Caspase 3 regulates phosphatidylserine externalization and phagocytosis of oxidatively stressed erythrocytes

Mandal, Debabrata; Moitra, Prasun; Saha, Samiran; Basu, Joyoti

doi:10.1016/s0014-5793(02)02294-9

Cited by 166 publications

(137 citation statements)

References 21 publications

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“…This suggested that • OH-induced PS exposure was caspase-dependent in carp erythrocytes. This is in accordance with the report that oxidative stress induces death receptors (Fas) with subsequent caspase-8 and caspase-3 activation that triggers loss of aminophospholipid translocase activity with subsequent PS externalization in human erythrocytes [92,93]. The caspases-involved PS exposure may be closely associated with intracellular ROS and cytochrome c in fish erythrocyte.…”

Section: • Oh-induced Apoptosis In Fish Erythrocytessupporting

confidence: 91%

The metabolites of glutamine prevent hydroxyl radical-induced apoptosis through inhibiting mitochondria and calcium ion involved pathways in fish erythrocytes

Jiang

Liu

et al. 2016

Free Radical Biology and Medicine

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a b s t r a c tThe present study explored the apoptosis pathways in hydroxyl radicals ( • OH)-induced carp erythrocytes. Carp erythrocytes were treated with the caspase inhibitors in physiological carp saline (PCS) or Ca 2 þ -free PCS in the presence of 40 μM FeSO 4 /20 μM H 2 O 2 . The results showed that the generation of reactive oxygen species (ROS), the release of cytochrome c and DNA fragmentation were caspase-dependent, and Ca 2 þ was involved in calpain activation and phosphatidylserine (PS) exposure in • OH-induced carp erythrocytes. Moreover, the results suggested that caspases were involved in PS exposure, and Ca 2 þ was involved in DNA fragmentation in • OH-induced fish erythrocytes. These results demonstrated that there might be two apoptosis pathways in fish erythrocytes, one is the caspase and cytochrome c-dependent apoptosis that is similar to that in mammal nucleated cells, the other is the Ca 2 þ -involved apoptosis that was similar to that in mammal non-nucleated erythrocytes. So, fish erythrocytes may be used as a model for studying oxidative stress and apoptosis in mammal cells. Furthermore, the present study investigated the effects of glutamine (Gln)'s metabolites [alanine (Ala), citrulline (Cit), proline (Pro) and their combination (Ala 10 Pro 4 Cit 1 )] on the pathways of apoptosis in fish erythrocytes. The results displayed that Ala, Cit, Pro and Ala 10 Pro 4 Cit 1 effectively suppressed ROS generation, cytochrome c release, activation of caspase-3, caspase-8 and caspase-9 at the physiological concentrations, prevented Ca 2 þ influx, calpain activation, PS exposure, DNA fragmentation and the degradation of the cytoskeleton and oxidation of membrane and hemoglobin (Hb) and increased activity of anti-hydroxyl radical (AHR) in • OH-induced carp erythrocytes. Ala 10 Pro 4 Cit 1 produced a synergistic effect of inhibited oxidative stress and apoptosis in fish erythrocytes. These results demonstrated that Ala, Cit, Pro and their combination can protect mammal erythrocytes and nucleated cells against oxidative stress and apoptosis. The studies supported the use of Gln, Ala, Cit and Pro as oxidative stress and apoptosis inhibitors in mammal cells and the hypothesis that the inhibited effects of Gln on oxidative stress and apoptosis are at least partly dependent on that of its metabolites in mammalian.

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Section: • Oh-induced Apoptosis In Fish Erythrocytessupporting

confidence: 91%

The metabolites of glutamine prevent hydroxyl radical-induced apoptosis through inhibiting mitochondria and calcium ion involved pathways in fish erythrocytes

Jiang

Liu

et al. 2016

Free Radical Biology and Medicine

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“…Previous studies have shown that excessive outer leaflet exposure of PtdSer on erythrocytes can be blocked comparatively by pretreatment with a caspase-3 inhibitor (Mandal et al, 2002). Additionally, loss of flippase activity was blocked after pretreatment with the same caspase-3 inhibitor prior to oxidation (Mandal et al, 2002).…”

Section: Discussionmentioning

confidence: 91%

“…Additionally, caspases are critically involved in PtdSer externalization and apoptosis (Mandal et al, 2002;Nicholson, 1999). Activated caspase-3 is found only in cells undergoing apoptosis, and consists of p18 (amino acids 29-175; 20 kDa) and p12 subunits (amino acids 176-277; 12 kDa) (Nicholson et al, 1995), which are derived from the 32 kDa pro-enzyme (pro-caspase-3).…”

Section: Discussionmentioning

confidence: 99%

“…The process of PtdSer externalization leading to asymmetric collapse and apoptosis under oxidative stress conditions is relatively dependent on the activation of caspase-3, which is also associated with impairment of flippase activity (Mandal et al, 2002;Martin et al, 1996;Vanags et al, 1996). Previous studies have shown that excessive outer leaflet exposure of PtdSer on erythrocytes can be blocked comparatively by pretreatment with a caspase-3 inhibitor (Mandal et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Activated caspase-3 immunoreactivity has been detected in both neurons and astrocytes and found elevated in frontotemporal dementia (Su et al, 2000) and AD (Su et al, 2001). PtdSer exposure due to apoptosis has been found to occur downstream of caspase activation in some cell types (Mandal et al, 2002;Martin et al, 1996;Vanags et al, 1996); in non-neuronal cells like human erythrocytes, caspase activation is associated with loss of aminophospholipid translocase activity and subsequent PtdSer externalization (Mandal et al, 2005). Amnestic mild cognitive impairment (MCI) is considered a transition point between normal cognitive aging and dementia or probable AD (Petersen et al, 1999;Winblad et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Loss of phospholipid asymmetry and elevated brain apoptotic protein levels in subjects with amnestic mild cognitive impairment and Alzheimer disease

Lange

Cenini

Piroddi

et al. 2008

Neurobiology of Disease

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Oxidative stress, a hallmark of Alzheimer disease (AD), has been shown to induce lipid peroxidation and apoptosis disrupting cellular homeostasis. Normally, the aminophospholipid phosphatidylserine (PtdSer) is asymmetrically distributed on the cytosolic leaflet of the lipid bilayer. Under oxidative stress conditions, asymmetry is altered, characterized by the appearance of PtdSer on the outer leaflet, to initiate the first stages of an apoptotic process. PtdSer asymmetry is actively maintained by the ATP-dependent translocase flippase, whose function is inhibited if covalently bound by lipid peroxidation products, 4-hydroxynonenal (HNE) and acrolein, within the membrane bilayer in which they are produced. Additionally, pro-apoptotic proteins Bax and caspase-3 have been implemented in the oxidative modification of PtdSer resulting in subsequent asymmetric collapse, while antiapoptotic protein Bcl-2 has been found to prevent this process.The current investigation focused on detection of PtdSer on the outer leaflet of the bilayer in synaptosomes from brain of subjects with AD and amnestic mild cognitive impairment (MCI), as well as expression levels of apoptosis-related proteins Bcl-2, Bax, and caspase-3. Fluorescence and Western blot analysis suggest PtdSer exposure on the outer leaflet is significantly increased in brain from subjects with MCI and AD contributing to early apoptotic elevation of pro-and anti-apoptotic proteins and finally neuronal loss. MCI is considered a possible transition point between normal cognitive aging and probable AD. Brain from subjects with MCI is reported to have increased levels of tissue oxidation; therefore, the results of this study could mark the progression of patients with MCI into AD. This study contributes to a model of apoptosis-specific oxidation of phospholipids consistent with the notion that PtdSer exposure is required for apoptotic-cell death.

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Membrane Lipid Asymmetry in Aging and Apoptosis

Balasubramanian

Schroit

2011

Transmembrane Dynamics of Lipids

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Caspase 3 regulates phosphatidylserine externalization and phagocytosis of oxidatively stressed erythrocytes

Cited by 166 publications

References 21 publications

The metabolites of glutamine prevent hydroxyl radical-induced apoptosis through inhibiting mitochondria and calcium ion involved pathways in fish erythrocytes

The metabolites of glutamine prevent hydroxyl radical-induced apoptosis through inhibiting mitochondria and calcium ion involved pathways in fish erythrocytes

Loss of phospholipid asymmetry and elevated brain apoptotic protein levels in subjects with amnestic mild cognitive impairment and Alzheimer disease

Membrane Lipid Asymmetry in Aging and Apoptosis

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