochem

104

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show abstract

“…Although our prior studies proved that TXL had infarct-sparing effect during I/R in animals, it remained unclear whether TXL could protect human cardiomyocytes from reperfusion injury. As a consequence, for our in vitro experiments, we used human cardiomyocytes, which are widely employed in cardiovascular research (Albrecht-Schgoer et al, 2012;Boon et al, 2013;Baker et al, 2015;Kuo et al, 2015;Nehra et al, 2015;Sharma et al, 2015), rather than cardiomyocytes isolated from animals.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Mir-128-3p by Tongxinluo Protects Human Cardiomyocytes From Ischemia/Reperfusion Injury via Upregulation of P70s6k1/P-P70s6k1

Chen

Yang

et al. 2018

Journal of the American College of Cardiology

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Mitochondria‐specific antioxidant MitoTEMPO alleviates senescence of bone marrow mesenchymal stem cells in ovariectomized rats

Li,

Zhang,

Zhang

et al. 2024

Journal Cellular Physiology

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Senescence in bone marrow mesenchymal stem cells (BMSCs), triggered by excessive oxidative stress, plays a crucial role in the onset of postmenopausal osteoporosis. Recent studies underscore the importance of mitochondrial rehabilitation and quality control as key determinants in the modulation of oxidative stress and cellular senescence. MitoTEMPO, a mitochondria‐targeted antioxidant, has been shown to mitigate the heightened levels of reactive oxygen species (ROS). In our research, we observed that BMSCs from ovariectomized (OVX) rats displayed premature senescence, which was attributed to combined mitochondrial and lysosomal dysfunction, a condition that worsens with extended estrogen deprivation. Treatment with MitoTEMPO effectively reversed these effects, reinstating lysosomal functionality and suppressing the mitochondrial unfolded protein response (UPRmt). Subsequent in vivo experiments corroborated these observations, revealing that MitoTEMPO administration in OVX rats curtailed trabecular bone loss and reduced the expression of p53, HSP60, and CLPP in the trabecular bone region of the proximal tibia. Overall, our findings suggest that MitoTEMPO holds promise as a therapeutic agent to counteract senescence in OVX‐BMSCs, offering a potential strategy for treating postmenopausal osteoporosis.

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Mitochondrial Lon protease controls ROS-dependent apoptosis in cardiomyocyte under hypoxia

Cited by 65 publications

References 35 publications

Geniposide Prevents Hypoxia/Reoxygenation-Induced Apoptosis in H9c2 Cells: Improvement of Mitochondrial Dysfunction and Activation of GLP-1R and the PI3K/AKT Signaling Pathway

Geniposide Prevents Hypoxia/Reoxygenation-Induced Apoptosis in H9c2 Cells: Improvement of Mitochondrial Dysfunction and Activation of GLP-1R and the PI3K/AKT Signaling Pathway

Inhibition of Mir-128-3p by Tongxinluo Protects Human Cardiomyocytes From Ischemia/Reperfusion Injury via Upregulation of P70s6k1/P-P70s6k1

Mitochondria‐specific antioxidant MitoTEMPO alleviates senescence of bone marrow mesenchymal stem cells in ovariectomized rats

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