An Ultrastructural and Immunohistochemical Study of PC12 Cells During Apoptosis Induced by Serum Deprivation with Special Reference to Autophagy and Lysosomal Cathepsins.

Ohsawa, Yoshiyuki; Isahara, Kyoko; Kanamori, Shiro; Shibata, Masahiro; KAMETAKA, Satoshi; Gotow, Takahiro; Watanabe, Tsuyoshi; Kominami, Eiki; Uchiyama, Yasuo

doi:10.1679/aohc.61.395

Cited by 65 publications

(52 citation statements)

References 28 publications

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“…However, a variety of cytotoxic agents cause lysosomal damage. For example, lysosomal disruption and release of lysosomal proteases into the cytoplasm occurs during alpha-tocopheryl succinate-induced apoptosis in Jurkat T cells, 42 during serumwithdrawal-induced apoptosis in PC12 cells, 30 during naphthazarine-induced apoptosis of neonatal cardiomyocytes 31 and foreskin fibroblasts, 32 and following exposure of macrophages to O-methyl-serine dodecylamide hydrochloride. 43 In at least three of these studies lysosomal damage occurred prior to the release of cytochrome c and/ or loss of DC m .…”

Section: Discussionmentioning

confidence: 99%

Release of cytochrome c and activation of pro-caspase-9 following lysosomal photodamage involves bid cleavage

et al. 2002

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Photodynamic therapy (PDT) protocols employing lysosomal sensitizers induce apoptosis via a mechanism that causes cytochrome c release prior to loss of mitochondrial membrane potential (DC m ). The current study was designed to determine how lysosomal photodamage initiates mitochondrialmediated apoptosis in murine hepatoma 1c1c7 cells. Fluorescence microscopy demonstrated that the photosensitizer N-aspartyl chlorin e6 (NPe6) localized to the lysosomes. Irradiation of cultures preloaded with NPe6 induced the rapid destruction of lysosomes, and subsequent cleavage/activation of Bid, pro-caspases-9 and -3. Pro-caspase-8 was not activated. Release of cytochrome c occurred at about the time of Bid cleavage and preceded the loss of DC m . Extracts of purified lysosomes catalyzed the in vitro cleavage of cytosolic Bid, but not pro-caspase-3 activation. Pharmacological inhibition of cathepsin B, L and D activities did not suppress Bid cleavage or pro-caspases-9 and -3 activation. These studies demonstrate that photodamaged lysosomes trigger the mitochondrial apoptotic pathway by releasing proteases that activate Bid.

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Section: Discussionmentioning

confidence: 99%

Release of cytochrome c and activation of pro-caspase-9 following lysosomal photodamage involves bid cleavage

et al. 2002

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“…42 After washing with PBS they were incubated overnight at 48C with anti-Bcl-2 antibody diluted in PBS containing 0.05% Tween 20, and then with anti-rabbit ormouse IgG conjugated with FITC (Biomedia). Some samples were incubated with both monoclonal anti-Bcl-2 and polyclonal anti-subunit b or -porin and then with anti-mouse IgG coupled with FITC and anti-rabbit IgG with Texas Red (Biomedia) for colocalization studies.…”

Section: Immunohisto/cytochemistrymentioning

confidence: 99%

Selective localization of Bcl-2 to the inner mitochondrial and smooth endoplasmic reticulum membranes in mammalian cells

et al. 2000

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Bcl-2, an anti-apoptotic protein, is believed to be localized in the outer mitochondrial membrane, endoplasmic reticulum, and nuclear envelope. However, Bcl-2 has also been suggested as playing a role in the maintenance of mitochondrial membrane potential, indicating its possible association with the inner mitochondrial membrane. We therefore further examined the exact localization of Bcl-2 in mitochondria purified from wild-type and bcl-2-transfected PC12 cells and pre-and postnatal rat brains. Double immunostaining demonstrated that Bcl-2 was co-localized with subunit b of F 1 F 0 ATPase in the inner mitochondrial membrane. Biochemical analysis of isolated mitochondria using digitonin and trypsin suggests an association of Bcl-2 with the inner mitochondrial membrane. More interestingly, the majority of Bcl-2 disappeared from the inner membrane of mitochondria when cultured under serum deprivation. These results suggest that Bcl-2 acts as an anti-apoptotic regulator by localizing mainly to the inner mitochondrial and smooth ER membranes. Cell Death and Differentiation (2000) 7, 666 ± 674.

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“…In addition, autophagy is induced under starvation, differentiation, and normal growth control to maintain homeostasis and survival [1][2][3] ; however, it is also involved in neurodegenerative disorders and can trigger a form of programmed cell death (Type II death) distinct from apoptosis in neurons [4][5][6][7] . Accumulating evidence indicates that autophagy is activated and may be involved in the regulation of neuronal death in different animal models of ischemic brain injury, including hypoxiaischemia (HI) and global and focal ischemia [7][8][9][10][11][12][13][14][15][16][17] .…”

Section: Introductionmentioning

confidence: 99%

Death and survival of neuronal and astrocytic cells in ischemic brain injury: a role of autophagy

Zhang

2011

Acta Pharmacol Sin

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Autophagy is a highly regulated cellular mechanism that leads to degradation of long-lived proteins and dysfunctional organelles. The process has been implicated in a variety of physiological and pathological conditions relevant to neurological diseases. Recent studies show the existence of autophagy in cerebral ischemia, but no consensus has yet been reached regarding the functions of autophagy in this condition. This article highlights the activation of autophagy during cerebral ischemia and/or reperfusion, especially in neurons and astrocytes, as well as the role of autophagy in neuronal or astrocytic cell death and survival. We propose that physiological levels of autophagy, presumably caused by mild to modest hypoxia or ischemia, appear to be protective. However, high levels of autophagy caused by severe hypoxia or ischemia and/or reperfusion may cause self-digestion and eventual neuronal and astrocytic cell death. We also discuss that oxidative and endoplasmic reticulum (ER) stresses in cerebral hypoxia or ischemia and/or reperfusion are potent stimuli of autophagy in neurons and astrocytes. In addition, we review the evidence suggesting a considerable overlap between autophagy on one hand, and apoptosis, necrosis and necroptosis on the other hand, in determining the outcomes and final morphology of damaged neurons and astrocytes.

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An Ultrastructural and Immunohistochemical Study of PC12 Cells During Apoptosis Induced by Serum Deprivation with Special Reference to Autophagy and Lysosomal Cathepsins.

Cited by 65 publications

References 28 publications

Release of cytochrome c and activation of pro-caspase-9 following lysosomal photodamage involves bid cleavage

Release of cytochrome c and activation of pro-caspase-9 following lysosomal photodamage involves bid cleavage

Selective localization of Bcl-2 to the inner mitochondrial and smooth endoplasmic reticulum membranes in mammalian cells

Death and survival of neuronal and astrocytic cells in ischemic brain injury: a role of autophagy

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