Pterostilbene, a natural small-molecular compound, promotes cytoprotective macroautophagy in vascular endothelial cells

Zhang, Lu; Cui, Liuqing; Zhou, Guang‐Zhou; Jing, Huaiqi; Guo, Yuqi; Sun, Wenkai

doi:10.1016/j.jnutbio.2012.06.008

Cited by 50 publications

(43 citation statements)

References 34 publications

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“…23 Moreover, several natural compounds with anti-inflammatory or antioxidant activity (eg, curcumin, vitamin D, resveratrol, or the analogue pterostilbene) [24][25][26][27][28] promote autophagy in ECs to protect against endothelial inflammation or oxidative stress. However, oxidative stress induced by ROS or oxLDL may also affect the endoplasmic reticulum (ER), 20,29 inducing deregulation of cytosolic calcium, a condition known to trigger ER stress and apoptosis.…”

Section: Autophagy In the Normal Vessel Wall Autophagy Is A Cytoprotementioning

confidence: 99%

Autophagy in Vascular Disease

Meyer

Grootaert

Michiels

et al. 2015

Circulation Research

239

179

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A utophagy is a complex intracellular process that delivers cytoplasmic constituents for degradation into lysosomes.1,2 Three main types of autophagy have been described: (1) microautophagy, comprising direct engulfment of cytoplasmic material by lysosomes via inward invaginations of the lysosomal membrane, (2) macroautophagy, characterized by formation of double-membrane sequestering compartments termed autophagosomes that fuse with lysosomes for delivery of cytoplasmic cargo, and (3) chaperone-mediated autophagy, mediated by a chaperone complex and lysosomal-associated membrane protein type 2A to degrade cytosolic proteins with a specific targeting motif. The term autophagy usually refers to macroautophagy, which is the most prevalent and beststudied form of autophagy. Also in this review, we will focus exclusively on macroautophagy, further cited as autophagy.Autophagy occurs at basal levels in most tissues to allow constitutive turnover of cytosolic components but is stimulated by environmental stress-related signals (eg, nutrient deprivation and oxidative injury) to recycle nutrients and to generate energy for maintenance of cell viability in unfavorable conditions.1 In addition to cellular stress, basal autophagy can be intensified by specific drugs, 3 indicating that the autophagic machinery is a potential therapeutic target for diverse diseases. Indeed, given that autophagy is involved in the prevention

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Section: Autophagy In the Normal Vessel Wall Autophagy Is A Cytoprotementioning

confidence: 99%

Autophagy in Vascular Disease

Meyer

Grootaert

Michiels

et al. 2015

Circulation Research

239

179

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“…Pterostilbene promoted autophagy via a rapid elevation of intracellular calcium concentration and subsequent activation of AMPKa1 [128]. Another form of autophagy induction was observed after cells' treatment with Marchantin M. This proteasome inhibitor decreased mTOR protein levels [85] or inhibited mTOR activators pospho-Akt and 3-phosphoinositide-dependent protein kinase-1 (PDK1) [87].…”

Section: Pi3k/akt/mtormentioning

confidence: 99%

Crosstalk between autophagy and proteasome protein degradation systems: possible implications for cancer therapy

Wójcik

2014

Folia Histochem Cytobiol.

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Abstract:The Ubiquitin-Proteasomes System (UPS) and autophagy, two main intracellular protein degradation pathways within the eukaryotic cells which were originally regarded as rather independent, seem to be very closely related. Proteasome inhibitors, including the multipathway inhibitor bortezomib, are drawing increased attention for their therapeutic potential in the treatment of chronic inflammation and cancer, especially tumours with a high degree of malignancy. The over-activation of autophagy induces cell death and may act as a powerful tumour-suppressing mechanism. However, autophagy, serving as an important mechanism to generate nutrients in time of cellular stresses, may directly contribute to the survival of cells treated with proteasome inhibitors, and in consequence, may decrease the effectiveness of therapy. Results of studies performed on several cancer cell lines demonstrated synergy between proteasome inhibitors and autophagy inhibitors. Those results became the base for ongoing clinical trials investigating autophagy inhibition in combination with anti-cancer therapies, including bortezomib. This review provides summary of the latest data on the functioning of the UPS and the mechanisms of autophagy. The new insights describing the main pathways of autophagy activation in response to UPS inhibition related to: (i) Unfolded Protein Response, (ii) PI3K/Akt/mTOR pathway, and (iii) formation of aggresomes, are discussed. It is concluded that concomitant inhibition of the two main cellular protein degradation systems may provide new therapeutic modalities for cancer treatment.

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“…Therefore, manipulation with AMPK has been suggested to be a potential therapeutic approach to cure cardiac ischemic diseases where enhanced cardiac resistance to stress is indispensable. In addition, PT can stimulate AMPK activity to induce suppressive effects on fat accumulation and apoptosis in both adipocytes and vascular endothelial cells [21, 22]. In our study, myocardial IR significantly increased p-AMPK levels in diabetic rats, and the rise of p-AMPK was not sufficient to combat apoptosis, and this led to the enhanced cardiac oxidative stress and apoptosis in diabetic hearts.…”

Section: Discussionmentioning

confidence: 63%

AMPK Contributes to Cardioprotective Effects of Pterostilbene Against Myocardial Ischemia- Reperfusion Injury in Diabetic Rats by Suppressing Cardiac Oxidative Stress and Apoptosis

Kosuru

Cai

Kandula³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Pterostilbene (PT) exerts antidiabetic effects by decreasing blood glucose and modulating lipid metabolism and has been shown to attenuate myocardial ischemia-reperfusion (IR) injury in non-diabetic subjects. However, whether PT can protect against myocardial IR injury in diabetes is unknown. AMPK stimulation is indispensable in offering cardioprotection against myocardial IR injury in diabetes by limiting cardiac apoptosis. Thus, we hypothesized that PT may confer protection against myocardial IR injury in diabetes via AMPK activation. Methods: Sprague-Dawley rats at eight weeks of diabetes induction (induced by an intravenous dose of 65 mg/kg streptozotocin) were administered with vehicle or PT (20 and 40 mg/kg/day, p.o.) for four weeks (starting from week 9 to 12). At the end of week 12, myocardial IR injury was induced by subjecting the diabetic rats to 30 minutes of coronary artery ligation and followed by 2 hours of reperfusion. In in vitro studies, rat primary cardiomyocytes were incubated with low glucose (LG, 5.5 mM) or high glucose (HG, 30 mM) and exposed to 45 minutes hypoxia and 2 hours reoxygenation in the presence or absence of PT (0.5 µM) or the AMPK inhibitor compound C (CC, 5 µM). Results: PT significantly reduced post-ischemic cardiac infarct size, oxidative stress, plasma lactate dehydrogenase (LDH), creatine kinase-MB levels and apoptosis in diabetic rats. In cardiomyocytes, PT decreased hypoxia/ reoxygenation-induced oxidative stress, attenuated LDH and cleaved caspase3/caspase3 ratio and increased Bcl-2/Bax ratio and AMPK phosphorylation. However, CC administration blunted the cardioprotective effects of PT both in vivo and in vitro. Conclusion: Suppressing cardiac oxidative stress and apoptosis via AMPK stimulation may represent a primary mechanism whereby pterostilbene attenuates diabetic myocardial IR injury.

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Pterostilbene, a natural small-molecular compound, promotes cytoprotective macroautophagy in vascular endothelial cells

Cited by 50 publications

References 34 publications

Autophagy in Vascular Disease

Autophagy in Vascular Disease

Crosstalk between autophagy and proteasome protein degradation systems: possible implications for cancer therapy

AMPK Contributes to Cardioprotective Effects of Pterostilbene Against Myocardial Ischemia- Reperfusion Injury in Diabetic Rats by Suppressing Cardiac Oxidative Stress and Apoptosis

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