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Christos S. Mantzoros - One of the best experts on this subject based on the ideXlab platform.
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Circulating levels of the components of the GH/IGF-1/IGFBPs axis total and intact IGF-binding proteins (IGFBP) 3 and IGFBP 4 and total IGFBP 5, as well as PAPPA, PAPPA2 and Stanniocalcin-2 levels are not altered in response to Energy Deprivation and/
Metabolism: clinical and experimental, 2019Co-Authors: Eleni Pilitsi, Natia Peradze, Nikolaos Perakakis, Christos S. MantzorosAbstract:Abstract Objective It remains unclear whether food Deprivation induces changes in components of the GH/IGF-1/IGFBPs axis and if yes, which ones are mediated by leptin, an adipocyte secreted hormone regulating neuroendocrine response to Energy Deprivation in animals and humans. We aimed to investigate components of the axis that have not been studied to date, i.e. IGF-binding proteins (IGFBPs) and related proteases (total and intact IGFBP 3 and IGFBP 4, total IGFBP 5, PAPPA, PAPPA2 and Stanniocalcin-2), during acute (short-term fasting in healthy subjects) and chronic (women with hypothalamic amenorrhea [HA] due to excessive exercise) Energy Deprivation and whether metreleptin administration, in replacement, supraphysiologic or pharmacologic levels, may mediate any changes of circulating levels of the above molecules in healthy individuals and in women with hypothalamic amenorrhea. Methods We studied: 1) 11 healthy men and women during three four day admissions i.e. a baseline admission in the fed isocaloric state and two admissions in the complete food Deprivation state for 72-h with either placebo (resulting in a hypoleptinemic state) or metreleptin administration in doses designed to normalize circulating leptin levels for the duration of the study, 2) 15 healthy men and women during three 72-hour long admissions in a complete food Deprivation state receiving three escalating doses of metreleptin designed to bring circulating leptin levels to physiologic, supraphysiologic, or pharmacologic levels, and 3) 18 women with HA randomized to either metreleptin treatment in replacement doses or placebo for nine months. Results There were no significant changes in the circulating profiles of the above molecules in the fasting vs. fed state and/or with metreleptin administration during acute and chronic Energy Deprivation. Conclusions The studied components of the GH/IGF-1/IGFBPs axis are not affected by Energy Deprivation, leptin deficiency associated with Energy Deprivation, or by metreleptin administration in physiologic, supraphysiologic or pharmacologic doses.
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omentin 1 levels are reduced by pharmacologic doses of leptin but remain unaffected by Energy Deprivation and display no day night variation
International Journal of Obesity, 2015Co-Authors: Ole-petter R. Hamnvik, Konstantinos N. Aronis, John P. Chamberland, Bindiya Thakkar, Benjamin E. Schneider, Christos S. MantzorosAbstract:Omentin-1 levels are reduced by pharmacologic doses of leptin, but remain unaffected by Energy Deprivation and display no day–night variation
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Omentin-1 levels are reduced by pharmacologic doses of leptin, but remain unaffected by Energy Deprivation and display no day–night variation
International journal of obesity (2005), 2014Co-Authors: Ole-petter R. Hamnvik, Konstantinos N. Aronis, John P. Chamberland, Bindiya Thakkar, Benjamin E. Schneider, Christos S. MantzorosAbstract:Omentin-1 levels are reduced by pharmacologic doses of leptin, but remain unaffected by Energy Deprivation and display no day–night variation
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chemerin is expressed mainly in pancreas and liver is regulated by Energy Deprivation and lacks day night variation in humans
European Journal of Endocrinology, 2013Co-Authors: John P. Chamberland, Konstantinos N. Aronis, Reena Berman, Christos S. MantzorosAbstract:Objective: Chemerin is an adipocyte-secreted hormone and has recently been associated with obesity and the metabolic syndrome. Although studies in rodents have outlined the aspects of chemerin’s function and expression, its physiology and expression patterns are still to be elucidated in humans. Methods: To evaluate for any day/night variation in chemerin secretion, we analyzed hourly serum samples from six females in the fed state. To examine whether Energy Deprivation affects chemerin levels, and whether this could be mediated through leptin, we analyzed samples from the same subjects in the fasting state while administering either placebo or leptin. To evaluate for any potential dose– effect relationship between leptin and chemerin, we administered increasing metreleptin doses to five females. A tissue array was used to study the expression of chemerin in different human tissues. Ex vivo treatment of human fat explants from three subjects with leptin was carried out to evaluate for any direct effect of leptin on adipocyte chemerin secretion. Results: Chemerin does not display a day/night variation, while acute Energy Deprivation resulted in a significant drop in circulating chemerin levels by w42%. The latter was unaltered by metreleptin administration, and leptin administration did not affect the secretion of chemerin by human adipose tissue studied ex vivo. Chemerin was expressed primarily in the pancreas and liver. Chemerin receptor showed increased expression in the lymph nodes and the spleen. Conclusions: We outline for the first time chemerin expression and physiology in humans, which are different from those in mice.
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Chemerin is expressed mainly in pancreas and liver, is regulated by Energy Deprivation and lacks day/night variation in humans
European journal of endocrinology, 2013Co-Authors: John P. Chamberland, Konstantinos N. Aronis, Reena Berman, Christos S. MantzorosAbstract:Objective: Chemerin is an adipocyte-secreted hormone and has recently been associated with obesity and the metabolic syndrome. Although studies in rodents have outlined the aspects of chemerin’s function and expression, its physiology and expression patterns are still to be elucidated in humans. Methods: To evaluate for any day/night variation in chemerin secretion, we analyzed hourly serum samples from six females in the fed state. To examine whether Energy Deprivation affects chemerin levels, and whether this could be mediated through leptin, we analyzed samples from the same subjects in the fasting state while administering either placebo or leptin. To evaluate for any potential dose– effect relationship between leptin and chemerin, we administered increasing metreleptin doses to five females. A tissue array was used to study the expression of chemerin in different human tissues. Ex vivo treatment of human fat explants from three subjects with leptin was carried out to evaluate for any direct effect of leptin on adipocyte chemerin secretion. Results: Chemerin does not display a day/night variation, while acute Energy Deprivation resulted in a significant drop in circulating chemerin levels by w42%. The latter was unaltered by metreleptin administration, and leptin administration did not affect the secretion of chemerin by human adipose tissue studied ex vivo. Chemerin was expressed primarily in the pancreas and liver. Chemerin receptor showed increased expression in the lymph nodes and the spleen. Conclusions: We outline for the first time chemerin expression and physiology in humans, which are different from those in mice.
Vladimir L. Gabai - One of the best experts on this subject based on the ideXlab platform.
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Regulation of necrosis of H9c2 myogenic cells upon transient Energy Deprivation. Rapid deenergization of mitochondria precedes necrosis and is controlled by reactive oxygen species, stress kinase JNK, HSP72 and ARC.
The Journal of biological chemistry, 2003Co-Authors: Julia A. Yaglom, Vladimir L. Gabai, Daryoush Ekhterae, Michael Y. ShermanAbstract:Abstract Subjecting myogenic H9c2 cells to transient Energy Deprivation leads to a caspase-independent death with typical features of necrosis. Here we show that the rupture of cytoplasmic membrane, the terminal event in necrosis, is shortly preceded by rapid depolarization of mitochondrial membranes. The rapid deenergization of mitochondria critically depended upon prior generation of reactive oxygen species (ROS) during ATP depletion stage. Accordingly, expression of catalase prevented mitochondrial depolarization and averted subsequent necrosis. Interestingly, trifluoperazine, a compound that protects cells from ischemic insults, prevented necrosis of H9c2 cells through inhibition of ROS production. Other factors that regulated the mitochondrial membrane depolarization and subsequent loss of plasma membrane integrity include a stress kinase JNK activated at early steps of recovery from ATP depletion, as well as an apoptotic inhibitory protein ARC. Accordingly, inhibition of JNK or overexpression of ARC prevented mitochondrial depolarization and rescued H9c2 cells from necrosis. ROS and JNK affected mitochondrial deenergization and necrosis independently of each other since inhibition of ROS production did not prevent activation of JNK, whereas inhibition of JNK did not suppress ROS accumulation. Therefore, JNK activation and ROS production represent two independent pathways that control mitochondrial depolarization and subsequent necrosis of cells subjected to transient Energy Deprivation. Overexpression of ARC, although preventing mitochondrial depolarization, did not affect either JNK activation or production of ROS. The major heat shock protein Hsp72 inhibited JNK-related steps of necrotic pathway but did not affect ROS accumulation. Interestingly, mitochondrial depolarization and subsequent necrosis can be suppressed by an Hsp72 mutant Hsp72ΔEEVD, which lacks chaperone function but can efficiently suppress JNK activation. Thus, Hsp72 is directly implicated in a signaling pathway, which leads to necrotic death.
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Suppression of Stress Kinase JNK Is Involved in HSP72-mediated Protection of Myogenic Cells from Transient Energy Deprivation HSP72 ALLEVIATES THE STRESS-INDUCED INHIBITION OF JNK DEPHOSPHORYLATION
The Journal of biological chemistry, 2000Co-Authors: Vladimir L. Gabai, Anatoli B. Meriin, Julia A. Yaglom, Jeanne Y. Wei, Dick D. Mosser, Michael Y. ShermanAbstract:Since protection of cells from stress-induced apoptosis by the heat shock protein Hsp72 involves suppression of stress kinase JNK, we suggested that Hsp72-mediated JNK inhibition might also be critical for myocardial protection from ischemia/reperfusion. Transient Energy Deprivation of H9c2 myogenic cells, used as an in vitro model of myocardial ischemia, led to cell death that had morphological features of apoptosis and necrosis and was independent of caspases. Surprisingly, this unusual type of cell death was regulated by JNK and ERK kinases. In fact, specific inhibition of JNK increased cell survival; specific inhibition of ERKs enhanced deleterious consequences of Energy Deprivation, whereas inhibition of p38 kinase had no effect. Hsp72 suppressed activation of JNK and did not increase ERK activity, suggesting that inhibition of JNK is the important component of Hsp72-mediated protection. Upon transient Energy Deprivation, activation of JNK proceeds via two distinct pathways, stimulation of JNK phosphorylation by a protein kinase SEK1 and inhibition of JNK dephosphorylation. Remarkably, in cells exposed to transient Energy Deprivation, Hsp72 enhanced the rate of JNK dephosphorylation but did not affect SEK1 activity. Therefore, it appears that Hsp72 specifically down-regulates JNK by accelerating its dephosphorylation, which reduces the susceptibility of cardiac cells to simulated ischemia/reperfusion.
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Rise in heat-shock protein level confers tolerance to Energy Deprivation.
FEBS letters, 1993Co-Authors: Vladimir L. Gabai, Alexander E. KabakovAbstract:Abstract Heat shock (44°C for 10 min) or ATP depletion by an uncoupler (CCCP for 20 min) is shown to result in stimulation of hsp68 70 synthesis in Ehrlich tumor cells. After 3 h of recovery, the cells become thermotolerant. Surprisingly, repeated ATP depletion caused by CCCP or rotenone (a respiratory inhibitor) treatment, had a much lower effect on cell viability. Both induction of tolerance to Energy Deprivation and hsp68 70 synthesis were totally suppressed by cycloheximide, an inhibitor of cytosolic protein synthesis. In tolerant cells, rotenone still induced ATP depletion; however, protein aggregation (the rise in Triton-insoluble proteins) was inhibited in these cells. It is suggested that cellular chaperones (e.g. hsp70) are involved in the protection of ischemie cells from necrosis, preventing protein aggregation under ATP deficiency.
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Tumor cell resistance to Energy Deprivation and hyperthermia can be determined by the actin skeleton stability.
Cancer Letters, 1993Co-Authors: Vladimir L. Gabai, Alexander E. KabakovAbstract:Abstract The effect of Energy Deprivation (treatment with rotenone in glucose-free medium) and hyperthermia (44°C) on interphase death of EL-4 thymoma, Ehrlich and HeLa carcinomas was studied in vitro. Irreversible damage accompanied by intensive blebbing with subsequent cell death (necrosis) was observed only when elevation of actin in tritonisoluble fraction occurred although some proteins became insoluble before actin. Actin-specific drugs cytochalasin B and phalloidin accelerated both actin insolubilization and cell necrosis in rotenone-treated EL-4 cells; after conditioning treatment with recovery the actin insolubilization during hyperthermia was suppressed. Ehlrich and HeLa carcinomas were much more resistant to Energy Deprivation and hyperthermia; this correlated with the resistance of their actin to aggregation. It is concluded that stability of actin skeleton may be determinative of tumor cell resistance to Energy Deprivation, hyperthermia and possibly to some other treatments.
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Tumor cell resistance to Energy Deprivation and hyperthermia can be determined by the actin skeleton stability.
Cancer letters, 1993Co-Authors: Vladimir L. Gabai, Alexander E. KabakovAbstract:The effect of Energy Deprivation (treatment with rotenone in glucose-free medium) and hyperthermia (44 degrees C) on interphase death of EL-4 thymoma, Ehrlich and HeLa carcinomas was studied in vitro. Irreversible damage accompanied by intensive blebbing with subsequent cell death (necrosis) was observed only when elevation of actin in triton-insoluble fraction occurred although some proteins became insoluble before actin. Actin-specific drugs cytochalasin B and phalloidin accelerated both actin insolubilization and cell necrosis in rotenone-treated EL-4 cells; after conditioning treatment with recovery the actin insolubilization during hyperthermia was suppressed. Ehlrich and HeLa carcinomas were much more resistant to Energy Deprivation and hyperthermia; this correlated with the resistance of their actin to aggregation. It is concluded that stability of actin skeleton may be determinative of tumor cell resistance to Energy Deprivation, hyperthermia and possibly to some other treatments.
Konstantinos N. Aronis - One of the best experts on this subject based on the ideXlab platform.
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omentin 1 levels are reduced by pharmacologic doses of leptin but remain unaffected by Energy Deprivation and display no day night variation
International Journal of Obesity, 2015Co-Authors: Ole-petter R. Hamnvik, Konstantinos N. Aronis, John P. Chamberland, Bindiya Thakkar, Benjamin E. Schneider, Christos S. MantzorosAbstract:Omentin-1 levels are reduced by pharmacologic doses of leptin, but remain unaffected by Energy Deprivation and display no day–night variation
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Omentin-1 levels are reduced by pharmacologic doses of leptin, but remain unaffected by Energy Deprivation and display no day–night variation
International journal of obesity (2005), 2014Co-Authors: Ole-petter R. Hamnvik, Konstantinos N. Aronis, John P. Chamberland, Bindiya Thakkar, Benjamin E. Schneider, Christos S. MantzorosAbstract:Omentin-1 levels are reduced by pharmacologic doses of leptin, but remain unaffected by Energy Deprivation and display no day–night variation
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gender dimorphism and lack of day night variation or effects of Energy Deprivation on undercarboxylated osteocalcin levels in humans
Obesity, 2013Co-Authors: Joo-pin Foo, Konstantinos N. Aronis, John P. Chamberland, Ole-petter R. Hamnvik, Bindiya Thakkar, Mary BrinkoetterAbstract:Objective Undercarboxylated osteocalcin (ucOC) is a bone marker with potent metabolic effects. Leptin regulates Esp gene expression and osteocalcin carboxylation in animal models. We aim to elucidate day/night patterns of ucOC levels, whether short-term and/or chronic Energy Deprivation alters ucOC levels, and whether leptin may mediate these changes in humans. Design and Methods Twelve healthy males and females were studied for 72 h in the fed state to study day/night pattern of ucOC. The six female subjects were also studied in a crossover interventional study in the fasting state for 72 h with administration of either placebo or metreleptin in physiological doses. Blood samples were obtained hourly from 0800 a.m. on day 3 until 0800 a.m. on day 4. In a separate study, eleven obese subjects who underwent bariatric surgery were followed for 24 weeks to examine the effects of postsurgery weight loss on ucOC levels. Results Males have higher ucOC levels compared to females. There is no day/night variation pattern of circulating ucOC in humans. Short-term and chronic Energy Deprivation or leptin administrations do not alter ucOC levels. Conclusions The hypothesis that ucOC plays a role in Energy homeostasis or of leptin in regulating ucOC in humans is not supported.
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chemerin is expressed mainly in pancreas and liver is regulated by Energy Deprivation and lacks day night variation in humans
European Journal of Endocrinology, 2013Co-Authors: John P. Chamberland, Konstantinos N. Aronis, Reena Berman, Christos S. MantzorosAbstract:Objective: Chemerin is an adipocyte-secreted hormone and has recently been associated with obesity and the metabolic syndrome. Although studies in rodents have outlined the aspects of chemerin’s function and expression, its physiology and expression patterns are still to be elucidated in humans. Methods: To evaluate for any day/night variation in chemerin secretion, we analyzed hourly serum samples from six females in the fed state. To examine whether Energy Deprivation affects chemerin levels, and whether this could be mediated through leptin, we analyzed samples from the same subjects in the fasting state while administering either placebo or leptin. To evaluate for any potential dose– effect relationship between leptin and chemerin, we administered increasing metreleptin doses to five females. A tissue array was used to study the expression of chemerin in different human tissues. Ex vivo treatment of human fat explants from three subjects with leptin was carried out to evaluate for any direct effect of leptin on adipocyte chemerin secretion. Results: Chemerin does not display a day/night variation, while acute Energy Deprivation resulted in a significant drop in circulating chemerin levels by w42%. The latter was unaltered by metreleptin administration, and leptin administration did not affect the secretion of chemerin by human adipose tissue studied ex vivo. Chemerin was expressed primarily in the pancreas and liver. Chemerin receptor showed increased expression in the lymph nodes and the spleen. Conclusions: We outline for the first time chemerin expression and physiology in humans, which are different from those in mice.
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Chemerin is expressed mainly in pancreas and liver, is regulated by Energy Deprivation and lacks day/night variation in humans
European journal of endocrinology, 2013Co-Authors: John P. Chamberland, Konstantinos N. Aronis, Reena Berman, Christos S. MantzorosAbstract:Objective: Chemerin is an adipocyte-secreted hormone and has recently been associated with obesity and the metabolic syndrome. Although studies in rodents have outlined the aspects of chemerin’s function and expression, its physiology and expression patterns are still to be elucidated in humans. Methods: To evaluate for any day/night variation in chemerin secretion, we analyzed hourly serum samples from six females in the fed state. To examine whether Energy Deprivation affects chemerin levels, and whether this could be mediated through leptin, we analyzed samples from the same subjects in the fasting state while administering either placebo or leptin. To evaluate for any potential dose– effect relationship between leptin and chemerin, we administered increasing metreleptin doses to five females. A tissue array was used to study the expression of chemerin in different human tissues. Ex vivo treatment of human fat explants from three subjects with leptin was carried out to evaluate for any direct effect of leptin on adipocyte chemerin secretion. Results: Chemerin does not display a day/night variation, while acute Energy Deprivation resulted in a significant drop in circulating chemerin levels by w42%. The latter was unaltered by metreleptin administration, and leptin administration did not affect the secretion of chemerin by human adipose tissue studied ex vivo. Chemerin was expressed primarily in the pancreas and liver. Chemerin receptor showed increased expression in the lymph nodes and the spleen. Conclusions: We outline for the first time chemerin expression and physiology in humans, which are different from those in mice.
John P. Chamberland - One of the best experts on this subject based on the ideXlab platform.
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omentin 1 levels are reduced by pharmacologic doses of leptin but remain unaffected by Energy Deprivation and display no day night variation
International Journal of Obesity, 2015Co-Authors: Ole-petter R. Hamnvik, Konstantinos N. Aronis, John P. Chamberland, Bindiya Thakkar, Benjamin E. Schneider, Christos S. MantzorosAbstract:Omentin-1 levels are reduced by pharmacologic doses of leptin, but remain unaffected by Energy Deprivation and display no day–night variation
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Omentin-1 levels are reduced by pharmacologic doses of leptin, but remain unaffected by Energy Deprivation and display no day–night variation
International journal of obesity (2005), 2014Co-Authors: Ole-petter R. Hamnvik, Konstantinos N. Aronis, John P. Chamberland, Bindiya Thakkar, Benjamin E. Schneider, Christos S. MantzorosAbstract:Omentin-1 levels are reduced by pharmacologic doses of leptin, but remain unaffected by Energy Deprivation and display no day–night variation
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gender dimorphism and lack of day night variation or effects of Energy Deprivation on undercarboxylated osteocalcin levels in humans
Obesity, 2013Co-Authors: Joo-pin Foo, Konstantinos N. Aronis, John P. Chamberland, Ole-petter R. Hamnvik, Bindiya Thakkar, Mary BrinkoetterAbstract:Objective Undercarboxylated osteocalcin (ucOC) is a bone marker with potent metabolic effects. Leptin regulates Esp gene expression and osteocalcin carboxylation in animal models. We aim to elucidate day/night patterns of ucOC levels, whether short-term and/or chronic Energy Deprivation alters ucOC levels, and whether leptin may mediate these changes in humans. Design and Methods Twelve healthy males and females were studied for 72 h in the fed state to study day/night pattern of ucOC. The six female subjects were also studied in a crossover interventional study in the fasting state for 72 h with administration of either placebo or metreleptin in physiological doses. Blood samples were obtained hourly from 0800 a.m. on day 3 until 0800 a.m. on day 4. In a separate study, eleven obese subjects who underwent bariatric surgery were followed for 24 weeks to examine the effects of postsurgery weight loss on ucOC levels. Results Males have higher ucOC levels compared to females. There is no day/night variation pattern of circulating ucOC in humans. Short-term and chronic Energy Deprivation or leptin administrations do not alter ucOC levels. Conclusions The hypothesis that ucOC plays a role in Energy homeostasis or of leptin in regulating ucOC in humans is not supported.
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chemerin is expressed mainly in pancreas and liver is regulated by Energy Deprivation and lacks day night variation in humans
European Journal of Endocrinology, 2013Co-Authors: John P. Chamberland, Konstantinos N. Aronis, Reena Berman, Christos S. MantzorosAbstract:Objective: Chemerin is an adipocyte-secreted hormone and has recently been associated with obesity and the metabolic syndrome. Although studies in rodents have outlined the aspects of chemerin’s function and expression, its physiology and expression patterns are still to be elucidated in humans. Methods: To evaluate for any day/night variation in chemerin secretion, we analyzed hourly serum samples from six females in the fed state. To examine whether Energy Deprivation affects chemerin levels, and whether this could be mediated through leptin, we analyzed samples from the same subjects in the fasting state while administering either placebo or leptin. To evaluate for any potential dose– effect relationship between leptin and chemerin, we administered increasing metreleptin doses to five females. A tissue array was used to study the expression of chemerin in different human tissues. Ex vivo treatment of human fat explants from three subjects with leptin was carried out to evaluate for any direct effect of leptin on adipocyte chemerin secretion. Results: Chemerin does not display a day/night variation, while acute Energy Deprivation resulted in a significant drop in circulating chemerin levels by w42%. The latter was unaltered by metreleptin administration, and leptin administration did not affect the secretion of chemerin by human adipose tissue studied ex vivo. Chemerin was expressed primarily in the pancreas and liver. Chemerin receptor showed increased expression in the lymph nodes and the spleen. Conclusions: We outline for the first time chemerin expression and physiology in humans, which are different from those in mice.
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Chemerin is expressed mainly in pancreas and liver, is regulated by Energy Deprivation and lacks day/night variation in humans
European journal of endocrinology, 2013Co-Authors: John P. Chamberland, Konstantinos N. Aronis, Reena Berman, Christos S. MantzorosAbstract:Objective: Chemerin is an adipocyte-secreted hormone and has recently been associated with obesity and the metabolic syndrome. Although studies in rodents have outlined the aspects of chemerin’s function and expression, its physiology and expression patterns are still to be elucidated in humans. Methods: To evaluate for any day/night variation in chemerin secretion, we analyzed hourly serum samples from six females in the fed state. To examine whether Energy Deprivation affects chemerin levels, and whether this could be mediated through leptin, we analyzed samples from the same subjects in the fasting state while administering either placebo or leptin. To evaluate for any potential dose– effect relationship between leptin and chemerin, we administered increasing metreleptin doses to five females. A tissue array was used to study the expression of chemerin in different human tissues. Ex vivo treatment of human fat explants from three subjects with leptin was carried out to evaluate for any direct effect of leptin on adipocyte chemerin secretion. Results: Chemerin does not display a day/night variation, while acute Energy Deprivation resulted in a significant drop in circulating chemerin levels by w42%. The latter was unaltered by metreleptin administration, and leptin administration did not affect the secretion of chemerin by human adipose tissue studied ex vivo. Chemerin was expressed primarily in the pancreas and liver. Chemerin receptor showed increased expression in the lymph nodes and the spleen. Conclusions: We outline for the first time chemerin expression and physiology in humans, which are different from those in mice.
Alexander E. Kabakov - One of the best experts on this subject based on the ideXlab platform.
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Rise in heat-shock protein level confers tolerance to Energy Deprivation.
FEBS letters, 1993Co-Authors: Vladimir L. Gabai, Alexander E. KabakovAbstract:Abstract Heat shock (44°C for 10 min) or ATP depletion by an uncoupler (CCCP for 20 min) is shown to result in stimulation of hsp68 70 synthesis in Ehrlich tumor cells. After 3 h of recovery, the cells become thermotolerant. Surprisingly, repeated ATP depletion caused by CCCP or rotenone (a respiratory inhibitor) treatment, had a much lower effect on cell viability. Both induction of tolerance to Energy Deprivation and hsp68 70 synthesis were totally suppressed by cycloheximide, an inhibitor of cytosolic protein synthesis. In tolerant cells, rotenone still induced ATP depletion; however, protein aggregation (the rise in Triton-insoluble proteins) was inhibited in these cells. It is suggested that cellular chaperones (e.g. hsp70) are involved in the protection of ischemie cells from necrosis, preventing protein aggregation under ATP deficiency.
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Tumor cell resistance to Energy Deprivation and hyperthermia can be determined by the actin skeleton stability.
Cancer Letters, 1993Co-Authors: Vladimir L. Gabai, Alexander E. KabakovAbstract:Abstract The effect of Energy Deprivation (treatment with rotenone in glucose-free medium) and hyperthermia (44°C) on interphase death of EL-4 thymoma, Ehrlich and HeLa carcinomas was studied in vitro. Irreversible damage accompanied by intensive blebbing with subsequent cell death (necrosis) was observed only when elevation of actin in tritonisoluble fraction occurred although some proteins became insoluble before actin. Actin-specific drugs cytochalasin B and phalloidin accelerated both actin insolubilization and cell necrosis in rotenone-treated EL-4 cells; after conditioning treatment with recovery the actin insolubilization during hyperthermia was suppressed. Ehlrich and HeLa carcinomas were much more resistant to Energy Deprivation and hyperthermia; this correlated with the resistance of their actin to aggregation. It is concluded that stability of actin skeleton may be determinative of tumor cell resistance to Energy Deprivation, hyperthermia and possibly to some other treatments.
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Tumor cell resistance to Energy Deprivation and hyperthermia can be determined by the actin skeleton stability.
Cancer letters, 1993Co-Authors: Vladimir L. Gabai, Alexander E. KabakovAbstract:The effect of Energy Deprivation (treatment with rotenone in glucose-free medium) and hyperthermia (44 degrees C) on interphase death of EL-4 thymoma, Ehrlich and HeLa carcinomas was studied in vitro. Irreversible damage accompanied by intensive blebbing with subsequent cell death (necrosis) was observed only when elevation of actin in triton-insoluble fraction occurred although some proteins became insoluble before actin. Actin-specific drugs cytochalasin B and phalloidin accelerated both actin insolubilization and cell necrosis in rotenone-treated EL-4 cells; after conditioning treatment with recovery the actin insolubilization during hyperthermia was suppressed. Ehlrich and HeLa carcinomas were much more resistant to Energy Deprivation and hyperthermia; this correlated with the resistance of their actin to aggregation. It is concluded that stability of actin skeleton may be determinative of tumor cell resistance to Energy Deprivation, hyperthermia and possibly to some other treatments.