Senescence marker protein 30: functional and structural insights to its unknown physiological function

Scott, Stephanie H.; Bahnson, Brian J.

doi:10.1515/bmc.2011.041

Cited by 27 publications

(30 citation statements)

References 75 publications

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“…26,31,32) The lungs of the SMP30-deficient mice in the current study did not show a significant increase of medial smooth muscle area in either normoxia or hypoxia. Although SMP30 has an anti-apoptosis effect, [33][34][35] further study is needed to clarify the survival of pulmonary arterial smooth muscle cells in hypoxia-exposed SMP30-deficient mice. There was no difference in the Fulton index between WT and SMP30 deficient mice after hypoxia in this study.…”

Section: Discussionmentioning

confidence: 99%

Senescence Marker Protein 30 Deficiency Exacerbates Pulmonary Hypertension in Hypoxia-Exposed Mice

et al. 2019

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Pulmonary arterial hypertension is a fatal disease caused by pulmonary arterial vasoconstriction and organic stenosis due to the proliferation of pulmonary smooth muscle cells and endothelial cells. Endothelial dysfunction, including impaired nitric oxide (NO) bioavailability, plays a crucial role in the pathogenesis of pulmonary hypertension, and endothelial nitric oxide synthase (eNOS) is an important modulator of pulmonary vasodilatation. Although senescence marker protein (SMP) 30 is known as an anti-aging protein, the role of SMP30 in pulmonary vessels is still unclear. In this study, we examined the role of SMP30 in pulmonary vasculature using SMP30-deficient mice. We used female SMP30-deficient mice and wild-type littermate (WT) mice at the age of 12 to 18 weeks. The WT and SMP30-deficient mice were exposed to normoxia or hypoxia (10% oxygen for 4 weeks). In normoxia, the right ventricular systolic pressure (RVSP) was not different between the WT and SMP30-deficient mice, but in hypoxia, the RVSP was significantly higher in the SMP30-deficient mice compared to the WT mice (P < 0.05). The hypoxia-induced increases in right ventricular hypertrophy and medial smooth muscle area of the pulmonary artery were comparable between the WT and the SMP30-deficient mice. Western blotting showed that eNOS phosphorylation in lung tissue was reduced in the SMP30-deficient mice compared to the WT mice in normoxia. However, in hypoxic conditions, eNOS phosphorylation was reduced in both the WT and SMP30-deficient mice with no differences in Akt phosphorylation. Our study demonstrated that SMP30 is involved in the development of hypoxia-induced pulmonary hypertension by impairment of eNOS activity.

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Section: Discussionmentioning

confidence: 99%

Senescence Marker Protein 30 Deficiency Exacerbates Pulmonary Hypertension in Hypoxia-Exposed Mice

et al. 2019

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“…Suppression of p21 levels by Id1 augments the generation of EPCs in bone marrow . SMP30, a marker of senescence or aging, protects cells from apoptosis by inhibiting the caspase cascade and regulating Ca 2+ homeostasis . SMP30 has also been found to exert a protective effect against oxidative stress by enhancing ascorbate production and Ca 2+ modulation .…”

Section: Discussionmentioning

confidence: 99%

The Sulfated Polysaccharide Fucoidan Rescues Senescence of Endothelial Colony-Forming Cells for Ischemic Repair

Lee

Choi

et al. 2015

Stem Cells

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The efficacy of cell therapy using endothelial colony-forming cells (ECFCs) in the treatment of ischemia is limited by the replicative senescence of isolated ECFCs in vitro. Such senescence must therefore be overcome in order for such cell therapies to be clinically applicable. This study aimed to investigate the potential of sulfated polysaccharide fucoidan to rescue ECFCs from cellular senescence and to improve in vivo vascular repair by ECFCs. Fucoidanpreconditioning of senescent ECFCs was shown by flow cytometry to restore the expression of functional ECFC surface markers (CD34, c-Kit, VEGFR2, and CXCR4) and stimulate the in vitro tube formation capacity of ECFCs. Fucoidan also promoted the expression of cell cycleassociated proteins (cyclin E, Cdk2, cyclin D1, and Cdk4) in senescent ECFCs, significantly reversed cellular senescence, and increased the proliferation of ECFCs via the FAK, Akt, and ERK signaling pathways. Fucoidan was found to enhance the survival, proliferation, incorporation, and endothelial differentiation of senescent ECFCs transplanted in ischemic tissues in a murine hind limb ischemia model. Moreover, ECFC-induced functional recovery and limb salvage were markedly improved by fucoidan pretreatment of ECFCs. To our knowledge, the findings of our study are the first to demonstrate that fucoidan enhances the neovasculogenic potential of ECFCs by rescuing them from replicative cellular senescence. Pretreatment of ECFCs with fucoidan may thus provide a novel strategy for the application of senescent stem cells to therapeutic neovascularization.

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“…In addition, Matsumoto et al showed that cytosolic calcium regulates autophagy-related gene expression in autophagy-deficient mice [18] and that cytosolic Ca 2+ signaling is a critical regulator of cardiac myocyte function [13]. A pivotal anti-senescence marker, SMP30 (senescence marker protein 30), has been reported to regulate intracellular Ca 2+ homeostasis [19,20,21] and play a pathophysiological role in the tight regulation of Ca 2+ -related cell functions [22]. Recently, intracellular Ca 2+ signaling has been reported to have an important role in the regulation of autophagy [23]; however, its exact function remains controversial.…”

Section: Introductionmentioning

confidence: 99%

Doxorubicin Regulates Autophagy Signals via Accumulation of Cytosolic Ca2+ in Human Cardiac Progenitor Cells

Park

Choi

Kim

et al. 2016

IJMS

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Doxorubicin (DOXO) is widely used to treat solid tumors. However, its clinical use is limited by side effects including serious cardiotoxicity due to cardiomyocyte damage. Resident cardiac progenitor cells (hCPCs) act as key regulators of homeostasis in myocardial cells. However, little is known about the function of hCPCs in DOXO-induced cardiotoxicity. In this study, we found that DOXO-mediated hCPC toxicity is closely related to calcium-related autophagy signaling and was significantly attenuated by blocking mTOR signaling in human hCPCs. DOXO induced hCPC apoptosis with reduction of SMP30 (regucalcin) and autophagosome marker LC3, as well as remarkable induction of the autophagy-related markers, Beclin-1, APG7, and P62/SQSTM1 and induction of calcium-related molecules, CaM (Calmodulin) and CaMKII (Calmodulin kinase II). The results of an LC3 puncta assay further indicated that DOXO reduced autophagosome formation via accumulation of cytosolic Ca2+. Additionally, DOXO significantly induced mTOR expression in hCPCs, and inhibition of mTOR signaling by rapamycin, a specific inhibitor, rescued DOXO-mediated autophagosome depletion in hCPCs with significant reduction of DOXO-mediated cytosolic Ca2+ accumulation in hCPCs, and restored SMP30 and mTOR expression. Thus, DOXO-mediated hCPC toxicity is linked to Ca2+-related autophagy signaling, and inhibition of mTOR signaling may provide a cardio-protective effect against DOXO-mediated hCPC toxicity.

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Senescence marker protein 30: functional and structural insights to its unknown physiological function

Cited by 27 publications

References 75 publications

Senescence Marker Protein 30 Deficiency Exacerbates Pulmonary Hypertension in Hypoxia-Exposed Mice

Senescence Marker Protein 30 Deficiency Exacerbates Pulmonary Hypertension in Hypoxia-Exposed Mice

The Sulfated Polysaccharide Fucoidan Rescues Senescence of Endothelial Colony-Forming Cells for Ischemic Repair

Doxorubicin Regulates Autophagy Signals via Accumulation of Cytosolic Ca2+ in Human Cardiac Progenitor Cells

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