Mechanism of dibucaine-induced apoptosis in promyelocytic leukemia cells (HL-60)

Arita, Kayo; Utsumi, Toshihiko; Kato, Akio; Kanno, Tomoko; Kobuchi, Hirotsugu; Inoue, Bunji; Akiyama, Jitsuo; Utsumi, Kozo

doi:10.1016/s0006-2952(00)00406-8

Cited by 60 publications

(47 citation statements)

References 36 publications

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“…In HL-60 cells, polyunsaturated fatty acids inhibit their growth and induce apoptosis by releasing cytochrome c from mitochondria by two distinct mechanisms: membrane depolarization-dependent and -independent (80). It has been reported recently that micromolar arachidonic acid induces permeability transition in isolated rat liver mitochondria and in hepatoma cells (81).…”

Section: Discussionmentioning

confidence: 99%

Rat Brain Cortex Mitochondria Release Group II Secretory Phospholipase A2 under Reduced Membrane Potential

Macchioni¹,

Corazzi²,

Nardicchi³

et al. 2004

Journal of Biological Chemistry

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Activation of brain mitochondrial phospholipase(s) A 2 (PLA 2 ) might contribute to cell damage and be involved in neurodegeneration. Despite the potential importance of the phenomenon, the number, identities, and properties of these enzymes are still unknown. Here, we demonstrate that isolated mitochondria from rat brain cortex, incubated in the absence of respiratory substrates, release a Ca 2؉ -dependent PLA 2 having biochemical properties characteristic to secreted PLA 2 (sPLA 2 ) and immunoreacting with the antibody raised against recombinant type IIA sPLA 2 (sPLA 2 -IIA). Under identical conditions, no release of fumarase in the extramitochondrial medium was observed. The release of sPLA 2 from mitochondria decreases when mitochondria are incubated in the presence of respiratory substrates such as ADP, malate, and pyruvate, which causes an increase of transmembrane potential determined by cytofluorimetric analysis using DiOC 6 (3) as a probe. The treatment of mitochondria with the uncoupler carbonyl cyanide 3-chlorophenylhydrazone slightly enhances sPLA 2 release. The increase of sPLA 2 specific activity after removal of mitochondrial outer membrane indicates that the enzyme is associated with mitoplasts. The mitochondrial localization of the enzyme has been confirmed by electron microscopy in U-251 astrocytoma cells and by confocal laser microscopy in the same cells and in PC-12 cells, where the structurally similar isoform type V-sPLA 2 has mainly nuclear localization. In addition to sPLA 2 , mitochondria contain another phospholipase A 2 that is Ca 2؉ -independent and sensitive to bromoenol lactone, associated with the outer mitochondrial membrane. We hypothesize that, under reduced respiratory rate, brain mitochondria release sPLA 2 -IIA that might contribute to cell damage.

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Section: Discussionmentioning

confidence: 99%

Rat Brain Cortex Mitochondria Release Group II Secretory Phospholipase A2 under Reduced Membrane Potential

Macchioni¹,

Corazzi²,

Nardicchi³

et al. 2004

Journal of Biological Chemistry

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“…However, bupivacaine was shown to have a more potent cytotoxic effect than ropivacaine on the same cell types [6]. Other local anesthetics appear to have similar effects on various cell types [9][10][11][12][13][14]. Prilocaine was found to induce apoptosis in mouse and human osteoblastic cells [11] and lidocaine was shown to inhibit the proliferation of normal human fibroblasts, endothelial cells and keratinocytes [12], while enhancing bleomycin A 2 cytotoxicity and DNA strand breakage in murine leukemia cells and human head and neck carcinoma cells [13] and imparing corneal wound healing [14].…”

Section: Discussionmentioning

confidence: 99%

“…Prilocaine was found to induce apoptosis in mouse and human osteoblastic cells [11] and lidocaine was shown to inhibit the proliferation of normal human fibroblasts, endothelial cells and keratinocytes [12], while enhancing bleomycin A 2 cytotoxicity and DNA strand breakage in murine leukemia cells and human head and neck carcinoma cells [13] and imparing corneal wound healing [14]. Dibucaine was shown to induce apoptosis in a neuroblastoma cell line [9] and in HL-60 [10] cells through activation of various caspases in conjunction with the release of cytochrome c from mitochondria induced by a processed product of Bid and depolarization of the mitochondrial membrane potential [10]. Although at certain concentrations ropivacaine induced apoptosis of HaCaT cells, we do not know if this was due to Bid cleavage and cytochrome c release.…”

Section: Discussionmentioning

confidence: 99%

“…There are relatively fewer in vitro studies investigating the effects of local anesthetics on cell proliferation, apoptosis and gene expression [9][10][11][12][13][14]. It was reported that ropivacaine was shown to inhibit the proliferation of nontransformed cultured adult human fibroblasts, endothelial cells, keratinocytes [12] and primary rat fibroblast [6], as well as that of the transformed monkey kidney Vero cells [6] and human colon cell lines [15].…”

Section: Introductionmentioning

confidence: 99%

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Ectopic expression of clusterin/apolipoprotein J or Bcl-2 decreases the sensitivity of HaCaT cells to toxic effects of ropivacaine

et al. 2004

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Local anesthetics inhibit cell proliferation and induce apoptosis in various cell types. Ropivacaine, a unique, novel tertiary amine-type anesthetic, was shown to inhibit the proliferation of several cell types including keratinocytes. We found that Ropivacaine could inhibit the proliferation and induce apoptosis in an immortalized human keratinocyte line, HaCaT, in a dose-and time-dependent manner and with the deprivation of serum. The dose-dependent induction of apoptosis by ropivacaine was demonstrated by DNA fragmentation analysis and the proteolytic cleavage of a caspase-3 substrate -poly (ADP-ribose) polymerase (PARP). In addition, ropivacaine downregulated the expression of clusterin/ apoliporotein J, a protein with anti-apoptotic properties, in a dose-dependent manner, which well correlated with the induction of apoptosis of HaCaT cells. To investigate the role of clusterin/apoliporotein J in ropivacaine-induced apoptosis, HaCaT cells overexpressing clusterin/apoliporotein J were generated and compared to cells expressing the well established anti-apoptotic Bcl-2 protein. Ectopic overexpression of the secreted form of clusterin/apoliporotein J or Bcl-2 decreased the sensitivity of HaCaT cells to toxic effects of ropivacaine as demonstrated by DNA fragmentation, the proteolytic cleavage of PARP and by a reduction in procaspase-3 expression. Furthermore, the downregulation of endogenous clusterin/apolipoprotein J levels by ropivacaine suggested that this might be one mechanism by which ropivacaine induced cell death in HaCaT cells. In conclusion, the ability of ropivacaine to induce antiproliferative responses and to suppress the expression of the anti-apoptotic protein clusterin/apolipoprotein J, combined with previously reported anti-inflammatory activity and analgesic property of the drug, suggests that ropivacaine may have potential utility in the local treatment of tumors.

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“…Mitochondrial swelling and oxidation of membrane protein thiol groups were associated with the activation of PTP, which was inhibited by the local anesthetic 52 . DNA fragmentation and DNA "ladder" formation, a typical feature for apoptosis, were induced by dibucaine with half-maximal concentration of 100 µM, and these effects were completely prevented by the unspecific caspase inhibitor z-Val-Ala-Asp-(OMe)-fluoromethylketone, thereby implicating caspase activation in the process 53 . Lidocaine-induced apoptosis was also associated with the mitochondrial caspase pathways 54 .…”

Section: Local Anesthetics and Mitochondrionmentioning

confidence: 99%

A cardiolipina é o alvo da cardiotoxicidade dos anestésicos locais?

Shen¹,

Xu²,

Qian³

et al. 2010

Rev. Bras. Anestesiol.

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Is Cardiolipin the Target of Local Anesthetic Cardiotoxicity?Background and objectives: Local anesthetics are used broadly to prevent or reverse acute pain and treat symptoms of chronic pain. Local anesthetic-induced cardiotoxic reaction has been considered the accidental event without currently effective therapeutic drugs except for recently reported intralipid infusion whose possible mechanism of action is not well known. Contents:Cardiolipin, an anionic phospholipid, plays a key role in determining mitochondrial respiratory reaction, fatty acid metabolism and cellular apoptosis. Mitochondrial energy metabolism dysfunction is suggested as associated with local anesthetic cardiotoxicity, from an in vitro study report that the local anesthetic cardiotoxicity may be due to the strong electrostatic interaction of local anesthetics and cardiolipin in the mitochondria membrane, although there is a lack for experimental evidence. Herein we hypothesized that local anesthetic-cardiolipin interactions were the major determinant of local anesthetic-associated cardiotoxic reaction, established by means of theoretic and structural biological methods. This interacting model would give an insight on the underlying mechanism of local anesthetic cardiotoxicity and provide clues for further in depth research on designing preventive drugs for such inadvertent accidence in routine clinical practice. Conclusions:The interaction between local anesthetic and mitochondrial cardiolipin may be the underlying mechanism for cardiotoxicity affecting its energy metabolism and electrostatic status.

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Mechanism of dibucaine-induced apoptosis in promyelocytic leukemia cells (HL-60)

Cited by 60 publications

References 36 publications

Rat Brain Cortex Mitochondria Release Group II Secretory Phospholipase A2 under Reduced Membrane Potential

Rat Brain Cortex Mitochondria Release Group II Secretory Phospholipase A2 under Reduced Membrane Potential

Ectopic expression of clusterin/apolipoprotein J or Bcl-2 decreases the sensitivity of HaCaT cells to toxic effects of ropivacaine

A cardiolipina é o alvo da cardiotoxicidade dos anestésicos locais?

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