About OMICS International Conferences

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1 About OMICS Group OMICS Group is an amalgamation of Open Access publications and worldwide international science conferences and events. Established in the year 2007 with the sole aim of making the information on Sciences and technology Open Access, OMICS Group publishes 500 online open access scholarly journals in all aspects of Science, Engineering, Management and Technology journals. OMICS Group has been instrumental in taking the knowledge on Science & technology to the doorsteps of ordinary men and women. Research Scholars, Students, Libraries, Educational Institutions, Research centers and the industry are main stakeholders that benefitted greatly from this knowledge dissemination. OMICS Group also organizes 500 International conferences annually across the globe, where knowledge transfer takes place through debates, round table discussions, poster presentations, workshops, symposia and exhibitions.

2 About OMICS International Conferences OMICS International is a pioneer and leading science event organizer, which publishes around 500 open access journals and conducts over 500 Medical, Clinical, Engineering, Life Sciences, Pharma scientific conferences all over the globe annually with the support of more than 1000 scientific associations and 30,000 editorial board members and 3.5 million followers to its credit. OMICS Group has organized 500 conferences, workshops and national symposiums across the major cities including San Francisco, Las Vegas, San Antonio, Omaha, Orlando, Raleigh, Santa Clara, Chicago, Philadelphia, Baltimore, United Kingdom, Valencia, Dubai, Beijing, Hyderabad, Bengaluru and Mumbai.

3 The phospholipid enzyme Pcyt2 is a new target for oxidative stress and heart disease Marica Bakovic Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada August 2015

4 Kennedy Pathway DAG/TAG Pathway Ethanolamine G3P EK ATP FA GPAT P-Eth Pcyt2 CTP CDP-Eth DAG FA PAP LPA PA AGPAT EPT DGAT PE FA TAG Pcyt2 regulates DAG partitioning between PE and TAG

5 A. Pcyt2 Splicing Pcyt2β 74 ATG 1-6 Exon-skipping TGA 1486 Pcyt2α Pcyt2γ 85 ATG 57 ATG B. Pcyt2 Proteins GT TT 1-6 7a 8a Intron-retention N-Domain Linker C-Domain 1297 TGA 960 TGA Pcyt2 α Pcyt2 β HYGH 244 HIGH of Exon HYGH HIGH Pcyt2γ HYGH

6 N αd S282 S205 (223α) S197 (215α) αf αl αa αa αd αl αc αb S191 αe αe αb S145,T146 T147 C J Biol Chem 2014

7 Control 50 um Meclizine Meclizine Story 6h at 37C 80% Methanol extraction Separation and Identification of Metabolites by LC-MS Meclizine (RS)-1-[(4-chlorophenyl)(phenyl) methyl]-4-(3-methylbenzyl)piperazine J Biol Chem 2013

8 Meclizine is a non-competitive inhibitor of Pcyt2 with respect to CTP A B B 14 C-Etn (pmol) 14 C-PE (pm mol) Etn PEtn CDP-Etn Ctrl Mec Ctrl Mec Ctrl_6h Mec_6h Ctrl 24h Mec 24h C 250 D 1/[V] No inhibitor 30 µm Mec µm Mec µm Mec /[S]

9 linker Proteomics Pcyt2 α N-CAT spliced out in β C-CAT J Biol Chem 2014 Pcyt2 β N-CAT 192, 209, 195, 215, PKC 300, 308 C-CAT B. Pcyt2α shared [ P S 223 GKEP 227 ] 145, 157, 146, 162, , , A. Pcyt2α specific [ P S 192 EV P S 195 SQCPG 200 ] P S 223 P S 192 P S 195 (-Serum) (-Serum)

10 F. Pcyt2α phosphorylation with PKCα 207 GVSQFLQT p S 215 QKI 18 P S 215 (b1 11) (b1-8) = p S G. Pcyt2α phosphorylation with PKCα T p S 215 Q P S 215 (b1-4)-(b1-3)= p S A. PMA 0 30 min 1h 2h C. PMA PMA+GO6976 PMA+EGF-R p Ser p Ser Pcyt2 total Pcyt2 total B. Pyct2 enzyme activity (pmol/mg/min) min 1h 2h D. Pcyt2 enzyme activity (pmol/mg/min) PMA PMA+GO6976 PMA+EGF-R J Biol Chem 2014

11 A. Anti- P Ser Anti-V5 C. Pcyt2α S A PMA EGF-R Anti- P Ser Anti-V5 B. D. Endogenous Overexpressed Pcyt2 activity (pmol/mg/min) PMA (nm) J Biol Chem 2014

12 A Pcyt2 α N-Domain Linker C-Domain PKRRGIF of Exon Pcyt2 γ 291 RGD 293 B Pcyt2 α N Pcyt2 γ N C C Gene 2014

13 Pcyt2γ is a dominant negative isoform Pcyt2γ Pcyt2α Pcyt2β Ctrl Pcyt2γ 37kDa β-tubulin IP: Pcyt2γ IP: Pcyt2α Pcyt2α 50kDa Pcyt2γ 37 kda Pcyt2γ 37kDa Pcyt2α 50kDa Dimerization Pcyt2α Dimer (100kDa) Gene 2014

14 Mutants of active isoforms are also inhibitors Activity Pcyt2α Pcyt2α+H244Y Pcyt2α+H35Y 50kDa α-myc β-tubilin Dimerization Pcyt2α Pcyt2α Pcyt2α H244Y H35 Y Pcyt2α Pcyt2α +H244Y Pcyt2α + H35Y Pcyt2α+H244Y Pcyt2α+H244Y Pcyt2α+H35Y Pcyt2α+H35Y 224 bp Pcyt2α mrna 100kDa Gene 2014

15 Pcyt2α homodimers are active α α γ Heterodimers and aggregates are inactive α c γ γ? γ α γ α α γ γ γ Gene 2014

16 Pcyt2 deficient mouse ETKO 50 Male +/- Male +/+ We eight (g) P<0.05 Female +/- Female +/+ WT Pcyt2 +/ Time (wks) J Biol. Chem 2009

17 A. Pcyt2 +/+ Pcyt2 +/- B. Pcyt2 +/+ Pcyt2 +/- m rer LD m LD 1µm 1µm Liver fibrosis Electron microscopy of liver reatic islets Liver lipid droplets m m m 200µm 200µm C. Pcyt2 +/+ Pcyt2 +/- D. Pcyt2 +/+ Pcyt2 +/- Pancr E. 200µm 200µm 100µm 100µm Pcyt2 +/+ Pcyt2 +/- Mol Cell Biol 2015 Male hearts

18 p<0.05 p<0.05 mrna (fold change) mrna (fold change) Microarray analysis Mol Cell Biol 2015

19 Gender effect on ETKO heart genes A. Male Pcyt2+/+ Pcyt2+/- Female Pcyt2+/+ Pcyt2+/- B. p<0.05 Mct1 Ace1 Pgc1α Scd1 Arbitrary unit Arbitrary unit Pcyt2 +/+ Pcyt2 +/- Pcyt2 +/+ Pcyt2 +/- Gapdh Male Female C. D. E. p<0.01 Arbitrary unit p<0.05 Arbitrary unit p<0.001 Male Female Male Female Male Female Mol Cell Biol 2015

20 A PC/PE Ratio % Total PE Arbitrary units % Total PI Pcyt2: +/+ +/- +/+ +/- Male Female Pcyt2: +/+ +/- +/+ +/- Male Female Pcyt2: +/+ +/- +/+ +/- Male Female B. F atty acids (% Phospholipids) 16:0 18:0 18:1 18:2 22:6 Pcyt2 +/+ Pcyt2 +/- Pcyt2 +/+ Pcyt2 +/- Female Male C. Fatty acids (% TAG) 16:0 16:1 18:0 18:1 18:2 Pcyt2 +/- Female Pcyt2 +/+ Male Pcyt2 +/- Male Pcyt2 +/+ Female Heart Lipid Dimorphism Mol Cell Biol 2015

21 N-6 PUFA synthesis and oxidative stress % 18:2 n-6 A. Linoleic acid % 20:3 n-6 Dihomo γ linolenic acid B. % 22:3 n-6 Docosatrienoic acid Docosahesaneoic acid % 22:6 n-3 % 20:4 n-6 % 22:4 n-6 % 22:5 n-6 Male Female Male Female TAG mg/g Arachidonic acid Docosatetranoic acid Male Female Docosapentaneoic acid Male Female C. TBARS (µm) Heart Male Female TBARS (µm) Aorta Male Female Pcyt2+/+ Pcyt2+/- Mol Cell Biol 2015

22 Male Pcyt2 +/- Heart Female 20:3 20:4 22:3 22:4 23:4 PC/PE Fatty acids Cd36 Glut4 TAG Ace1 Mct1 Glucose PI3K pakt pampk Fatty acids Glucose Cd36 Glut4 PC/PE TAG PI3K pakt pampk Scd1 Mct1 Enriched in n-6 fatty acids Unmodified n-6 fatty acids Impaired heart function Hypertension, Hypertrophy Normal heart function Male-specific heart disease Mol Cell Biol 2015

23 Pulami Albert Maida Leanne Ratnesh Laila Zvezdan Sugash

24 Let Us Meet Again We welcome you all to our future conferences of OMICS International Please Visit: molecular-biology-conferences.php