Antibodies to Recoverin Induce Apoptosis of Photoreceptor and Bipolar Cellsin vivo

Adamus, Grażyna; Machnicki, Michał; Elerding, Heather; Sugden, Brad; Blocker, Y.; Fox, Donald A.

doi:10.1006/jaut.1998.0221

Cited by 116 publications

(88 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Results from several studies suggest that elevated rod photoreceptor [Ca 2ϩ ] plays a key role in the process of apoptotic rod cell death in humans and animals during inherited retinal degenerations, retinal diseases and injuries, and chemical exposure. These include patients with retinitis pigmentosa and cancer-associated retinopathy (9,10), lead-exposed rats (11)(12)(13), retinal degeneration mice (13,14), rats injected with anti-recoverin monoclonal antibodies (15), rats with hypoxic-ischemic injury (16), and rats with light induced damage (17).…”

mentioning

confidence: 99%

Lead and Calcium Produce Rod Photoreceptor Cell Apoptosis by Opening the Mitochondrial Permeability Transition Pore

Poblenz

Medrano

et al. 2000

Journal of Biological Chemistry

Self Cite

215

151

View full text Add to dashboard Cite

Calcium overload is suggested to play a fundamental role in the process of rod apoptosis in chemical-induced and inherited retinal degenerations. However, this hypothesis has not been tested directly. We developed an in vitro model utilizing isolated rat retinas to determine the mechanisms underlying Ca Apoptosis is an active mode of cell death that is induced by a variety of physiological and pathological stimuli. Convergent evidence suggests that mitochondria and caspases play a central and fundamental role in the effector or executioner phase of apoptosis (1). Early during the effector phase, the mitochondrial permeability transition pore (PTP), 1 a megachannel in the inner mitochondrial membrane, is opened by a variety of apoptotic inducers such as elevated matrix Ca 2ϩ , pro-oxidants, and thiol-reactive agents (1-3). This leads to mitochondrial depolarization (decrease in ⌬⌿ m ) and subsequently to the release of cytochrome c and/or apoptosis-inducing factor from mitochondria to cytosol or nuclei (1, 4, 5). Caspases are activated, which cleave downstream death substrates and activate endonucleases that cleave genomic DNA into fragments resulting in the apoptotic nuclear morphology (6, 7). The opening of the mitochondrial PTP and the apoptotic process can be inhibited by a diverse group of agents such as Bcl-2, Bcl-x L , bongkrekic acid, and CsA (1).Sustained increases in intracellular [Ca 2ϩ ] trigger apoptosis in a diverse array of in vivo and in vitro systems (1, 8). Results from several studies suggest that elevated rod photoreceptor [Ca 2ϩ ] plays a key role in the process of apoptotic rod cell death in humans and animals during inherited retinal degenerations, retinal diseases and injuries, and chemical exposure. These include patients with retinitis pigmentosa and cancer-associated retinopathy (9, 10), lead-exposed rats (11-13), retinal degeneration mice (13,14), rats injected with anti-recoverin monoclonal antibodies (15), rats with hypoxic-ischemic injury (16), and rats with light induced damage (17).Several neurotoxic heavy metals, transition metals, and organometals produce neuronal apoptosis in whole animals and cultured cells (11, 12, 18 -25). For example, low to moderate level Pb 2ϩ exposure produces apoptotic rod and bipolar cell death in developing and adult rats (11,12) and apoptotic neuronal cell death in primary cultured cells (23,24). Similarly, Cu 2ϩ and methyl mercury produce apoptosis in the developing and mature olfactory epithelium and cerebellum, respectively (18,22). Although the molecular mechanisms underlying the apoptosis induced by these different metals are unknown, there are two possible, though not mutually exclusive, triggering mechanisms: one is Ca 2ϩ overload and the other is the generation of ROS. Both in vivo and in vitro lead exposure increase rod and retinal intracellular [Ca 2ϩ ] during cell death (26, 27). Hg 2ϩ , tributyltin, and methyl mercury also cause Ca 2ϩ overload in cultured neuronal cells prior to cell death (19,20,28). Moreover, Hg 2ϩ , Mn 2ϩ , Cu 2ϩ...

show abstract

mentioning

confidence: 99%

Lead and Calcium Produce Rod Photoreceptor Cell Apoptosis by Opening the Mitochondrial Permeability Transition Pore

Poblenz

Medrano

et al. 2000

Journal of Biological Chemistry

Self Cite

215

151

View full text Add to dashboard Cite

show abstract

“…Such penetration has been associated with functional changes that may differ according to the phase of the cell cycle or state of activation of the particular cell [177,181,188]. Also antibody has been shown to lead to apoptosis of the transfected cells [181,186,187,189].…”

Section: Pathogenic Effects Of Autoantibodies To Intracellular Antigensmentioning

confidence: 99%

The Role of Pathogenic Autoantibodies in Autoimmunity

Rowley

Whittingham

2015

Antibodies

View full text Add to dashboard Cite

Abstract:The serological presence of autoantibodies is diagnostic of autoimmunity, and these autoantibodies may be present for many years before the presentation of autoimmune disease (AID). Although a pathogenic role has been demonstrated for various autoantibodies reactive with cell surface and extracellular autoantigens, studies using monoclonal antibodies (mAb) show not all antibodies in the polyclonal response are pathogenic. Differences depend on Fab-mediated diversity in epitope specificity, Fc-mediated effects based on immunoglobulin (Ig) class and subclass, activation of complement, and the milieu in which the reaction occurs. These autoantibodies often occur in organ-specific AID and this review illustrates their pathogenic and highly specific effects. The role of autoantibodies associated with intracellular antigens is less clear. In vitro they may inhibit or adversely affect well-defined intracellular biochemical pathways, yet, in vivo they are separated from their autoantigens by multiple cellular barriers. Recent evidence that Ig can traverse cell membranes, interact with intracellular proteins, and induce apoptosis has provided new evidence for a pathogenic role for such autoantibodies. An understanding of how autoantibodies behave in the polyclonal response and their role in pathogenesis of AID may help identify populations of culprit B-cells and selection of treatments that suppress or eliminate them.

show abstract

“…Recoverin is known to play an important role in the light and dark adaptation by regulating rhodopsin phosphorylation and dephosphorylation in a Ca 2+ -dependent manner (Kawamura 1991;Ohguro et al 1996). As a mechanism for the apoptotic cell death of photoreceptor cells observed in CAR, it has been postulated that anti-recoverin antibody generated by unknown mechanisms in some cancer patients penetrates into the photoreceptor cells via the peripheral circulation and causes misregulation of the phototransduction pathway by blocking recoverin function (Adamus et al 1998;Maeda et al 2001b). In the initial step of CAR pathogenesis, several studies suggested that aberrant expression of retina-specific recoverin, serving as a shared antigen between tumor cells and retina, was critical since such aberrant expression of recoverin had been identified in tumor cells in CAR patients but not in non-CAR cancerous patients (Polans et al 1995;Matsubara et al 1996;Yamaji et al 1996).…”

confidence: 99%

Clinicopathological Features of Gastric Cancer Cases and Aberrantly Expressed Recoverin

Ohguro

Odagiri

Miyagawa

et al. 2004

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Antibodies to Recoverin Induce Apoptosis of Photoreceptor and Bipolar Cellsin vivo

Cited by 116 publications

References 0 publications

Lead and Calcium Produce Rod Photoreceptor Cell Apoptosis by Opening the Mitochondrial Permeability Transition Pore

Lead and Calcium Produce Rod Photoreceptor Cell Apoptosis by Opening the Mitochondrial Permeability Transition Pore

The Role of Pathogenic Autoantibodies in Autoimmunity

Clinicopathological Features of Gastric Cancer Cases and Aberrantly Expressed Recoverin

Contact Info

Product

Resources

About