scholarly journals Mitochondrial Antisense RNA for Cytochrome C Oxidase (MARCO) Can Induce Morphologic Changes and Cell Death in Human Hematopoietic Cell Lines

Blood ◽  
1997 ◽  
Vol 90 (11) ◽  
pp. 4567-4577 ◽  
Author(s):  
Naoki Shirafuji ◽  
Satoshi Takahashi ◽  
Satoru Matsuda ◽  
Shigetaka Asano
Keyword(s):  
Molecular Weight ◽  
Cell Death ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Antisense Rna ◽  
Mitochondrial Gene ◽  
Neutrophilic Granulocytes ◽  
High Molecular Weight Dna ◽  
Tnf Α ◽  
Morphologic Changes

Abstract To identify essential molecules capable of inducing terminal morphologic maturation and cell death of myeloid progenitor cells, we isolated cDNA clones by functional expression cloning using a library constructed from all-trans retinoic acid (ATRA)-treated human promyelocytic HL-60 cells. Clones which induced morphologic changes in HL-60 cells from blastic cells to mature neutrophilic granulocytes were selected. The isolated positive cDNA clone was demonstrated to encode an antisense RNA for cytochrome c oxidase/serine tRNA derived from a mitochondrial gene (MARCO). When MARCO was expressed in HL-60 cells with the lac switch system, blastic cell morphology became neutrophilic after 48-hour incubation with IPTG, and cell death was observed after 3 days. Also, high molecular weight DNA fragmentation was observed after 36 hours in culture. Similar results were observed using transformants from human K562 cells and CMK cells. RT-PCR analysis revealed that MARCO was transcribed in both ATRA and TNF-α systems, and also in human blood neutrophilic granulocytes. Following transfection with cytochrome c oxidase expression plasmids, TNF-α–induced high molecular weight DNA fragmentation in U937 cells and HL-60 cells was inhibited in these transformants. These results indicate that maturational changes in hematopoietic cells and the process of cell death may be induced by mitochondrial respiratory insufficiency, and also that the mitochondrial gene MARCO may be used as one of the candidates for gene supplementation therapy for the acute leukemias.

scholarly journals Mitochondrial Antisense RNA for Cytochrome C Oxidase (MARCO) Can Induce Morphologic Changes and Cell Death in Human Hematopoietic Cell Lines

Blood ◽  
1997 ◽  
Vol 90 (11) ◽  
pp. 4567-4577 ◽  
Author(s):  
Naoki Shirafuji ◽  
Satoshi Takahashi ◽  
Satoru Matsuda ◽  
Shigetaka Asano
Keyword(s):  
Molecular Weight ◽  
Cell Death ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Antisense Rna ◽  
Mitochondrial Gene ◽  
Neutrophilic Granulocytes ◽  
High Molecular Weight Dna ◽  
Tnf Α ◽  
Morphologic Changes

To identify essential molecules capable of inducing terminal morphologic maturation and cell death of myeloid progenitor cells, we isolated cDNA clones by functional expression cloning using a library constructed from all-trans retinoic acid (ATRA)-treated human promyelocytic HL-60 cells. Clones which induced morphologic changes in HL-60 cells from blastic cells to mature neutrophilic granulocytes were selected. The isolated positive cDNA clone was demonstrated to encode an antisense RNA for cytochrome c oxidase/serine tRNA derived from a mitochondrial gene (MARCO). When MARCO was expressed in HL-60 cells with the lac switch system, blastic cell morphology became neutrophilic after 48-hour incubation with IPTG, and cell death was observed after 3 days. Also, high molecular weight DNA fragmentation was observed after 36 hours in culture. Similar results were observed using transformants from human K562 cells and CMK cells. RT-PCR analysis revealed that MARCO was transcribed in both ATRA and TNF-α systems, and also in human blood neutrophilic granulocytes. Following transfection with cytochrome c oxidase expression plasmids, TNF-α–induced high molecular weight DNA fragmentation in U937 cells and HL-60 cells was inhibited in these transformants. These results indicate that maturational changes in hematopoietic cells and the process of cell death may be induced by mitochondrial respiratory insufficiency, and also that the mitochondrial gene MARCO may be used as one of the candidates for gene supplementation therapy for the acute leukemias.

Isostenosmylus ammirabilis sp. nov., a remarkable new species of lance lacewing (Neuroptera: Osmylidae) from the Colombian Andes

Zootaxa ◽  
2020 ◽  
Vol 4803 (3) ◽  
pp. 561-575
Author(s):  
ADRIAN ARDILA-CAMACHO ◽  
CALEB CALIFRE MARTINS ◽  
JORGE ARI NORIEGA
Keyword(s):  
New Species ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Mitochondrial Gene ◽  
Dna Barcode ◽  
Neotropical Region ◽  
Andean Region ◽  
Oxidase Subunit ◽  
Colombian Andes ◽  
South Of Brazil

Isostenosmylus Krüger, 1913 is the richest genus of Osmylidae of the Neotropical region, with 17 described species so far, which are distributed mainly in the Andean region and in the South of Brazil and Paraguay. A new remarkable Colombian species of Isostenosmylus—I. ammirabilis sp. nov.—is herein described and illustrated. DNA barcode of mitochondrial gene cytochrome c oxidase subunit I (COI) for this species is also provided. Taxonomic keys for the genus are updated. 

Abstract 15546: Loss of Mitochondrial UCP3-Cytochrome c Oxidase Complexes Underlies Maladaptive Autophagy and Cardiac Failure in Anthracycline Cardiotoxicity

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Rimpy Dhingra ◽  
Victoria Margulets ◽  
Davindar Jassal ◽  
Gerald Dorn ◽  
Lorrie A Kirshenbaum
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Cardiac Failure ◽  
Uncoupling Protein ◽  
Mitochondrial Morphology ◽  
Necrotic Cell Death ◽  
Mitochondrial Targeting ◽  
Necrotic Cell ◽  
Anthracycline Cardiotoxicity

Doxorubicin is known for its cardiotoxic effects and inducing cardiac failure. Herein we demonstrate a novel signaling pathway that functionally links activation and preferential mitochondrial targeting of Bnip3 to doxorubicin cardiotoxicity. Perturbations to mitochondria including increased calcium, ROS, loss of αΨm and mPTP opening were observed in cardiac myocytes treated with doxorubicin. This coincided with a decline in maximal respiratory capacity, loss of respiratory chain complexes of uncoupling protein 3 (UCP3) and cytochrome c oxidase complex IV subunit 1, (COX) and cell viability. Impaired mitochondrial function was accompanied by an accumulated increase in autophagosomes and necrosis demonstrated by increase release of LDH, cTnT and loss of nuclear High Mobility Group Protein 1 (HMGB-1) immunoreactivity. Interestingly, pharmacological or genetic inhibition of autophagy with 3-methyl adenine (3-MA), or Atg7 knock-down suppressed necrotic cell death induced by doxorubicin. Conversely, loss of function of Bnip3 or mutations of Bnip3 defective for mitochondrial targeting restored UCP3-COX complexes, mitochondrial respiratory integrity and suppressed necrotic cell death induced by doxorubicin. Finally, mice germ-line deficient for Bnip3 were resistant to the cytotoxic effects of doxorubicin displaying mitochondrial morphology, cardiac function and survival rates comparable to vehicle treated control mice. To our knowledge the findings of the present study provide the first direct evidence that doxorubicin triggers maladaptive autophagy and necrotic cell death of ventricular myocytes by a mechanism mutually dependent and obligatorily linked to Bnip3. Hence, therapeutic interventions to selectively inhibit Bnip3 may prove beneficial in suppressing mitochondrial injury and heart failure in cancer patients undergoing doxorubicin treatment.

Abstract 24: Bnip3 Provokes ROS Production and Maladaptive Autophagy by Displacing Uncoupling Protein3 (UCP3) From Cytochrome c Oxidase of Respiration Chain Complex in Cardiotoxicity

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Rimpy Dhingra ◽  
Victoria Margulets ◽  
Davinder Jassal ◽  
Gerald Dorn II ◽  
Lorrie A. Kirshenbaum
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Cardiac Myocytes ◽  
Mitochondrial Function ◽  
Uncoupling Protein ◽  
Mitochondrial Morphology ◽  
Necrotic Cell Death ◽  
Ros Production ◽  
Necrotic Cell

Doxorubicin is known for its cardiotoxic effects and inducing cardiac failure, however, the underlying mechanisms remain cryptic. Earlier we established the inducible - death protein, Bcl-2-like Nineteen- Kilodalton- Interacting - Protein 3 (Bnip3) to be crucial for disrupting mitochondrial function and inducing cell death of cardiac myocytes. Whether Bnip3 underlies cardiotoxic effects of doxorubicin toxicity is unknown. Herein we demonstrate a novel signaling pathway that functionally links activation and preferential mitochondrial targeting of Bnip3 to the cardiotoxic properties of doxorubicin. Perturbations to mitochondria including increased calcium loading, ROS, loss of αΨm and mPTP opening were observed in cardiac myocytes treated with doxorubicin. In mitochondria, Bnip3 forms strong association with Cytochrome c oxidase subunit1 (COX1) of respiratory chain and displaces uncoupling protein 3 (UCP3) resulting in increased ROS production, decline in maximal and reserved respiration capacity and cell viability. Impaired mitochondrial function was accompanied by an accumulated increase in autophagosomes and necrosis demonstrated by increase release of LDH, cTnT and loss of nuclear High Mobility Group Protein 1 (HMGB-1) immunoreactivity. Interestingly, pharmacological or genetic inhibition of autophagy with 3-methyl adenine (3-MA), or Atg7 knock-down suppressed necrotic cell death induced by doxorubicin. Loss of function of Bnip3 restored UCP3-COX complexes, mitochondrial respiratory integrity and abrogated necrotic cell death induced by doxorubicin. Mice germ-line deficient for Bnip3 were resistant to doxorubicin cardiotoxicity displaying normal mitochondrial morphology, cardiac function and survival rates comparable to vehicle treated mice. The findings of the present study demonstrate that doxorubicin provokes maladaptive autophagy and necrotic cell death of ventricular myocytes that is mutually dependent and obligatorily linked to Bnip3.

scholarly journals Using DNA barcodes to assess identity and diversity of Dendropsophus minutus: Failure?

Zootaxa ◽  
2008 ◽  
Vol 1691 (1) ◽  
pp. 67 ◽  
Author(s):  
M. ALEX SMITH
Keyword(s):  
Cytochrome C ◽  
Small Group ◽  
Cytochrome C Oxidase ◽  
Species Identification ◽  
Mitochondrial Gene ◽  
Dna Barcode ◽  
Gene Region ◽  
Dna Barcodes ◽  
Taxonomic Groups

The 5' end (Folmer or Barcode region) of cytochrome c oxidase 1 (CO1) has been proposed as the gene region of choice for a standardized animal DNA barcode (Hebert et al. 2003). Concerns have been raised regarding the decision to utilize this particular mitochondrial gene region as a barcode. Nevertheless, widely divergent taxonomic groups have reported success using CO1 for both species identification and discovery. The utility of CO1 for barcoding amphibians was raised early on (Vences, et al. 2005) and concerns for this group were reported widely (Waugh 2007)—although some considered that the reporting of the concerns outstripped the data that had been analyzed at that point (Smith et al. 2008). Indeed, our analysis of CO1 for a small group of Holarctic amphibians was neither more difficult to generate nor to analyze than for other groups where we have utilized the technique.

Mitochondrial DNA replication and transcription are dissociated during embryonic cardiac hypertrophy

1991 ◽  
Vol 261 (6) ◽  
pp. C1091-C1098 ◽  
Author(s):  
J. M. Kennedy ◽  
S. R. Lobacz ◽  
S. W. Kelley
Keyword(s):  
Mitochondrial Dna ◽  
Cytochrome C ◽  
Cardiac Hypertrophy ◽  
Cytochrome C Oxidase ◽  
Oxidase Activity ◽  
Citrate Synthase ◽  
Incubation Temperature ◽  
Mitochondrial Gene ◽  
Gene Replication ◽  
Mitochondrial Dna Copy Number

Cardiac hypertrophy was produced in embryonic chicks by decreasing the incubation temperature from 38 degrees C to 32 degrees C on day 11. Increases in ventricular protein, RNA, and DNA support the cardiac enlargement. Cytochrome-c oxidase activity and citrate synthase activity were depressed in hypothermic ventricles by 63% and 56%, respectively. No significant differences were seen in enzyme activities in pectoralis muscles. The involvement of mitochondrial gene replication and transcription was evaluated using a cDNA clone for the mitochondrially encoded subunit III of cytochrome-c oxidase (CO III). Quantitative slot-blot analysis demonstrated that the relative CO III mRNA concentration was reduced in hypothermic ventricles. In contrast, the relative mitochondrial DNA concentration was increased in hypothermic ventricles. Taken together, these data indicate that a hypothermia-induced decrease in cytochrome-c oxidase activity is associated with a decrease in CO III mRNA, which is not coupled to a decrease in the mitochondrial DNA copy number. This dissociation of mitochondrial gene replication and transcription may provide a useful model for examining the regulation of mitochondrial biogenesis.

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