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Article: Virotherapy, gene transfer and immunostimulatory monoclonal antibodies.

Nemchenko, Andriy

2012 Volume 1, Issue 8, Page(s) 1226

Language	English
Publishing date	2012-11-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2645309-5
ISSN	2162-402X ; 2162-4011
ISSN (online)	2162-402X
ISSN	2162-4011
DOI	10.4161/onci.22839
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Article ; Online: There is more to autophagy than induction: regulating the roller coaster.

Klionsky, Daniel J / Nemchenko, Andriy

Autophagy

2011 Volume 7, Issue 8, Page(s) 801–802

Abstract: Considerable attention has been paid to the topic of autophagy induction. In part, this is because of the potential for modulating this process for therapeutic purposes. Of course we know that induced autophagy can also be problematic--for example, when ... ...

Abstract	Considerable attention has been paid to the topic of autophagy induction. In part, this is because of the potential for modulating this process for therapeutic purposes. Of course we know that induced autophagy can also be problematic--for example, when trying to eliminate an established tumor that might be relying on autophagy for its own cytoprotective uses. Accordingly, inhibitory mechanisms have been considered; however, the corresponding studies have tended to focus on the pathways that block autophagy under non-inducing conditions, such as when nutrients are available. In contrast, relatively little is known about the mechanisms for inhibiting autophagy under inducing conditions. Yet, this type of regulation must be occurring on a routine basis. We know that dysregulation of autophagy, e.g., due to improper activation of Beclin 1 leading to excessive autophagy activity, can cause cell death. Accordingly, we assume that during starvation or other inducing conditions there must be a mechanism to modulate autophagy. That is, once you turn it on, you do not want to let it continue unchecked. But how is autophagy downregulated when the inducing conditions still exist?
MeSH term(s)	Animals ; Autophagy ; Down-Regulation ; Humans ; TOR Serine-Threonine Kinases/metabolism
Chemical Substances	TOR Serine-Threonine Kinases (EC 2.7.1.1)
Language	English
Publishing date	2011-08-01
Publishing country	United States
Document type	Introductory Journal Article
ZDB-ID	2454135-7
ISSN	1554-8635 ; 1554-8627
ISSN (online)	1554-8635
ISSN	1554-8627
DOI	10.4161/auto.7.8.16609
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Article ; Online: NEMO nuances NF-kappaB.

Nemchenko, Andriy / Hill, Joseph A

Circulation research

2010 Volume 106, Issue 1, Page(s) 10–12

MeSH term(s)	Animals ; Antioxidants/metabolism ; Cardiomyopathy, Dilated/genetics ; Cardiomyopathy, Dilated/metabolism ; Cells, Cultured ; Gene Deletion ; Heart Failure/genetics ; Heart Failure/metabolism ; Humans ; I-kappa B Kinase/genetics ; I-kappa B Kinase/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Male ; Mice ; Myocytes, Cardiac/metabolism ; NF-kappa B/genetics ; NF-kappa B/metabolism ; Oxidative Stress ; Signal Transduction
Chemical Substances	Antioxidants ; Intracellular Signaling Peptides and Proteins ; NEMO protein, mouse ; NF-kappa B ; I-kappa B Kinase (EC 2.7.11.10)
Language	English
Publishing date	2010-01-07
Publishing country	United States
Document type	Comment ; Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.109.211185
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Article: Duplicate maize 13-lipoxygenase genes are differentially regulated by circadian rhythm, cold stress, wounding, pathogen infection, and hormonal treatments.

Nemchenko, Andriy / Kunze, Susan / Feussner, Ivo / Kolomiets, Michael

Journal of experimental botany

2006 Volume 57, Issue 14, Page(s) 3767–3779

Abstract: Most plant oxylipins, a large class of diverse oxygenated polyunsaturated fatty acids and their derivatives, are produced through the lipoxygenase (LOX) pathway. Recent progress in dicots has highlighted the biological roles of oxylipins in plant defence ...

Abstract	Most plant oxylipins, a large class of diverse oxygenated polyunsaturated fatty acids and their derivatives, are produced through the lipoxygenase (LOX) pathway. Recent progress in dicots has highlighted the biological roles of oxylipins in plant defence responses to pathogens and pests. By contrast, the physiological function of LOXs and their metabolites in monocots is poorly understood. Two maize LOXs, ZmLOX10 and ZmLOX11 that share >90% amino acid sequence identity but are localized on different chromosomes, were cloned and characterized. Phylogenetic analysis revealed that ZmLOX10 and ZmLOX11 cluster together with well-characterized plastidic type 2 linoleate 13-LOXs from diverse plant species. Regio-specificity analysis of recombinant ZmLOX10 protein overexpressed in Escherichia coli proved it to be a linoleate 13-LOX with a pH optimum at approximately pH 8.0. Both predicted proteins contain putative transit peptides for chloroplast import. ZmLOX10 was preferentially expressed in leaves and was induced in response to wounding, cold stress, defence-related hormones jasmonic acid (JA), salicylic acid (SA), and abscisic acid (ABA), and inoculation with an avirulent strain of Cochliobolus carbonum. These data suggested a role for this gene in maize adaptation to abiotic stresses and defence responses against pathogens and pests. ZmLOX11 was preferentially expressed in silks and was induced in leaves only by ABA, indicating its possible involvement in responses to osmotic stress. In leaves, mRNA accumulation of ZmLOX10 is strictly regulated by a circadian rhythm, with maximal expression coinciding temporally with the highest photosynthetic activity. This study reveals the evolutionary divergence of physiological roles for relatively recently duplicated genes. Possible physiological functions of these 13-LOXs are suggested.
MeSH term(s)	Abscisic Acid/pharmacology ; Ascomycota/physiology ; Circadian Rhythm ; Cloning, Molecular ; Cold Temperature ; Escherichia coli/genetics ; Gene Expression Regulation, Plant ; Genes, Duplicate ; Hydrogen-Ion Concentration ; Lipoxygenase/chemistry ; Lipoxygenase/genetics ; Lipoxygenase/metabolism ; Photosynthesis ; Phylogeny ; Plant Growth Regulators/pharmacology ; Plant Proteins/chemistry ; Plant Proteins/genetics ; Plant Proteins/metabolism ; Promoter Regions, Genetic ; Recombinant Fusion Proteins/analysis ; Sequence Analysis, Protein ; Zea mays/genetics ; Zea mays/metabolism ; Zea mays/microbiology
Chemical Substances	Plant Growth Regulators ; Plant Proteins ; Recombinant Fusion Proteins ; Abscisic Acid (72S9A8J5GW) ; 13-lipoxygenase (EC 1.13.11.-) ; Lipoxygenase (EC 1.13.11.12)
Language	English
Publishing date	2006
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2976-2
ISSN	1460-2431 ; 0022-0957
ISSN (online)	1460-2431
ISSN	0022-0957
DOI	10.1093/jxb/erl137
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Article ; Online: Autophagy as a therapeutic target in cardiovascular disease.

Nemchenko, Andriy / Chiong, Mario / Turer, Aslan / Lavandero, Sergio / Hill, Joseph A

Journal of molecular and cellular cardiology

2011 Volume 51, Issue 4, Page(s) 584–593

Abstract: The epidemic of heart failure continues apace, and development of novel therapies with clinical efficacy has lagged. Now, important insights into the molecular circuitry of cardiovascular autophagy have raised the prospect that this cellular pathway of ... ...

Abstract	The epidemic of heart failure continues apace, and development of novel therapies with clinical efficacy has lagged. Now, important insights into the molecular circuitry of cardiovascular autophagy have raised the prospect that this cellular pathway of protein quality control may be a target of clinical relevance. Whereas basal levels of autophagy are required for cell survival, excessive levels - or perhaps distinct forms of autophagic flux - contribute to disease pathogenesis. Our challenge will be to distinguish mechanisms that drive adaptive versus maladaptive autophagy and to manipulate those pathways for therapeutic gain. Recent evidence suggests this may be possible. Here, we review the fundamental biology of autophagy and its role in a variety of forms of cardiovascular disease. We discuss ways in which this evolutionarily conserved catabolic mechanism can be manipulated, discuss studies presently underway in heart disease, and provide our perspective on where this exciting field may lead in the future. This article is part of a special issue entitled ''Key Signaling Molecules in Hypertrophy and Heart Failure.''
MeSH term(s)	Adenylate Kinase/antagonists & inhibitors ; Adenylate Kinase/metabolism ; Animals ; Autophagy/drug effects ; Cardiomegaly/drug therapy ; Cardiomegaly/metabolism ; Cardiomegaly/physiopathology ; Cardiovascular Agents/therapeutic use ; Chromatin Assembly and Disassembly ; Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Heart Failure/drug therapy ; Heart Failure/metabolism ; Heart Failure/physiopathology ; Histone Acetyltransferases/metabolism ; Histone Deacetylase Inhibitors/therapeutic use ; Histone Deacetylases/metabolism ; Humans ; Inositol 1,4,5-Trisphosphate Receptors/antagonists & inhibitors ; Inositol 1,4,5-Trisphosphate Receptors/metabolism ; Mechanistic Target of Rapamycin Complex 1 ; Molecular Targeted Therapy ; Multiprotein Complexes ; Myocardium/metabolism ; Myocardium/pathology ; Proteins/antagonists & inhibitors ; Proteins/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases ; Tumor Suppressor Protein p53/agonists ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Cardiovascular Agents ; Histone Deacetylase Inhibitors ; Inositol 1,4,5-Trisphosphate Receptors ; Multiprotein Complexes ; Proteins ; TP53 protein, human ; Tumor Suppressor Protein p53 ; Histone Acetyltransferases (EC 2.3.1.48) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11) ; Adenylate Kinase (EC 2.7.4.3) ; Histone Deacetylases (EC 3.5.1.98)
Language	English
Publishing date	2011-06-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80157-4
ISSN	1095-8584 ; 0022-2828
ISSN (online)	1095-8584
ISSN	0022-2828
DOI	10.1016/j.yjmcc.2011.06.010
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Article: Duplicate maize 13-lipoxygenase genes are differentially regulated by circadian rhythm, cold stress, wounding, pathogen infection, and hormonal treatments

Nemchenko, Andriy / Kunze, Susan / Feussner, Ivo / Kolomiets, Michael

Journal of experimental botany. 2006 Nov., v. 57, no. 14

2006

Abstract	Most plant oxylipins, a large class of diverse oxygenated polyunsaturated fatty acids and their derivatives, are produced through the lipoxygenase (LOX) pathway. Recent progress in dicots has highlighted the biological roles of oxylipins in plant defence responses to pathogens and pests. By contrast, the physiological function of LOXs and their metabolites in monocots is poorly understood. Two maize LOXs, ZmLOX10 and ZmLOX11 that share >90% amino acid sequence identity but are localized on different chromosomes, were cloned and characterized. Phylogenetic analysis revealed that ZmLOX10 and ZmLOX11 cluster together with well-characterized plastidic type 2 linoleate 13-LOXs from diverse plant species. Regio-specificity analysis of recombinant ZmLOX10 protein overexpressed in Escherichia coli proved it to be a linoleate 13-LOX with a pH optimum at ~pH 8.0. Both predicted proteins contain putative transit peptides for chloroplast import. ZmLOX10 was preferentially expressed in leaves and was induced in response to wounding, cold stress, defence-related hormones jasmonic acid (JA), salicylic acid (SA), and abscisic acid (ABA), and inoculation with an avirulent strain of Cochliobolus carbonum. These data suggested a role for this gene in maize adaptation to abiotic stresses and defence responses against pathogens and pests. ZmLOX11 was preferentially expressed in silks and was induced in leaves only by ABA, indicating its possible involvement in responses to osmotic stress. In leaves, mRNA accumulation of ZmLOX10 is strictly regulated by a circadian rhythm, with maximal expression coinciding temporally with the highest photosynthetic activity. This study reveals the evolutionary divergence of physiological roles for relatively recently duplicated genes. Possible physiological functions of these 13-LOXs are suggested.
Keywords	Zea mays ; corn ; lipoxygenase ; genes ; gene expression ; gene expression regulation ; circadian rhythm ; cold stress ; plant damage ; plant pathogens ; salicylic acid ; polyunsaturated fatty acids ; amino acid sequences ; nucleotide sequences ; chromosome mapping ; phylogeny ; enzyme activity ; pH ; leaves ; jasmonic acid ; abscisic acid
Language	English
Dates of publication	2006-11
Size	p. 3767-3779.
Document type	Article
ZDB-ID	2976-2
ISSN	1460-2431 ; 0022-0957
ISSN (online)	1460-2431
ISSN	0022-0957
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Diabetic cardiomyopathy and metabolic remodeling of the heart.

Battiprolu, Pavan K / Lopez-Crisosto, Camila / Wang, Zhao V / Nemchenko, Andriy / Lavandero, Sergio / Hill, Joseph A

Life sciences

2012 Volume 92, Issue 11, Page(s) 609–615

Abstract: The incidence and prevalence of diabetes mellitus are both increasing rapidly in societies around the globe. The majority of patients with diabetes succumb ultimately to heart disease, much of which stems from atherosclerotic disease and hypertension. ... ...

Abstract	The incidence and prevalence of diabetes mellitus are both increasing rapidly in societies around the globe. The majority of patients with diabetes succumb ultimately to heart disease, much of which stems from atherosclerotic disease and hypertension. However, the diabetic milieu is itself intrinsically noxious to the heart, and cardiomyopathy can develop independent of elevated blood pressure or coronary artery disease. This process, termed diabetic cardiomyopathy, is characterized by significant changes in the physiology, structure, and mechanical function of the heart. Presently, therapy for patients with diabetes focuses largely on glucose control, and attention to the heart commences with the onset of symptoms. When the latter develops, standard therapy for heart failure is applied. However, recent studies highlight that specific elements of the pathogenesis of diabetic heart disease are unique, raising the prospect of diabetes-specific therapeutic intervention. Here, we review recently unveiled insights into the pathogenesis of diabetic cardiomyopathy and associated metabolic remodeling with an eye toward identifying novel targets with therapeutic potential.
MeSH term(s)	Diabetic Cardiomyopathies/drug therapy ; Diabetic Cardiomyopathies/pathology ; Drug Delivery Systems ; Humans ; Ventricular Remodeling
Language	English
Publishing date	2012-10-30
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2012.10.011
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Article: Diabetic cardiomyopathy and metabolic remodeling of the heart

Battiprolu, Pavan K / Lopez-Crisosto, Camila / Wang, Zhao V / Nemchenko, Andriy / Lavandero, Sergio / Hill, Joseph A

Life sciences. 2013 Mar. 28, v. 92, no. 11

2013

Abstract	The incidence and prevalence of diabetes mellitus are both increasing rapidly in societies around the globe. The majority of patients with diabetes succumb ultimately to heart disease, much of which stems from atherosclerotic disease and hypertension. However, the diabetic milieu is itself intrinsically noxious to the heart, and cardiomyopathy can develop independent of elevated blood pressure or coronary artery disease. This process, termed diabetic cardiomyopathy, is characterized by significant changes in the physiology, structure, and mechanical function of the heart. Presently, therapy for patients with diabetes focuses largely on glucose control, and attention to the heart commences with the onset of symptoms. When the latter develops, standard therapy for heart failure is applied. However, recent studies highlight that specific elements of the pathogenesis of diabetic heart disease are unique, raising the prospect of diabetes-specific therapeutic intervention. Here, we review recently unveiled insights into the pathogenesis of diabetic cardiomyopathy and associated metabolic remodeling with an eye toward identifying novel targets with therapeutic potential.
Keywords	blood pressure ; cardiomyopathy ; coronary artery disease ; diabetes mellitus ; glycemic control ; heart ; heart failure ; hypertension ; pathogenesis ; patients ; therapeutics
Language	English
Dates of publication	2013-0328
Size	p. 609-615.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2012.10.011
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Article: The novel monocot-specific 9-lipoxygenase ZmLOX12 is required to mount an effective jasmonate-mediated defense against Fusarium verticillioides in maize.

Christensen, Shawn A / Nemchenko, Andriy / Park, Yong-Soon / Borrego, Eli / Huang, Pei-Cheng / Schmelz, Eric A / Kunze, Susan / Feussner, Ivo / Yalpani, Nasser / Meeley, Robert / Kolomiets, Michael V

Molecular plant-microbe interactions : MPMI

2014 Volume 27, Issue 11, Page(s) 1263–1276

Abstract: Fusarium verticillioides is a major limiting factor for maize production due to ear and stalk rot and the contamination of seed with the carcinogenic mycotoxin fumonisin. While lipoxygenase (LOX)-derived oxylipins have been implicated in defense against ... ...

Abstract	Fusarium verticillioides is a major limiting factor for maize production due to ear and stalk rot and the contamination of seed with the carcinogenic mycotoxin fumonisin. While lipoxygenase (LOX)-derived oxylipins have been implicated in defense against diverse pathogens, their function in maize resistance against F. verticillioides is poorly understood. Here, we functionally characterized a novel maize 9-LOX gene, ZmLOX12. This gene is distantly related to known dicot LOX genes, with closest homologs found exclusively in other monocot species. ZmLOX12 is predominantly expressed in mesocotyls in which it is strongly induced in response to F. verticillioides infection. The Mutator transposon-insertional lox12-1 mutant is more susceptible to F. verticillioides colonization of mesocotyls, stalks, and kernels. The infected mutant kernels accumulate a significantly greater amount of the mycotoxin fumonisin. Reduced resistance to the pathogen is accompanied by diminished levels of the jasmonic acid (JA) precursor 12-oxo phytodienoic acid, JA-isoleucine, and expression of jasmonate-biosynthetic genes. Supporting the strong defense role of jasmonates, the JA-deficient opr7 opr8 double mutant displayed complete lack of immunity to F. verticillioides. Unexpectedly, the more susceptible lox12 mutant accumulated higher levels of kauralexins, suggesting that F. verticillioides is tolerant to this group of antimicrobial phytoalexins. This study demonstrates that this unique monocot-specific 9-LOX plays a key role in defense against F. verticillioides in diverse maize tissues and provides genetic evidence that JA is the major defense hormone against this pathogen.
MeSH term(s)	Amino Acid Sequence ; Cyclopentanes/metabolism ; Fumonisins/metabolism ; Fusarium/pathogenicity ; Fusarium/physiology ; Lipoxygenase/genetics ; Lipoxygenase/metabolism ; Molecular Sequence Data ; Mutagenesis, Insertional ; Organ Specificity ; Oxylipins/metabolism ; Plant Diseases/immunology ; Plant Diseases/microbiology ; Plant Growth Regulators/metabolism ; Plant Immunity ; Plant Proteins/genetics ; Plant Proteins/metabolism ; Plants, Genetically Modified ; Seedlings/enzymology ; Seedlings/genetics ; Seedlings/immunology ; Seedlings/microbiology ; Seeds/enzymology ; Seeds/genetics ; Seeds/immunology ; Seeds/microbiology ; Sequence Alignment ; Sequence Analysis, DNA ; Zea mays/enzymology ; Zea mays/genetics ; Zea mays/immunology ; Zea mays/microbiology
Chemical Substances	Cyclopentanes ; Fumonisins ; Oxylipins ; Plant Growth Regulators ; Plant Proteins ; jasmonic acid (6RI5N05OWW) ; Lipoxygenase (EC 1.13.11.12)
Language	English
Publishing date	2014-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	743331-1
ISSN	1943-7706 ; 0894-0282
ISSN (online)	1943-7706
ISSN	0894-0282
DOI	10.1094/MPMI-06-13-0184-R
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Article: The Novel Monocot-Specific 9-Lipoxygenase ZmLOX12 Is Required to Mount an Effective Jasmonate-Mediated Defense Against Fusarium verticillioides in Maize

Christensen, Shawn A / Borrego Eli / Feussner Ivo / Huang Pei-Cheng / Kolomiets Michael V / Kunze Susan / Meeley Robert / Nemchenko Andriy / Park Yong-Soon / Schmelz Eric A / Yalpani Nasser

Molecular plant-microbe interactions. 2014 Nov., v. 27, no. 11

2014

Abstract	Fusarium verticillioides is a major limiting factor for maize production due to ear and stalk rot and the contamination of seed with the carcinogenic mycotoxin fumonisin. While lipoxygenase (LOX)-derived oxylipins have been implicated in defense against diverse pathogens, their function in maize resistance against F. verticillioides is poorly understood. Here, we functionally characterized a novel maize 9-LOX gene, ZmLOX12. This gene is distantly related to known dicot LOX genes, with closest homologs found exclusively in other monocot species. ZmLOX12 is predominantly expressed in mesocotyls in which it is strongly induced in response to F. verticillioides infection. The Mutator transposon-insertional lox12-1 mutant is more susceptible to F. verticillioides colonization of mesocotyls, stalks, and kernels. The infected mutant kernels accumulate a significantly greater amount of the mycotoxin fumonisin. Reduced resistance to the pathogen is accompanied by diminished levels of the jasmonic acid (JA) precursor 12-oxo phytodienoic acid, JA-isoleucine, and expression of jasmonate-biosynthetic genes. Supporting the strong defense role of jasmonates, the JA-deficient opr7 opr8 double mutant displayed complete lack of immunity to F. verticillioides. Unexpectedly, the more susceptible lox12 mutant accumulated higher levels of kauralexins, suggesting that F. verticillioides is tolerant to this group of antimicrobial phytoalexins. This study demonstrates that this unique monocot-specific 9-LOX plays a key role in defense against F. verticillioides in diverse maize tissues and provides genetic evidence that JA is the major defense hormone against this pathogen.
Keywords	corn ; crop production ; fumonisins ; Fusarium verticillioides ; genes ; immunity ; jasmonic acid ; Liliopsida ; lipoxygenase ; Magnoliopsida ; mesocotyls ; mutants ; oxylipins ; pathogens ; phytoalexins ; seeds ; tissues
Language	English
Dates of publication	2014-11
Size	p. 1263-1276.
Publishing place	The American Phytopathological Society
Document type	Article
ZDB-ID	743331-1
ISSN	1943-7706 ; 0894-0282
ISSN (online)	1943-7706
ISSN	0894-0282
DOI	10.1094%2FMPMI-06-13-0184-R
Database	NAL-Catalogue (AGRICOLA)

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