The key role of PGC-1α in mitochondrial biogenesis and the proliferation of pulmonary artery vascular smooth muscle cells at an early stage of hypoxic exposure

Rao, Jingjing; Li, Jing; Liu, Yun; Lü, Ping; Sun, Xiaochun; Sugumaran, Praveen Kumar; Zhu, Daling

doi:10.1007/s11010-012-1313-z

Cited by 17 publications

(12 citation statements)

References 29 publications

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“…5). Rao et al reported that hypoxia could significantly enhance mitochondrial biogenesis and therefore increase the number of mitochondria [44]. Bonnet et al indicated that hypoxia sensitivity in fawn hooded rats could engender an increased number of mitochondria in PASMCs [45].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Protects Against Pulmonary Arterial Hypertension in Rats via Activation of Silent Information Regulator 1

Jia

et al. 2017

Cell Physiol Biochem

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Background/Objectives: The polyphenol resveratrol (Rev) has been found to exhibit various beneficial effects including prevention of pulmonary arterial hypertension (PAH). The present study was designed to investigate the action and potential mechanism of Rev on PAH, focusing on the role of SIRT1 (Silent Information Regulator 1) in apoptosis of pulmonary artery smooth muscle cells (PASMCs). Methods: PAH rats were established by exposure to hypoxia for 21 days. Rev and SRT1720 (a selective SIRT1 activator) were used to reverse PAH by gavaging rats. PASMCs were confronted with hypoxia for 24 h or 48 h and were then treated with Rev or SRT1720 in vitro. Western blot was performed to detect the protein expression of SIRT1. CCK-8 and scratch wound experiments were carried out to verify cell proliferation. In addition, the TUNEL positive assay and flow cytometry assay were used to measure PASMC apoptosis. Mitochondrial permeability transition (mPT) was identified by confocal microscopy. Right ventricular systolic pressure (RVSP) was determined with a Gould pressure transducer, and right ventricular hypertrophy (RVH) was determined by weighing the cardiac muscle. Results: We demonstrated that Rev could reverse the remodelling of the pulmonary vasculature, thus contributing to alleviating the severity of PAH. Down-regulation of SIRT1 was observed in PAH, but administration of Rev had no obvious effect on the protein expression of SIRT1. In addition, Rev could induce mitochondrial swelling and nuclear pyknosis, leading to small, dense, and dysmorphic mitochondria in rats exposed to hypoxia alone. Rev treatment inhibited PASMC proliferation in a dose-dependent manner in vitro. Incubation with SRT1720, a specific activator of SIRT1, significantly retarded PASMC proliferation and promoted PASMC apoptosis in vitro. The mechanism could be associated with inducing mPT damage in PASMCs. Rev and SRT1720 treatment mitigated RVSP and reduced RVH. Conclusion: Rev produced a beneficial effect partially by enhancing the activation of SIRT1, thus improving RVSP and reducing RVH. SIRT1 activation increased PASMC apoptosis by inducing mPT dysfunction, which might be a novel future strategy for the treatment of PAH.

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Section: Discussionmentioning

confidence: 99%

Resveratrol Protects Against Pulmonary Arterial Hypertension in Rats via Activation of Silent Information Regulator 1

Jia

et al. 2017

Cell Physiol Biochem

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“…In previous research we had observed that PGC-1˛ was evoked by inadequate oxygen in pulmonary artery smooth muscle cells (Rao et al, 2012). To further test whether hypoxia affects PGC-1˛ in PAECs, Western blot and immunochemistry analysis were performed.…”

Section: Pgc-1˛ Expression Increases Under Hypoxia In Cultured Paecsmentioning

confidence: 99%

“…Recent findings have demonstrated elevated PGC-1˛ expression in PAH patients, and proved the necessity of PGC-1˛ in pulmonary artery smooth muscle cells during hypoxia (Mata et al, 2012;Rao et al, 2012). As there are few reports evaluating PGC-1˛ in hypoxic PAECs, we first pay attention to investigate this issue.…”

Section: Introductionmentioning

confidence: 99%

PGC-1α plays a major role in the anti-apoptotic effect of 15-HETE in pulmonary artery endothelial cells

Li¹,

Zhang²,

Liu³

et al. 2015

Respiratory Physiology & Neurobiology

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“…In particular, PGC-1α regulates oxidative phosphorylation, mitochondrial biogenesis and respiration (22,23). Numerous previous studies have suggested that ischemia and hypoxia significantly induce the expression of PGC-1α (5)(6)(7)(8)(9)(10)(11)24,25). Arany et al (12) reported that PGC-1α was able to upregulate the expression of angiogenic factors such as VEGF, and promote the formation of new blood vessels in skeletal muscle.…”

Section: Discussionmentioning

confidence: 99%

Application of recombinant peroxisome proliferator-activated receptor-γ coactivator-1α mediates neovascularization in the retina

Jiang

Zhang

et al. 2015

Molecular Medicine Reports

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Abstract. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is able to induce the expression of vascular endothelial growth factor (VEGF), promoting the formation of new blood vessels in skeletal muscle. The aim of the current study was to determine whether PGC-1α is able to regulate angiogenesis in human retinal vascular endothelial cells (hRVECs) in vitro and in retinas in vivo. hRVECs treated with recombinant PGC-1α were incubated for 24 h and then placed into a normoxic (20% O 2 ) or hypoxic (1% O 2 ) environment for a further 16 h. Following this, VEGF mRNA and protein levels were significantly increased. Cellular proliferation was enhanced by treatment with recombinant PGC-1α in normoxic and hypoxic conditions. At 24 h following recombinant PGC-1α treatment, hRVECs were plated into Matrigel-coated plates and cultured under normoxic (20% O 2 ) or hypoxic (1% O 2 ) conditions for a further 24 h. Recombinant PGC-1α-treated cells were observed to form significantly greater numbers of tubes. In a C57BL/6J mouse model of ischemic retinopathy, mice received an intravitreal injection of recombinant PGC-1α, resulting in a significant increase in VEGF mRNA and protein levels in the retina. Retinal neovascular tufts and neovascular nuclei were investigated by angiographic and cross-sectional analysis and were observed to be significantly increased in the PGC-1α group compared with the control group. These results indicate that PGC-1α is able to induce angiogenesis in hRVECs and retinas, and suggests that PGC-1α is a potential anti-angiogenic target in retinal neovascularization.

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The key role of PGC-1α in mitochondrial biogenesis and the proliferation of pulmonary artery vascular smooth muscle cells at an early stage of hypoxic exposure

Cited by 17 publications

References 29 publications

Resveratrol Protects Against Pulmonary Arterial Hypertension in Rats via Activation of Silent Information Regulator 1

Resveratrol Protects Against Pulmonary Arterial Hypertension in Rats via Activation of Silent Information Regulator 1

PGC-1α plays a major role in the anti-apoptotic effect of 15-HETE in pulmonary artery endothelial cells

Application of recombinant peroxisome proliferator-activated receptor-γ coactivator-1α mediates neovascularization in the retina

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