Age-dependent upregulation of p53 and cytochrome c release and susceptibility to apoptosis in skeletal muscle fiber of aged rats: Role of carnitine and lipoic acid

Jayavelu, Tamilselvan; Jayaraman, G.; Sivarajan, Kumarasamy; Panneerselvam, Chinnakkannu

doi:10.1016/j.freeradbiomed.2007.08.028

Cited by 44 publications

(27 citation statements)

References 61 publications

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“…Besides alterations in the Bcl-2 rheostat, increased susceptibility towards opening of the mPTP has also been demonstrated in aged skeletal muscles [54–56]. Interestingly, elevated mitochondrial levels of CyPD relative to ANT and VDAC were detected in the gastrocnemius muscle of very old rats [18].…”

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%

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

Marzetti

Privitera

Simili

et al. 2010

The Scientific World JOURNAL

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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.

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Section: The Involvement Of Apoptosis In the Pathogenesis Of Sarcopeniamentioning

confidence: 99%

Section: The Involvement Of Apoptosis In the Pathogenesis Of Sarcopeniamentioning

confidence: 99%

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

Marzetti

Privitera

Simili

et al. 2010

The Scientific World JOURNAL

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“…It is well established that isoflurane-induced excessive Ca 2+ influx leads to apoptosis which is triggered by mitochondrial damage [21][22][23] . The damaged mitochondria then release cytochrome C to the cytosol [2] .…”

Section: Discussionmentioning

confidence: 99%

“…When cells are exposed to apoptotic stimuli, cytochrome C is rapidly released from the mitochondria into the cytosol. Cytosolic cytochrome C can further activate caspase-3 and trigger the occurrence of apoptosis [2] . Numerous studies have demonstrated that the cytochrome C release from the mitochondria to the cytoplasm is the common step for many intracellular apoptotic signaling pathways [3,4] .…”

mentioning

confidence: 99%

Isoflurane enhances the expression of cytochrome C by facilitation of NMDA receptor in developing rat hippocampal neurons in vitro

Zhao

Jin

Wang

et al. 2011

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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This study examined the effects of clinically relevant concentrations of isoflurane on the amplitude of NMDA receptor current (I(NMDA)) and the expression of cytochrome C in cultured developing rat hippocampal neurons. The hippocampi were dissected from newborn Sprague-Dawley rats. Hippocampal neurons were primarily cultured for 5 days and then treated with different concentrations of isoflurane [(0.25, 0.5, 0.75, 1 minimum alveolar concentration (MAC))]. The peak of I(NMDA) was recorded by means of the whole cell patch clamp technique. The cytochrome C level was detected by Western blotting and quantitative real-time PCR. Our results showed that isoflurane (0.25, 0.5, 0.75 and 1 MAC) potentiated the amplitude of I(NMDA) by (116 ± 8.8)%, (122 ± 11.7)%, (135 ± 14.3)% and (132 ± 14.6)%, respectively, and isoflurane increased the mRNA expression of cytochrome C in a concentration-dependent manner. The cytochrome C mRNA expression reached a maximum after 0.5 MAC isoflurane stimulation for 6 h (P<0.05). It was concluded that isoflurane enhances the expression of cytochrome C in cultured rat hippocampal neurons, which may be mediated by facilitation of NMDA receptor.

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“…A decline in mitochondrial function associated with compromised mtDNA quality during aging leads to a decrease in both the capacity and regulation of oxidative phosphorylation (Li et al, 2010a). The upregulation of p53 observed in aged rats contributed to the loss of outer mitochondrial membrane integrity and the mitochondrial-cytochrome c pathway of apoptosis in skeletal muscle (Tamilselvan et al, 2007). Age-related induction of p53-related genes was observed in multiple tissues.…”

Section: Mtdna Content and Mitochondrial Cox Biogenesismentioning

confidence: 99%

Pifithrin-μ increases mitochondrial COX biogenesis and MnSOD activity in skeletal muscle of middle-aged mice

et al. 2012

Mitochondrion

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Age-dependent upregulation of p53 and cytochrome c release and susceptibility to apoptosis in skeletal muscle fiber of aged rats: Role of carnitine and lipoic acid

Cited by 44 publications

References 61 publications

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

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

Isoflurane enhances the expression of cytochrome C by facilitation of NMDA receptor in developing rat hippocampal neurons in vitro

Pifithrin-μ increases mitochondrial COX biogenesis and MnSOD activity in skeletal muscle of middle-aged mice

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