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      Electro-Acupuncture at Neiguan Pretreatment Alters Genome-Wide Gene Expressions and Protects Rat Myocardium against Ischemia-Reperfusion

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          Abstract

          This study investigated genome-wide gene expressions and the cardioprotective effects of electro-acupuncture pretreatment at the PC6 Neiguan acupoint on myocardial ischemia reperfusion (I/R) injury. Male SD rats were randomly divided into four groups: sham operation (SO), I/R, electro-acupuncture at the PC6 Neiguan acupoint pretreatment (EA) and electro-acupuncture at non-acupoint pretreatment (NA). Compared with the I/R group, the survival rate of the EA group was significantly increased, the arrhythmia score, infarction area, serum concentrations of CK, LDH and CK-Mb and plasma level of cTnT were significantly decreased. RNA-seq results showed that 725 genes were up-regulated and 861 genes were down-regulated under I/R conditions compared to the SO group; both EA and NA reversed some of these gene expression levels (592 in EA and 238 in NA group). KEGG pathway analysis indicated that these genes were involved in multiple pathways, including ECM, MAPK signaling, apoptosis, cytokine and leukocyte pathways. In addition, some pathways were uniquely regulated by EA, but not NA pretreatment, such as oxidative stress, cardiac muscle contraction, gap junction, vascular smooth muscle contraction, hypertrophic, NOD-like receptor, and P53 and B-cell receptor pathways. This study was first to reveal the gene expression signatures of acute myocardial I/R injury and electro-acupuncture pretreatment in rats.

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          VDAC1: from structure to cancer therapy

          Varda Shoshan-Barmatz, Dario Mizrachi (2012)
          Here, we review current evidence pointing to the function of VDAC1 in cell life and death, and highlight these functions in relation to cancer. Found at the outer mitochondrial membrane, VDAC1 assumes a crucial position in the cell, controlling the metabolic cross-talk between mitochondria and the rest of the cell. Moreover, its location at the boundary between the mitochondria and the cytosol enables VDAC1 to interact with proteins that mediate and regulate the integration of mitochondrial functions with other cellular activities. As a metabolite transporter, VDAC1 contributes to the metabolic phenotype of cancer cells. This is reflected by VDAC1 over-expression in many cancer types, and by inhibition of tumor development upon silencing VDAC1 expression. Along with regulating cellular energy production and metabolism, VDAC1 is also a key protein in mitochondria-mediated apoptosis, participating in the release of apoptotic proteins and interacting with anti-apoptotic proteins. The involvement of VDAC1 in the release of apoptotic proteins located in the inter-membranal space is discussed, as is VDAC1 oligomerization as an important step in apoptosis induction. VDAC also serves as an anchor point for mitochondria-interacting proteins, some of which are also highly expressed in many cancers, such as hexokinase (HK), Bcl2, and Bcl-xL. By binding to VDAC, HK provides both metabolic benefit and apoptosis-suppressive capacity that offers the cell a proliferative advantage and increases its resistance to chemotherapy. VDAC1-based peptides that bind specifically to HK, Bcl2, or Bcl-xL abolished the cell’s abilities to bypass the apoptotic pathway. Moreover, these peptides promote cell death in a panel of genetically characterized cell lines derived from different human cancers. These and other functions point to VDAC1 as a rational target for the development of a new generation of therapeutics.
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            Quantification of arrhythmias using scoring systems: an examination of seven scores in an in vivo model of regional myocardial ischaemia.

            M Kate Curtis, Bruce Walker (1988)
            Arrhythmia scores have been used in recent years to facilitate the analysis of arrhythmias, particularly in relation to regional myocardial ischaemia. The recent Lambeth Conventions recommended caution in the use of arrhythmia scores since their use may be misleading. In the present study seven scoring systems were examined in an attempt to validate the use of arrhythmia scores. A strong positive correlation was present between all seven scores. Furthermore, the scores all correlated with the incidences of ventricular fibrillation, ventricular tachycardia, and ventricular premature beats in early myocardial ischaemia. All seven scores successfully detected statistically significant reductions in the incidence of ventricular fibrillation resulting from the administration of two drugs. Some of the scores occasionally showed statistically significant reductions when effects on the raw arrhythmia data were not statistically significant. In this respect, parametric statistical analysis of arrhythmia scores may be a more sensitive method of quantifying arrhythmias than non-parametric analysis of binomially distributed raw data such as the incidence of ventricular fibrillation (in accordance with the power of such tests) indicating that the scores have precision. However, none of the scores incorrectly showed a statistically significant reduction when the raw data expressed a statistically significant or non-significant increase, indicating that the scores have accuracy. In conclusion, it is possible to design many arrhythmia scores that show changes in arrhythmia severity when more conventional analyses show only non-statistically significant trends. When used in conjunction with raw arrhythmia data, comprehensive drug dose ranges, and appropriate parametric statistical tests, arrhythmia scores facilitate the quantification of arrhythmias. It is recommended that arrhythmia scores should be used only for quantifying group data and model building and not for prognostic purposes in individuals.
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              Essential Role of Voltage-Dependent Anion Channel in Various Forms of Apoptosis in Mammalian Cells

              Shigeomi Shimizu, Yosuke Matsuoka, Yasuo Shinohara … (2001)
              Through direct interaction with the voltage-dependent anion channel (VDAC), proapoptotic members of the Bcl-2 family such as Bax and Bak induce apoptogenic cytochrome c release in isolated mitochondria, whereas BH3-only proteins such as Bid and Bik do not directly target the VDAC to induce cytochrome c release. To investigate the biological significance of the VDAC for apoptosis in mammalian cells, we produced two kinds of anti-VDAC antibodies that inhibited VDAC activity. In isolated mitochondria, these antibodies prevented Bax-induced cytochrome c release and loss of the mitochondrial membrane potential (Δψ), but not Bid-induced cytochrome c release. When microinjected into cells, these anti-VDAC antibodies, but not control antibodies, also prevented Bax-induced cytochrome c release and apoptosis, whereas the antibodies did not prevent Bid-induced apoptosis, indicating that the VDAC is essential for Bax-induced, but not Bid-induced, apoptogenic mitochondrial changes and apoptotic cell death. In addition, microinjection of these anti-VDAC antibodies significantly inhibited etoposide-, paclitaxel-, and staurosporine-induced apoptosis. Furthermore, we used these antibodies to show that Bax- and Bak-induced lysis of red blood cells was also mediated by the VDAC on plasma membrane. Taken together, our data provide evidence that the VDAC plays an essential role in apoptogenic cytochrome c release and apoptosis in mammalian cells.
              Article 0 comments Cited 58 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Molecules
                Journal ID (iso-abbrev): Molecules
                Journal ID (publisher-id): molecules
                Title: Molecules
                Publisher: MDPI
                ISSN (Electronic): 1420-3049
                Publication date (Electronic): 09 October 2014
                Publication date Collection: October 2014
                Volume: 19
                Issue: 10
                Pages: 16158-16178
                Affiliations
                [1 ]Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, No. 138, Xianlin Rd, Nanjing 210023, Jiangsu, China; E-Mails: hyan0915@ 123456sina.com (Y.H.); lushengfeng2013@ 123456gmail.com (S.-F.L.); shuping.fu@ 123456gmail.com (S.-P.F.); weixingshen@ 123456sina.cn (W.-X.S.); wliu@ 123456vet.upenn.edu (W.-X.L.); liqian20140603@ 123456163.com (Q.L.); hebei@ 123456263.net (N.W.); weixiaosoon@ 123456163.com (S.-Y.H.)
                [2 ]School of Information Technology, Nanjing University of Chinese Medicine, No. 138, Xianlin Rd, Nanjing 210023, Jiangsu, China; E-Mail: hucjhyl@ 123456126.com
                [3 ]School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, No.1166, Liutai Avenue, Wenjiang District, Chengdu 611137, Sichuan, China; E-Mail: acu973@ 123456126.com
                Author notes
                [†]

                These authors contributed equally to this work.

                [* ]Author to whom correspondence should be addressed; E-Mail: zhubm64@ 123456hotmail.com ; Tel./Fax: +86-25-8581-1235.
                Article
                Publisher ID: molecules-19-16158
                DOI: 10.3390/molecules191016158
                PMC ID: 6271995
                PubMed ID: 25302705
                SO-VID: 107bba84-d531-440f-9252-1e99a8039792
                Copyright © © 2014 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 21 June 2014
                Date revision received : 12 September 2014
                Date accepted : 15 September 2014
                Categories
                Subject: Article

                Keywords: electro-acupuncture pretreatment,myocardial ischemia-reperfusion,rna-seq,gene expression profiling,pathway
                Data availability:
                Keywords: electro-acupuncture pretreatment, myocardial ischemia-reperfusion, rna-seq, gene expression profiling, pathway

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