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Enzyme pkc delta

Binh Thanh Nguyen, Min Park, Jae-Chul Pyun, Young Sook Yoo, Min-Jung Kang
An assay for protein kinase C delta (PKCδ) activity based on the quantification of a synthetic substrate using capillary electrophoresis with laser-induced fluorescence detection was developed. The peptides labeled with fluorescein isothiocyanate F-ERK (where ERK is extracellular signal-regulated kinase) and the phosphorylated form, P-F-ERK, were utilized for the method development and validation. The migration time of F-ERK and P-F-ERK were 6.3 ± 0.1 and 8.7 ± 0.2 min, respectively. LOD and LOQ values of F-ERK were 2 and 6 ng/mL and those of P-F-ERK were 4 and 12 ng/mL...
December 2016: Electrophoresis
Nir Qvit, Amit U Joshi, Anna D Cunningham, Julio C B Ferreira, Daria Mochly-Rosen
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an important glycolytic enzyme, has a non-catalytic (thus a non-canonical) role in inducing mitochondrial elimination under oxidative stress. We recently demonstrated that phosphorylation of GAPDH by δ protein kinase C (δPKC) inhibits this GAPDH-dependent mitochondrial elimination. δPKC phosphorylation of GAPDH correlates with increased cell injury following oxidative stress, suggesting that inhibiting GAPDH phosphorylation should decrease cell injury. Using rational design, we identified pseudo-GAPDH (ψGAPDH) peptide, an inhibitor of δPKC-mediated GAPDH phosphorylation that does not inhibit the phosphorylation of other δPKC substrates...
June 24, 2016: Journal of Biological Chemistry
Jin Kawata, Rui Yamaguchi, Takatoshi Yamamoto, Yasuji Ishimaru, Arisa Sakamoto, Manabu Aoki, Masafumi Kitano, Misako Umehashi, Eiji Hirose, Yasuo Yamaguchi
OBJECTIVE: Neutrophils have an important role in the rapid innate immune response, and the release or active secretion of elastase from neutrophils is linked to various inflammatory responses. Purpose of this study was to determine how the human neutrophil elastase affects the interleukin-10 (IL-10) response in peripheral blood mononuclear cells (PBMC). MATERIALS AND METHODS: In this prospective study, changes in IL-10 messenger RNA (mRNA) and protein expression levels in monocytes derived from human PBMCs were investigated after stimulation with human neutrophil elastase (HNE)...
2016: Cell Journal
Patcharapong Thangsunan, Suriya Tateing, Supa Hannongbua, Nuttee Suree
Protein kinase C (PKC) isozymes are important regulatory enzymes that have been implicated in many diseases, including cancer, Alzheimer's disease, and in the eradication of HIV/AIDS. Given their potential clinical ramifications, PKC modulators, e.g. phorbol esters and bryostatin, are also of great interest in the drug development. However, structural details on the binding between PKC and its modulators, especially bryostatin - the highly potent and non-tumor promoting activator for PKCs, are still lacking...
July 2016: Journal of Biomolecular Structure & Dynamics
Mary K Sheats, Eui Jae Sung, Kenneth B Adler, Samuel L Jones
Dysregulated release of neutrophil reactive oxygen species and proteolytic enzymes contributes to both acute and chronic inflammatory diseases. Therefore, molecular regulators of these processes are potential targets for new anti-inflammatory therapies. We have shown previously that myristoylated alanine-rich C-kinase substrate (MARCKS), a well-known actin binding protein and protein kinase C (PKC) substrate, is a key regulator of neutrophil functions. In the current study, we investigate the role of PKC-mediated MARCKS phosphorylation in neutrophil migration and adhesion in vitro...
2015: Inflammation
Ruhul Amin, Sapna Sharma, Sireesha Ratakonda, Hatim A Hassan
Nephrolithiasis remains a major health problem in Western countries. Seventy to 80% of kidney stones are composed of calcium oxalate, and small changes in urinary oxalate affect risk of kidney stone formation. Intestinal oxalate secretion mediated by the anion exchanger SLC26A6 plays an essential role in preventing hyperoxaluria and calcium oxalate nephrolithiasis, indicating that understanding the mechanisms regulating intestinal oxalate transport is critical for management of hyperoxaluria. Purinergic signaling modulates several intestinal processes through pathways including PKC activation, which we previously found to inhibit Slc26a6 activity in mouse duodenal tissue...
July 1, 2013: American Journal of Physiology. Cell Physiology
Wing-Keung Chu, Pei-Min Dai, Hsin-Lun Li, Chia-Chu Pao, Jan-Kan Chen
Nanog is a transcription factor that is essential for the maintenance of pluripotency of the embryonic stem cells. Nanog has been shown to be expressed in various kinds of human tumors, suggesting a role in tumorigenesis. In this study, we found that Nanog expression was upregulated by inhibition of protein kinase C (PKC) activity in six human cancer cell lines examined. In a Nanog non-expressing human nasopharyngeal carcinoma cell line, NPC-076, Nanog mRNA level and protein level were both induced and dose-dependently promoted by exposure to PKC inhibitors...
July 2013: Carcinogenesis
Bradley R Webster, Jessica M Osmond, Daniel A Paredes, Xavier A DeLeon, Olan Jackson-Weaver, Benjimen R Walker, Nancy L Kanagy
Obstructive sleep apnea (OSA) is associated with cardiovascular complications including hypertension. Previous findings from our laboratory indicate that exposure to intermittent hypoxia (IH), to mimic sleep apnea, increases blood pressure in rats. IH also increases endothelin-1 (ET-1) constrictor sensitivity in a protein kinase C (PKC) δ-dependent manner in mesenteric arteries. Because phosphoinositide-dependent kinase-1 (PDK-1) regulates PKCδ activity, we hypothesized that PDK-1 contributes to the augmented ET-1 constrictor sensitivity and elevated blood pressure following IH...
January 2013: Journal of Pharmacology and Experimental Therapeutics
Derek Blair, Fay J Dufort, Thomas C Chiles
Signals derived from the BCR (B-cell antigen receptor) control survival, development and antigenic responses. One mechanism by which BCR signals may mediate these responses is by regulating cell metabolism. Indeed, the bioenergetic demands of naïve B-cells increase following BCR engagement and are characterized by a metabolic switch to aerobic glycolysis; however, the signalling pathways involved in this metabolic reprogramming are poorly defined. The PKC (protein kinase C) family plays an integral role in B-cell survival and antigenic responses...
November 15, 2012: Biochemical Journal
Ehsan Oskoueian, Norhani Abdullah, Syahida Ahmad
Jatropha meal produced from the kernel of Jatropha curcas Linn. grown in Malaysia contains phorbol esters (PEs). The potential benefits of PEs present in the meal as anticancer agent are still not well understood. Hence, this study was conducted to evaluate the cytotoxic effects and mode of actions of PEs isolated from Jatropha meal against breast (MCF-7) and cervical (HeLa) cancer cell lines. Isolated PEs inhibited cells proliferation in a dose-dependent manner of both MCF-7 and HeLa cell lines with the IC₅₀ of 128...
2012: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Meng Zhao, Li Xia, Guo-Qiang Chen
Protein kinase C-delta (PKCδ), a member of the lipid-regulated serine/threonine PKC family, has been implicated in a wide range of important cellular processes. In the past decade, the critical role of PKCδ in the regulation of both intrinsic and extrinsic apoptosis pathways has been widely explored. In most cases, over-expression or activation of PKCδ results in the induction of apoptosis. The phosphorylations and multiple cell organelle translocations of PKCδ initiate apoptosis by targeting multiple downstream effectors...
October 2012: Archivum Immunologiae et Therapiae Experimentalis
Seung Eun Lee, Hana Yang, Seong Il Jeong, Young-Ho Jin, Cheung-Seog Park, Yong Seek Park
BACKGROUND: Crotonaldehyde, an alpha, beta-unsaturated aldehyde present in cigarette smoke, is an environmental pollutant and a product of lipid peroxidation. It also produces adverse effects to humans and is considered as a risk factor for various diseases. Heme oxygenase-1 (HO-1) plays important roles in protecting cells against oxidative stress as a prime cellular defense mechanism. However, HO-1 may be associated with cell proliferation and resistance to apoptosis in cancer cells...
2012: PloS One
Pin Lv, Sui-Bing Miao, Ya-Nan Shu, Li-Hua Dong, George Liu, Xiao-Li Xie, Min Gao, Yu-Can Wang, Ya-Juan Yin, Xiao-Juan Wang, Mei Han
RATIONALE: We have demonstrated that smooth muscle (SM) 22α inhibits cell proliferation via blocking Ras-ERK1/2 signaling in vascular smooth muscle cells (VSMCs) and in injured arteries. The recent study indicates that SM22α disruption can independently promote arterial inflammation through activation of reactive oxygen species (ROS)-mediated NF-κB pathways. However, the mechanisms by which SM22α controls ROS production have not been characterized. OBJECTIVE: To investigate how SM22α disruption promotes ROS production and to characterize the underlying mechanisms...
August 31, 2012: Circulation Research
Robert V Stahelin, Kok-Fai Kong, Sumita Raha, Wen Tian, Heather R Melowic, Katherine E Ward, Diana Murray, Amnon Altman, Wonhwa Cho
Protein kinase Cθ (PKCθ) is a novel PKC that plays a key role in T lymphocyte activation. To understand how PKCθ is regulated in T cells, we investigated the properties of its N-terminal C2 domain that functions as an autoinhibitory domain. Our measurements show that a Tyr(P)-containing peptide derived from CDCP1 binds the C2 domain of PKCθ with high affinity and activates the enzyme activity of the intact protein. The Tyr(P) peptide also binds the C2 domain of PKCδ tightly, but no enzyme activation was observed with PKCδ...
August 31, 2012: Journal of Biological Chemistry
P Yi, L Schrott, T P Castor, J S Alexander
Activation of the α-secretase processing pathway of amyloid precursor protein (APP) is recognized as an important mechanism which diverts APP processing from production of beta-amyloid (Aβ) to non toxic sAPPα, decreasing Alzheimer's disease (AD) plaque formation and AD-associated cognitive deficits. Two potent classes of PKC modulators can activate the α-secretase pathway, the benzo/indolactams and bryostatin/bryologues. While both modulate PKC-dependent APP processing, no direct comparisons of their relative pharmacological potencies have been accomplished which could assist in the development of AD therapies...
September 2012: Journal of Molecular Neuroscience: MN
Yu-Jun Shen, Shan-Shan Pan, Jun Ge, Zhe Hao
The objective of this study was to investigate the early cardioprotective effect of exercise preconditioning (EP) on the exhaustive exercise-induced myocardial injury in rats and the role of protein kinase C delta isoform (PKCδ) in EP. Rats were subjected to run on the treadmill for four periods of 10 min each at 30 m/min with intervening periods of rest of 10 min as an EP protocol. The exhaustive exercise was performed 0.5 h after EP. PKC inhibitor chelerythrine (CHE) was injected before EP. Our results showed that EP markedly attenuated the exhaustive exercise-induced myocardial ischemia/hypoxia, ultrastructural damage, high serum cTnI, and NT-proBNP levels...
September 2012: Molecular and Cellular Biochemistry
Xiaoqing Gan, Jiyong Wang, Chen Wang, Eeva Sommer, Tohru Kozasa, Srinivasa Srinivasula, Dario Alessi, Stefan Offermanns, Melvin I Simon, Dianqing Wu
Mammalian target of rapamycin complex 2 (mTORC2) phosphorylates AGC protein kinases including protein kinase C (PKC) and regulates cellular functions such as cell migration. However, its regulation remains poorly understood. Here we show that lysophosphatidic acid (LPA) induces two phases of PKC-δ hydrophobic motif phosphorylation. The late phase is mediated by Gα(12), which specifically activates ARAF, leading to upregulation of the RFFL E3 ubiquitin ligase and subsequent ubiquitylation and degradation of the PRR5L subunit of mTORC2...
May 20, 2012: Nature Cell Biology
Tihomir Miralem, Nicole Lerner-Marmarosh, Peter E M Gibbs, Cicerone Tudor, Fred K Hagen, Mahin D Maines
PKCδ, a Ser/Thr kinase, promotes cell growth, tumorigenesis, and apoptosis. Human biliverdin reductase (hBVR), a Ser/Thr/Tyr kinase, inhibits apoptosis by reducing biliverdin-IX to antioxidant bilirubin. The enzymes are activated by similar stimuli. Reportedly, hBVR is a kinase-independent activator of PKCδ and is transactivated by the PKC (Gibbs, P. E., Miralem, T., Lerner-Marmarosh, N., Tudor, C., and Maines, M. D. (2012) J. Biol. Chem. 287, 1066-1079). Presently, we examined interactions between the two proteins in the context of regulation of their activities and defining targets of hBVR phosphorylation by PKCδ...
July 13, 2012: Journal of Biological Chemistry
Kazuhiro Irie, Ryo C Yanagita, Yu Nakagawa
Protein kinase C (PKC) isozymes are widely recognized as targets for anticancer therapy, and recent investigations demonstrated that PKC activators are potential therapeutic candidates for Alzheimer's disease and acquired immune deficiency syndrome. However, concerns exist about their therapeutic uses because most PKC activators are potent tumor promoters. Bryostatin 1 (bryo-1) is a unique PKC activator with little tumor-promoting activities. Bryo-1 is currently undergoing clinical trials for the treatment of cancer...
May 2012: Medicinal Research Reviews
Y C Muñoz, G I Gomez, M Moreno, C L Solis, L E Valladares, V Velarde
The steroid hormone dehydroepiandrosterone (DHEA), suggested to be a cardioprotector, prevents platelet aggregation in healthy humans. This hormone is reduced in postmenopausal women by 60% of its normal value. Platelets in patients with type 2 diabetes (T2D) are more sensitive to aggregation, which has been attributed to a reduced ability to produce nitric oxide (NO). In light of these precedents and considering that DHEA is able to increase the production of NO in cultured endothelial cells, we suggest that DHEA prevents the aggregation of platelet from postmenopausal women with T2D through the activation of PKC/eNOS/NO/cGMP pathway...
July 2012: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
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