Involvement of oxidative stress and caspase 2-mediated intrinsic pathway signaling in age-related increase in muscle cell apoptosis in mice

Braga, Melissa; Hikim, Amiya P. Sinha; Datta, Sanjit; Ferrini, Mónica G.; Brown, Danielle L.; Kovacheva, Ekaterina; González‐Cadavid, Néstor F.; Sinha‐Hikim, Indrani

doi:10.1007/s10495-008-0216-7

Cited by 116 publications

(114 citation statements)

References 63 publications

(113 reference statements)

Supporting

Mentioning

107

Contrasting

Unclassified

Order By: Relevance

“…During muscle cell apoptosis in age-related sarcopenia, the increase in HNE generation leads to anti-apoptotic protein inactivation and JNK and caspase 2/9 activation. 81 The same observation was made in the RKO colon cancer cell line 82 and in the PC12 neuronal cell line. 83 Figure 2 The early events upstream of mitochondria targeting are diverse and are highly dependent on the initial stimulus.…”

Section: Hne: a Serial Killersupporting

confidence: 59%

Cell death and diseases related to oxidative stress:4-hydroxynonenal (HNE) in the balance

et al. 2013

View full text Add to dashboard Cite

During the last three decades, 4-hydroxy-2-nonenal (HNE), a major a,b-unsaturated aldehyde product of n-6 fatty acid oxidation, has been shown to be involved in a great number of pathologies such as metabolic diseases, neurodegenerative diseases and cancers. These multiple pathologies can be explained by the fact that HNE is a potent modulator of numerous cell processes such as oxidative stress signaling, cell proliferation, transformation or cell death. The main objective of this review is to focus on the different aspects of HNE-induced cell death, with a particular emphasis on apoptosis. HNE is a special apoptotic inducer because of its abilities to form protein adducts and to propagate oxidative stress. It can stimulate intrinsic and extrinsic apoptotic pathways and interact with typical actors such as tumor protein 53, JNK, Fas or mitochondrial regulators. At the same time, due to its oxidant status, it can also induce some cellular defense mechanisms against oxidative stress, thus being involved in its own detoxification. These processes in turn limit the apoptotic potential of HNE. These dualities can imbalance cell fate, either toward cell death or toward survival, depending on the cell type, the metabolic state and the ability to detoxify.

show abstract

Section: Hne: a Serial Killersupporting

confidence: 59%

Cell death and diseases related to oxidative stress:4-hydroxynonenal (HNE) in the balance

et al. 2013

View full text Add to dashboard Cite

show abstract

“…The elevation of Bcl-2 detected in aged muscles may be interpreted as a compensatory attempt to limit myonuclear loss. Alternatively, the increased serine phosphorylation and subsequent inactivation of Bcl-2 recently reported in old mice [52] might abolish the antiapoptotic activity of this molecule despite elevated expression [53]. …”

Section: The Involvement Of Apoptosis In the Pathogenesis Of Sarcopeniamentioning

confidence: 99%

“…Elevated cytosolic levels of cytochrome c have been detected in the skeletal muscle of old rats [46]. Accordingly, levels of Apaf-1 [13,46,60], active caspase-9 content [52,54,60], and caspase-9 proteolytic activity [46] were also found to be higher in aged muscles compared to young controls. However, other studies did not observe increases in cytosolic cytochrome c and/or caspase-9 expression in skeletal muscles of old rats [12,13,18,49].…”

Section: The Involvement Of Apoptosis In the Pathogenesis Of Sarcopeniamentioning

confidence: 99%

See 1 more Smart Citation

Multiple Pathways to the Same End: Mechanisms of Myonuclear Apoptosis in Sarcopenia of Aging

Marzetti

Privitera

Simili

et al. 2010

The Scientific World JOURNAL

View full text Add to dashboard Cite

Sarcopenia, the age-related decline in muscle mass and function, represents a significant health issue due to the high prevalence of frailty and disability associated with this condition. Nevertheless, the cellular mechanisms responsible for the loss of muscle mass in old age are still largely unknown. An altered regulation of myocyte apoptosis has recently emerged as a possible contributor to the pathogenesis of sarcopenia. Studies in animal models have shown that the severity of skeletal muscle apoptosis increases over the course of aging and correlates with the degree of muscle mass and strength decline. Several apoptotic pathways are operative in aged muscles, with the mitochondria- and TNF-α-mediated pathways likely being the most relevant to sarcopenia. However, despite the growing number of studies on the subject, a definite mechanistic link between myocyte apoptosis and age-related muscle atrophy has not yet been established. Furthermore, the evidence on the role played by apoptosis in human sarcopenia is still sparse. Clearly, further research is required to better define the involvement of myocyte apoptosis in the pathogenesis of muscle loss at advanced age. This knowledge will likely help in the design of more effective therapeutic strategies to preserve muscle mass into old age, thus fostering independence of the elderly population and reducing the socioeconomic burden associated with sarcopenia.

show abstract

“…Decreases in the muscle mass of the gastrocnemius, composed of predominantly fast‐twitch fibers, are quite remarkable during aging. In contrast, the soleus muscle, composed of predominantly slow‐twitch fibers, shows less atrophy and is much less affected during aging among humans and rodents (Braga et al., 2008; Kovacheva, Hikim, Shen, Sinha & Sinha‐Hikim, 2010; Martin et al., 2007; Sinha‐Hikim et al., 2013). This is consistent with observations indicating that fiber size decline prominently affects fast‐twitch fibers, and that slow‐twitch fibers are less affected.…”

Section: Introductionmentioning

confidence: 99%

Comparative proteomic profiling reveals a role for Cisd2 in skeletal muscle aging

Huang¹,

Shen²,

Wu³

et al. 2017

Aging Cell

View full text Add to dashboard Cite

SummarySkeletal muscle has emerged as one of the most important tissues involved in regulating systemic metabolism. The gastrocnemius is a powerful skeletal muscle composed of predominantly glycolytic fast‐twitch fibers that are preferentially lost among old age. This decrease in gastrocnemius muscle mass is remarkable during aging; however, the underlying molecular mechanism is not fully understood. Strikingly, there is a ~70% decrease in Cisd2 protein, a key regulator of lifespan in mice and the disease gene for Wolfram syndrome 2 in humans, within the gastrocnemius after middle age among mice. A proteomics approach was used to investigate the gastrocnemius of naturally aged mice, and this was compared to the autonomous effect of Cisd2 on gastrocnemius aging using muscle‐specific Cisd2 knockout (mKO) mice as a premature aging model. Intriguingly, dysregulation of calcium signaling and activation of UPR/ER stress stand out as the top two pathways. Additionally, the activity of Serca1 was significantly impaired and this impairment is mainly attributable to irreversibly oxidative modifications of Serca. Our results reveal that the overall characteristics of the gastrocnemius are very similar when naturally aged mice and the Cisd2 mKO mice are compared in terms of pathological alterations, ultrastructural abnormalities, and proteomics profiling. This suggests that Cisd2 mKO mouse is a unique model for understanding the aging mechanism of skeletal muscle. Furthermore, this work substantiates the hypothesis that Cisd2 is crucial to the gastrocnemius muscle and suggests that Cisd2 is a potential therapeutic target for muscle aging.

show abstract

Involvement of oxidative stress and caspase 2-mediated intrinsic pathway signaling in age-related increase in muscle cell apoptosis in mice

Cited by 116 publications

References 63 publications

Cell death and diseases related to oxidative stress:4-hydroxynonenal (HNE) in the balance

Cell death and diseases related to oxidative stress:4-hydroxynonenal (HNE) in the balance

Multiple Pathways to the Same End: Mechanisms of Myonuclear Apoptosis in Sarcopenia of Aging

Comparative proteomic profiling reveals a role for Cisd2 in skeletal muscle aging

Contact Info

Product

Resources

About