Aging-associated increase of gelsolin for apoptosis resistance

Ahn, Jongmin; Jang, Ik‐Soon; Kim, Duk-In; Cho, Kyung A.; Park, Yong Hoon; Kim, Kyung‐Tae; Kwak, Chung Sil; Park, Sang Chul

doi:10.1016/j.bbrc.2003.11.061

Cited by 33 publications

(27 citation statements)

References 34 publications

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“…30 Gelsolin levels are elevated in many senescent tissues where increased gelsolin expression is believed to be responsible for the resistance to apoptosis and to the increased susceptibility of these tissue to cancer. 31 Studies done in yeast have shown that actin functions as a sensor that links changes in the nutritional status with mitochondrial-dependent commitment to cell death. 32 A strong but as-yet-undefined link between the actin cytoskeleton and apoptosis has also been described in plant and animal cells.…”

Section: Discussionmentioning

confidence: 99%

Actin reorganization as the molecular basis for the regulation of apoptosis in gastrointestinal epithelial cells

et al. 2012

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The gastrointestinal (GI) epithelium is a rapidly renewing tissue in which apoptosis represents part of the overall homeostatic process. Regulation of apoptosis in the GI epithelium is complex with a precise relationship between cell position and apoptosis. Apoptosis occurs spontaneously and in response to radiation and cytotoxic drugs at the base of the crypts. By contrast, the villus epithelial cells are extremely resistant to apoptosis. The molecular mechanism underlying this loss of function of villus epithelial cells to undergo apoptosis shortly after their exit from the crypt is unknown. In this study we demonstrate for the first time, that deletion of two homologous actin-binding proteins, villin and gelsolin renders villus epithelial cells extremely sensitive to apoptosis. Ultrastructural analysis of the villin-gelsolin À/À double-knockout mice shows an abnormal accumulation of damaged mitochondria demonstrating that villin and gelsolin function on an early step in the apoptotic signaling at the level of the mitochondria. A characterization of functional and ligand-binding mutants demonstrate that regulated changes in actin dynamics determined by the actin severing activities of villin and gelsolin are required to maintain cellular homeostasis. Our study provides a molecular basis for the regulation of apoptosis in the GI epithelium and identifies cell biological mechanisms that couple changes in actin dynamics to apoptotic cell death.

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Section: Discussionmentioning

confidence: 99%

Actin reorganization as the molecular basis for the regulation of apoptosis in gastrointestinal epithelial cells

et al. 2012

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“…This maladaptive cardiac remodeling associated with diabetes increases cardiac muscle stiffness and may contribute to the impaired diastolic function that accompanies diabetic cardiomyopathy. Recently, it has been shown that increased levels of gelsolin, a Ca +2 dependent actin-regulatory protein [51], in heart tissue of old rats, may be partly responsible for age-related apoptosis resistance [32]. In fact, prior studies conducted in nondiabetic hearts have reported an increased sensitivity to apotosis-induction by gelsolin downregulation [32].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it has been shown that increased levels of gelsolin, a Ca +2 dependent actin-regulatory protein [51], in heart tissue of old rats, may be partly responsible for age-related apoptosis resistance [32]. In fact, prior studies conducted in nondiabetic hearts have reported an increased sensitivity to apotosis-induction by gelsolin downregulation [32]. To the best of our knowledge, this is the first study to document a reduction in the protein expression levels of gelsolin in the diabetic heart.…”

Section: Discussionmentioning

confidence: 99%

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Alterations in the diabetic myocardial proteome coupled with increased myocardial oxidative stress underlies diabetic cardiomyopathy

Hamblin

Friedman

Hill

et al. 2007

Journal of Molecular and Cellular Cardiology

113

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“…The discrepancy may be caused by age-related enhancement of cell resistance to oxidative insult. Cell aging reportedly renders human fibroblasts less susceptible to ROS-induced cell apoptosis, 51 although the mechanism responsible for resistance to apoptosis is still uncertain. Further investigations should clarify the details of age-associated changes in cell vulnerability to oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress Promotes Endothelial Cell Apoptosis and Loss of Microvessels in the Spontaneously Hypertensive Rats

Kobayashi

DeLano

Schmid‐Schönbein

2005

ATVB

116

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Objective-Endothelial cell apoptosis caused by oxidative stress may lead to the loss of microvessels (rarefaction) in hypertension. We examine here the effects of antioxidants on cell apoptosis and rarefaction. Methods and Results-The juvenile spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were treated with superoxide scavengers, Tempol or Tiron, during growth. After the treatment, oxidative stress status, endothelial cell apoptosis rate, and microvessel length density in skeletal muscle and mesentery were evaluated in comparison with age-matched controls. Untreated 16-week-old SHR had higher oxidative stress (PϽ0.01) and cell apoptosis rate (PϽ0.05) and lower microvessel length density (371Ϯ17 mm/mm 3 [PϽ0.01]) compared with age-matched WKY rats (435Ϯ15 mm/mm 3 ). In the SHR, but not in WKY rats, systemically applied antioxidants attenuated oxidative stress and cell apoptosis rate (PϽ0.05 versus untreated controls) and prevented the loss of microvessels (411Ϯ15 Key Words: arterial hypertension Ⅲ capillary Ⅲ endothelial cell apoptosis Ⅲ microvessels Ⅲ oxidative stress Ⅲ rarefaction Ⅲ superoxide A number of hypertensive animal models 1-3 and patients with essential hypertension 4 exhibit a reduction in microvessel length density in tissues such as skeletal muscle, skin, conjunctiva, and myocardium. This phenomenon, designated as structural or anatomic rarefaction, leads to an increase in peripheral vascular resistance and localized reduction in oxygen delivery to the tissue. 5 Substantial evidence indicates that microvascular rarefaction is associated with the pathogenesis of hypertension and may be accompanied by parenchymal cell death. 6,7 The disappearance of microvessels in hypertensive subjects may be a secondary event after blood pressure elevation. 8 However, recent research in man demonstrates microvascular rarefaction in pre-established stage of hypertensive subjects who still maintain near normal blood pressure. 9 In addition, the loss of microvessels is implicated in development of nonhypertensive pathologic conditions including diabetic organ failure. 10 These findings seem to suggest that factors other than elevated arterial pressure may promote the disappearance of microvessels. Accumulating evidence indicates that the increase in endothelial cell apoptosis in microvessels may cause rarefaction in hypertensive subjects, although the mechanism of enhanced cell apoptosis is still undergoing investigation. 11,12 We hypothesize that oxidative stress promotes endothelial cell apoptosis in microvessels and induces rarefaction in the spontaneously hypertensive rats (SHR). In the SHR, microvascular endothelium is exposed to enhanced oxidative stress due to an increase in xanthine-oxidase 13 and NADPH-oxidase activity 14 and/or a reduction in superoxide-dismutase activity. 15 Reactive oxygen species (ROS) modulate diverse functions and exert secondary effects on microvessels, eg, an inhibition of endothelium-dependent vasodilation 16 and a promotion of leukocyte adhesion to e...

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Aging-associated increase of gelsolin for apoptosis resistance

Cited by 33 publications

References 34 publications

Actin reorganization as the molecular basis for the regulation of apoptosis in gastrointestinal epithelial cells

Actin reorganization as the molecular basis for the regulation of apoptosis in gastrointestinal epithelial cells

Alterations in the diabetic myocardial proteome coupled with increased myocardial oxidative stress underlies diabetic cardiomyopathy

Oxidative Stress Promotes Endothelial Cell Apoptosis and Loss of Microvessels in the Spontaneously Hypertensive Rats

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