Propofol-induced activation of protein kinase C isoforms in adult rat ventricular myocytes.

Published on May 1, 2006in Anesthesiology6.424
· DOI :10.1097/00000542-200605000-00013
Peter J. Wickley7
Estimated H-index: 7
Xueqin Ding7
Estimated H-index: 7
+ 1 AuthorsDerek S. Damron23
Estimated H-index: 23
Background: Myocardial protection by anesthetics is known to involve activation of protein kinase C (PKC). The authors’ objective was to identify the PKC isoforms activated by propofol in rat ventricular myocytes. They also assessed the intracellular location of individual PKC isoforms before and after treatment with propofol. Methods: Freshly isolated ventricular myocytes were obtained from adult rat hearts. Immunoblot analysis of cardiomyocyte subcellular fractions was used to assess translocation of individual PKC isoforms before and after exposure to propofol. An enzyme-linked immunosorbent assay kit was used for measuring PKC activity. Immunocytochemistry and confocal microscopy were used to visualize the intracellular location of the individual PKC isoforms. Results: Under baseline conditions, PKC-α, PKC-δ, and PKC-ζ were associated with both the cytosolic and membrane fractions, whereas PKC-e was exclusively located in the cytosolic fraction. Propofol (10 μm) caused translocation of PKC-α, PKC-δ, PKC-e, and PKC-ζ from cytosolic to membrane fraction and increased total PKC activity (211 ± 17% of baseline; P = 0.003) in a dose-dependent manner. Immunocytochemical localization of the individual PKC isoforms demonstrated that propofol caused translocation of PKC-α to the intercalated discs and z-lines; PKC-δ to the perinuclear region; PKC-e to sites associated with the z-lines, intercalated discs, and the sarcolemma; and PKC-ζ to the nucleus. Conclusions: These results demonstrate that propofol causes an increase in PKC activity in rat ventricular myocytes. Propofol stimulates translocation of PKC-α, PKC-δ, PKC-e, and PKC-ζ to distinct intracellular sites in cardiomyocytes. This may be a fundamentally important cellular mechanism of anesthesia-induced myocardial protection in the setting of ischemia–reperfusion injury.
  • References (42)
  • Citations (39)
📖 Papers frequently viewed together
93 Citations
141 Citations
147 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Noriaki KanayaH-Index: 7
#2Brad GableH-Index: 3
Last. Derek S. DamronH-Index: 23
view all 5 authors...
Background: The rationale for this study is that the depressant effect of propofol on cardiac function in vitro is highly variable but may be explained by differences in the temperature and stimulation frequency used for the study. Both temperature and stimulation frequency are known to modulate cellular mechanisms that regulate intracellular free Ca 2+ concentration ([Ca 2+ ] i ) and myofilament Ca 2+ sensitivity in cardiac muscle. The authors hypothesized that temperature and stimulation frequ...
12 CitationsSource
#1Brad GableH-Index: 3
#2Toshiya ShigaH-Index: 12
Last. Derek S. DamronH-Index: 23
view all 4 authors...
Background: The objective of this study was to identify the extent to which propofol alters intracellular free Ca 2+ concentration ([Ca 2+ ] i ), myofilament Ca 2+ sensitivity, and contraction of individual cardiomyocytes during activation of α 1a adrenoreceptors and to determine the cellular mechanism of action. Methods: Freshly isolated ventricular myocytes were obtained from adult rat hearts. Myocyte shortening and [Ca 2+ ] i were simultaneously monitored in individual cardiomyocytes exposed ...
11 CitationsSource
#1Misuk Kang (UW: University of Wisconsin-Madison)H-Index: 5
#2Jeffery W. Walker (UW: University of Wisconsin-Madison)H-Index: 34
To examine cardiac contractile regulation and protein kinase C (PKC) translocation in parallel, the d and e isoforms of PKC were fused to green fluorescent protein (GFP) and expressed in adult rat ventricular myocytes maintained in short term culture. PKC-d-GFP and PKC-eGFP were predominantly cytosolic until phorbol dibutyrate (PDBu) was introduced. PKC-d-GFP redistributed preferentially to perinuclear structures that co-localized with a Golgi marker, whereas PKC-e-GFP redistributed preferential...
40 CitationsSource
#1Detlef ObalH-Index: 15
#2Nina C. WeberH-Index: 25
Last. W. SchlackH-Index: 16
view all 10 authors...
BACKGROUND: Volatile anaesthetics precondition the heart against infarction, an effect partly mediated by activation of the epsilon isoform of protein kinase C (PKCepsilon). We investigated whether cardioprotection by activation of PKCepsilon depends on the isoflurane concentration. METHODS: Anaesthetized rats underwent 25 min of coronary artery occlusion followed by 120 min of reperfusion and were randomly assigned to the following groups (n=10 in each group): isoflurane preconditioning induced...
41 CitationsSource
#1Detlef ObalH-Index: 15
#2Nina C. WeberH-Index: 25
Last. W. SchlackH-Index: 16
view all 9 authors...
The invention provides a structure of a front part of a vehicle body that is simple and free from the risk of maloperation. In the event of a collision between the vehicle and a pedestrian, a projecting part sweeps the pedestrian by parts of his or her legs lower than the knees in the event of a collision between the vehicle and the pedestrian, causing the pedestrian to be thrown over toward the vehicle, and after an energy-absorbing member has absorbed impact energy exerted on the legs, the ped...
12 Citations
#1Pengcheng XuH-Index: 1
#2Jun WangH-Index: 14
Last. Ira S. KassH-Index: 22
view all 5 authors...
Isoflurane enhances myocardial functional recovery and improves energy levels after ischemia. We sought to determine whether isoflurane-induced cardioprotection is mediated by protein kinase C (PKC). The Langendorff model was used, and isolated perfused rat hearts were separated into untreated, isoflurane, chelerythrine (PKC inhibitor) plus isoflurane, and chelerythrine groups. All hearts were subjected to treatment before ischemia, followed by 30 min of ischemia and 60 min of reperfusion. We re...
14 CitationsSource
#1Katsuya TanakaH-Index: 18
#2Lynda M. LudwigH-Index: 10
Last. David C. WarltierH-Index: 72
view all 5 authors...
238 CitationsSource
#1Michael Zaugg (UZH: University of Zurich)H-Index: 31
#2Eliana Lucchinetti (UZH: University of Zurich)H-Index: 28
Last. Marcus C. Schaub (UZH: University of Zurich)H-Index: 40
view all 5 authors...
Cardiac preconditioning represents the most potent and consistently reproducible method of rescuing heart tissue from undergoing irreversible ischaemic damage. Major milestones regarding the elucidation of this phenomenon have been passed in the last two decades. The signalling and amplification cascades from the preconditioning stimulus, be it ischaemic or pharmacological, to the putative end-effectors, including the mechanisms involved in cellular protection, are discussed in this review. Vola...
224 CitationsSource
#1Leo G. KevinH-Index: 14
#2Peter KatzH-Index: 1
Last. David F. StoweH-Index: 44
view all 6 authors...
Background Anesthetic preconditioning (APC) is protective for several aspects of cardiac function and structure, including left ventricular pressure, coronary flow, and infarction. APC may be protective, however, only if the duration of ischemia is within a certain, as yet undefined range. Brief ischemia causes minimal injury, and APC would be expected to provide little benefit. Conversely, very prolonged ischemia would ultimately cause serious injury with or without APC. Previous investigations...
38 CitationsSource
#1Enis NovalijaH-Index: 20
#2Leo G. KevinH-Index: 14
Last. David F. StoweH-Index: 44
view all 6 authors...
Background Protein kinase C (PKC) and reactive oxygen species (ROS) are known to have a role in anesthetic preconditioning (APC). Cardiac preconditioning by triggers other than volatile anesthetics, such as opioids or brief ischemia, is known to be isoform selective, but the isoform required for APC is not known. The authors aimed to identify the PKC isoform that is involved in APC and to elucidate the relative positions of PKC activation and ROS formation in the APC signaling cascade. Methods I...
102 CitationsSource
Cited By39
#1Spencer R. Andrei (VUMC: Vanderbilt University Medical Center)H-Index: 3
#2Monica Ghosh (KSU: Kent State University)H-Index: 2
Last. Derek S. Damron (KSU: Kent State University)H-Index: 11
view all 4 authors...
ABSTRACTThe functional expression of transient receptor potential cation channel of the ankyrin-1 subtype (TRPA1) has recently been identified in adult mouse cardiac tissue where stimulation of this ion channel leads to increases in adult mouse ventricular cardiomyocyte (CM) contractile function via a Ca2+-Calmodulin-dependent kinase (CaMKII) pathway. However, the extent to which TRPA1 induces nitric oxide (NO) production in CMs, and whether this signaling cascade mediates physiological or patho...
#1Takeshi Miyahara (Hiroshima University)
#2Naoko Adachi (Kobe University)H-Index: 11
Last. Norio Sakai (Hiroshima University)H-Index: 32
view all 8 authors...
Abstract Propofol is the most commonly used anesthetic. Immunohistochemical studies have reported that propofol translocated protein kinase Cs (PKCs) in cardiomyocyte in a subtype-specific manner; however detailed features of the propofol-induced translocation of PKCs remain unknown. In this study, we performed real-time observation of propofol-induced PKC translocation in SH-SY5Y cells expressing PKCs fused with a fluorescent protein. Propofol unidirectionally translocated γPKC-GFP, a conventio...
#1Gao Haiying (Ha Tai: Xiamen University)H-Index: 1
#2Han Mingjie (Ha Tai: Xiamen University)H-Index: 1
Last. Zhang Bing-xi (Beijing Tongren Hospital)H-Index: 1
view all 6 authors...
Abstract Background Extracellular signal-regulated kinase 1/2 (ERK1/2) has been implicated in learning and memory; however, whether intravenous anesthetics modulate ERK1/2 remains unknown. The aim of this study was to examine the effect of several intravenous anesthetics on the phosphorylation of ERK1/2 in the hippocampus of adult mice. Methods Western blotting was used to examine cellular levels of phosphorylated and unphosphorylated ERK1/2 in mouse hippocampus slices, which were incubated with...
6 CitationsSource
#1Yang‑Chao Wei (GLMU: Guilin Medical University)H-Index: 1
#2Bin ZhangH-Index: 2
Last. Yang Li (GLMU: Guilin Medical University)H-Index: 6
view all 10 authors...
Abstract δ‑opioid receptor (DOR) belongs to the family of G protein‑coupled receptors (GPCRs). Numerous studies have shown that DOR is widely distributed in human peripheral tissues and is closely related to the development and progression of certain malignant tumours. However, there is controversy in the literature regarding whether DOR has an impact on the development and progression of human breast cancer. The present study comprehensively elaborates on the biological functions of DOR by dete...
5 CitationsSource
#1Spencer R. Andrei (KSU: Kent State University)H-Index: 3
#2Pritam Sinharoy (KSU: Kent State University)H-Index: 6
Last. Derek S. Damron (KSU: Kent State University)H-Index: 11
view all 4 authors...
ABSTRACTTransient receptor potential channels of the ankyrin subtype-1 (TRPA1) and vanilloid subtype-1 (TRPV1) are structurally related, non-selective cation channels that show a high permeability to calcium. Previous studies indicate that TRP channels play a prominent role in the regulation of cardiovascular dynamics and homeostasis, but also contribute to the pathophysiology of many diseases and disorders within the cardiovascular system. However, no studies to date have identified the functio...
14 CitationsSource
#1Jayant Shravah (UBC: University of British Columbia)H-Index: 3
#2Baohua Wang (UBC: University of British Columbia)H-Index: 6
Last. David M. Ansley (UBC: University of British Columbia)H-Index: 20
view all 7 authors...
We previously demonstrated that propofol, an intravenous anesthetic with anti-oxidative properties, activated the phosphoinositide 3-kinase (PI3K)/AKT pathway to increase the expression of B cell lymphoma (Bcl)-2 and, therefore the anti-apoptotic potential on cardiomyocytes. Here, we wanted to determine if propofol can also activate the Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 pathway, another branch of cardioprotective signaling. The cellular response of nu...
17 CitationsSource
#1Long Wang ('SMMU': Second Military Medical University)H-Index: 1
#2Wei-Feng Yu ('SMMU': Second Military Medical University)H-Index: 1
Abstract The causes of obstructive jaundice are varied, but it is most commonly due to choledocholithiasis; benign strictures of the biliary tract; pancreaticobiliary malignancies; and metastatic disease. Surgery in patients with obstructive jaundice is generally considered to be associated with a higher incidence of complications and mortality. Therefore, it poses a considerable challenge to the anesthesiologist, surgeons, and the intensive care team. However, appropriate preoperative evaluatio...
7 CitationsSource
#1Chuantao SuoH-Index: 1
#2Libo Sun (JLU: Jilin University)H-Index: 1
Last. Shuang Yang (HMU: Harbin Medical University)H-Index: 1
view all 3 authors...
Alpinetin is a natural flavonoid that protects cells against fatal injury in ischemia-reperfusion. δ receptor activation protects myocardial cells from trauma; however, the mechanism is unknown. The aim of this study was to explore the function of alpinetin in δ receptor-mediated myocardial apoptosis. The myocardial cells of newly born rats were cultivated and myocardial apoptosis was induced by serum deprivation. The MTT method was used to evaluate cell viability and Annexin V-fluorescein isoth...
8 CitationsSource
#1Shaoqing LeiH-Index: 17
#2Wating SuH-Index: 6
Last. Zhengyuan XiaH-Index: 32
view all 10 authors...
Continuous treatment with organic nitrates causes nitrate tolerance and endothelial dysfunction, which is involved with protein kinase C (PKC) signal pathway and NADPH oxidase activation. We determined whether chronic administration with nitroglycerine compromises the protective effects of propofol against tumor necrosis factor (TNF-) induced toxicity in endothelial cells by PKC-β2 dependent NADPH oxidase activation. Primary cultured human umbilical vein endothelial cells were either treated or ...
8 CitationsSource
#1Janet R. Manning (University of Cincinnati Academic Health Center)H-Index: 3
#2Sarah O. Perkins (Ontario Veterinary College)H-Index: 1
Last. Jo El J. Schultz (University of Cincinnati Academic Health Center)H-Index: 26
view all 8 authors...
Among its many biological roles, fibroblast growth factor-2 (FGF2) acutely protects the heart from dysfunction associated with ischemia/reperfusion (I/R) injury. Our laboratory has demonstrated that this is due to the activity of the low molecular weight (LMW) isoform of FGF2 and that FGF2-mediated cardioprotection relies on the activity of protein kinase C (PKC); however, which PKC isoforms are responsible for LMW FGF2-mediated cardioprotection, and their downstream targets, remain to be elucid...
3 CitationsSource