Elevated sphingomyelinase activity and ceramide concentration in serum of patients undergoing high dose spatially fractionated radiation treatment: Implications for endothelial apoptosis

Sathishkumar, S.; Boyanovsky, Boris B.; Karakashian, Alexander A.; Rozenova, Krassimira A.; Giltiay, Natalia V.; Kudrimoti, Mahesh; Mohiuddin, Mohammed; Ahmed, Mansoor M.; Nikolova‐Karakashian, Mariana

doi:10.4161/cbt.4.9.1915

Cited by 113 publications

(97 citation statements)

References 47 publications

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“…The regions migrating with the standard ceramide were scraped from the plate and ceramide eluted from the silica with 1 ml chloroform/methanol (1:1, v/v) followed by 1 ml of methanol. The combined eluates were dried in vacuo, and ceramide mass was quantified by long-chain bases released after an acid hydrolysis in 0.5 M HCl in methanol at 65°C for 15 h (Sathishkumar et al 2005). Free long-chain bases were analyzed as described by Lauter and Trams (1962).…”

Section: Extraction and Separation Of Lipidsmentioning

confidence: 99%

Vitamin E prevents the age-dependent and palmitate-induced disturbances of sphingolipid turnover in liver cells

Babenko

Hassouneh

Kharchenko

et al. 2011

AGE

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Sphingolipid turnover has been shown to be activated at old age and in response to various stress stimuli including oxidative stress. Reduction of vitamin E content in the liver under the pro-oxidant action is associated with enhanced sphingolipid turnover and ceramide accumulation in hepatocytes. In the present paper, the correction of sphingolipid metabolism in the liver cells of old rats and in the palmitate-treated young hepatocytes using α-tocopherol has been investigated. 3-and 24-month-old rats, [ 14 C] palmitic acid, [methyl− 14 C-choline]sphingomyelin (SM), and [ 14 C]serine were used. α-Tocopherol administration to old rats or addition to the culture medium of old liver slices or hepatocytes prevented age-dependent increase of ceramide synthesis and lipid accumulation, and increased SM content in liver tissue and cells. α-Tocopherol treatment of old cells decreased the neutral and acid sphingomyelinase (SMase) activities in hepatocytes and serine palmitoyl transferase activity in the liver cell microsomes. Effect of α-or γ-tocopherol, but not of δ-tocopherol, on the newly synthesized ceramide content in old cells was correlated with the action of inhibitor of serine palmitoyl transferase (SPT) activity (myriocin) and SMase inhibitors (glutathione, imipramine). Addition of α-tocopherol as well as myriocin to the culture medium of young hepatocytes, treated by palmitate, abolished ceramide accumulation and synthesis. The data obtained demonstrate that α-tocopherol normalized elevated ceramide content in the old liver cells via inhibition of acid and neutral SMase activities and lipid synthesis de novo. α-Tocopherol, reducing ceramide synthesis, prevented palmitate-induced aging-like ceramide accumulation in young liver cells.

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Section: Extraction and Separation Of Lipidsmentioning

confidence: 99%

Vitamin E prevents the age-dependent and palmitate-induced disturbances of sphingolipid turnover in liver cells

Babenko

Hassouneh

Kharchenko

et al. 2011

AGE

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“…In addition, as the endothelium is known to be a rich source of S-ASM, diseases with endothelial involvement actually appear to present a marked elevation in peripheral S-ASM activity. Mild elevations of blood S-ASM activity were observed in Alzheimer's disease (Lee et al 2014), type 2 diabetes mellitus (Górska et al 2003), stable angina pectoris (Pan et al 2014), acute myocardial infarction (Pan et al 2014), chronic heart failure (Doehner et al 2007), post-traumatic stress disorder (Hammad et al 2012), and in response to ionizing radiation treatment in cancer patients (Sathishkumar et al 2005). Marked elevations of blood S-ASM activity were observed in unstable angina pectoris (Pan et al 2014), Wilson disease (Lang et al 2007), sepsis (Claus et al 2005), systemic inflammatory response syndrome (Kott et al 2014), lymphohistiocytosis (Takahashi et al 2002;Jenkins et al 2013), non-alcoholic fatty liver (Grammatikos et al 2014), hepatitis C (Grammatikos et al 2014), systemic vasculitis inflammatory renal disease (Kiprianos et al 2012), and in patients with alcohol dependency undergoing withdrawal .…”

Section: +mentioning

confidence: 99%

Elevation of Serum Acid Sphingomyelinase Activity in Children with Acute Respiratory Syncytial Virus Bronchiolitis

Yoshida

Noguchi

Kikuchi³

et al. 2017

Tohoku J. Exp. Med.

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Acid sphingomyelinase (ASM) is a lysosomal enzyme that hydrolyzes sphingomyelin into ceramide, a bioactive lipid to regulate cellular physiological functions. Thus, ASM activation has been reported as a key event in pathophysiological reactions including inflammation, cytokine release, oxidative stress, and endothelial damage in human diseases. Since ASM activation is associated with extracellular ASM secretion through unknown mechanisms, it can be detected by recognizing the elevation of secretory ASM (S-ASM) activity. Serum S-ASM activity has been reported to increase in chronic diseases, acute cardiac diseases, and systemic inflammatory diseases. However, the serum S-ASM has not been investigated in common acute illness. This study was designed to evaluate serum S-ASM activity in children with common acute illness. Fifty children with common acute illness and five healthy children were included in this study. The patients were categorized into five groups based on clinical diagnoses: acute respiratory syncytial virus (RSV) bronchiolitis, adenovirus infection, streptococcal infection, asthma, and other infections due to unknown origin. The serum S-ASM activity was significantly elevated at 6.9 ± 1.6 nmol/0.1 mL/6 h in the group of acute RSV bronchiolitis patients compared with healthy children who had a mean level of 1.8 ± 0.8 nmol/0.1 mL/6 h (p < 0.05). In the other illness groups, the serum S-ASM activity was not significantly elevated. The results suggest an association of ASM activation with RSV infection, a cause for common acute illness. This is the first report to describe the elevation of serum S-ASM activity in respiratory tract infection.

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“…Studies of the abscopal effect also focus upon pivotal roles of increased ceramide levels, leading to apoptotic signaling [14,48]. The absorbed dose of 20 Gy applied in the present study is comparable to the absorbed dose of 15 Gy which has been used to raise ceramide levels in circulation that might induce apoptotic death of cancer cells also in nonirradiated areas [49]. Numerous reports have revealed that activation of secretoric acid sphingomyelinase (sSMase) by chemotherapeutic agents resulted raising intracellular ceramide levels and increased death of cancer cells [50,51].…”

Section: Mechanisms Of the Abscopal Effectmentioning

confidence: 60%

“Abscopal” Effect of Radiation Therapy Combined with Immune-Therapy Using IFN-γ Gene Transfected Syngeneic Tumor Cells, in Rats with Bilateral Implanted N29 Tumors

et al. 2011

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The tumor growth rate response was studied on N29 rat glioma tumor cells subcutaneously implanted on both hind legs of Fischer-344 rats. At around 30 days after inoculation, RT was given with 60 Co gamma radiation with 4 daily fractions of 5 Gy only to the right-lateral tumors. At days 26, 42, and 54 after inoculation, immunization was performed with irradiated syngeneic IFNγ-gene transfected cells. Tumor growth rate (TGR % per day) of the right-lateral irradiated tumor was significantly decreased (P < 0.01) after RT alone and with the combination of RT and immunization. But immunization alone gave no significant decrease of the TGR but significantly increased time of survival. The TGR of the unirradiated left-lateral tumors was significantly decreased (P < 0.02) only in the group of rats treated with RT alone. It is apparent that tumor cells killed by the radiation mediate suppression of tumor cells outside the target area. This effect is called the abscopal effect.

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Elevated sphingomyelinase activity and ceramide concentration in serum of patients undergoing high dose spatially fractionated radiation treatment: Implications for endothelial apoptosis

Cited by 113 publications

References 47 publications

Vitamin E prevents the age-dependent and palmitate-induced disturbances of sphingolipid turnover in liver cells

Vitamin E prevents the age-dependent and palmitate-induced disturbances of sphingolipid turnover in liver cells

Elevation of Serum Acid Sphingomyelinase Activity in Children with Acute Respiratory Syncytial Virus Bronchiolitis

“Abscopal” Effect of Radiation Therapy Combined with Immune-Therapy Using IFN-γ Gene Transfected Syngeneic Tumor Cells, in Rats with Bilateral Implanted N29 Tumors

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