Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.61 (caspase-8)
 6,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The long-lived growth hormone (GH) receptor knockout (GHRKO; KO) mice are GH-resistant due to targeted disruption of the GH receptor (Ghr) gene. Apoptosis is a physiological process in which cells play an active role in their own death and is a normal component of the development and health of multicellular organisms. Aging is associated with the progressive loss of strength of skeletal and heart muscles. Calorie restriction (CR) is a well-known experimental model to delay aging and increase lifespan. The aim of the study was to examine the expression of the following apoptosis-related genes: caspase-3, caspase-9, caspase-8, bax, bcl-2, Smac/DIABLO, p53 and cytochrome c1 (cyc1) in the skeletal muscles and hearts of female normal and GHRKO mice, fed ad libitum or subjected to 40% CR for six months, starting at two months of age. Moreover, skeletal muscle caspase-3, caspase-9, caspase-8, bax, bcl-2, Smac/DIABLO, Apaf-1, bad, phospho-bad (pbad), phospho-p53 and cytochrome c (cyc) protein expression levels were assessed. Expression of caspase-3, caspase-9, bax and Smac/DIABLO genes and proteins was decreased in GHRKO's skeletal muscles. The Apaf-1 protein expression also was diminished in this tissue. In contrast, bcl-2 and pbad protein levels were increased in skeletal muscles in knockouts. No changes were demonstrated for the examined genes' expression in GHRKO's hearts except for the increased level of cyc1 mRNA. CR did not alter the expression of the examined genes and proteins in skeletal muscles of knockouts versus normal (N) mice. In heart homogenates, CR increased caspase-3 mRNA level as compared with ad libitum mice. Decreased expression of certain proapoptotic genes and/or proteins may constitute the potential mechanism of prolonged longevity in GHRKO mice, protecting these animals from aging; this potential beneficial mechanism is not affected by CR.
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PMID:Decreased expression level of apoptosis-related genes and/or proteins in skeletal muscles, but not in hearts, of growth hormone receptor knockout mice. 2132 12

Growth hormone (GH) receptor knockout (GHRKO) mice are highly insulin sensitive and long-lived. Surgical visceral fat removal (VFR) improves insulin signaling in normal mice and rats and extends longevity in rats. We have previously demonstrated decreased expression of certain pro-apoptotic genes in kidneys of GHRKO mice and suggested that this could contribute to the increased longevity of these animals. The aim of the present study was to examine the level of the following proteins: caspase-3, caspase-9, caspase-8, bax, bad, phospho-bad, bcl-2, Smac/DIABLO, Apaf-1, phospho-p53 (pp53) and cytochrome c in male GHRKO and normal (N) mice subjected to VFR or sham surgery, at approximately six months of age. The kidneys were collected two months after VFR. Caspase-3, caspase-8, bax, bad, Smac/DIABLO, Apaf-1 and pp53 levels were decreased in GHRKO mice as compared to N animals. VFR did not change the level of any of the examined proteins. The decreased renal levels of pro-apoptotic proteins could contribute to the extended life-span caused by targeted disruption of the GH receptor gene but are apparently not involved in mediating the effects of VFR.
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PMID:Renal pro-apoptotic proteins are reduced by growth hormone resistance but not by visceral fat removal. 2139 71

Mice homozygous for the targeted disruption of the growth hormone (GH) receptor (Ghr) gene (GH receptor knockout; GHRKO; KO) are hypoinsulinemic, highly insulin sensitive, normoglycemic, and long-lived. Visceral fat removal (VFR) is a surgical intervention which improves insulin signaling in normal (N) mice and rats and extends longevity in rats. We have previously demonstrated decreased expression level of certain pro-apoptotic genes in skeletal muscles and suggested that this may contribute to the regulation of longevity in GHRKO mice. Alterations in apoptosis-related genes expression in the kidneys also may potentially lead to lifespan extension. In this context, we decided to examine the renal expression of the following genes: caspase-3, caspase-9, caspase-8, bax, bad, bcl-2, Smac/DIABLO, Apaf-1, p53, and cytochrome c1 (cyc1) in male GHRKO and N mice subjected to VFR or sham surgery, at approximately 6 months of age. The kidneys were collected 2 months after VFR. As a result, caspase-3, caspase-9, and bax expressions were decreased in KO mice as compared to N animals. Expressions of Smac/DIABLO, caspase-8, bcl-2, bad, and p53 did not differ between KOs and N mice. VFR did not change the expression of the examined genes in KO or N mice. In conclusion, endocrine abnormalities in GHRKO mice result in decreased expression of pro-apoptotic genes and VFR did not alter the examined genes expression in N and KO mice. These data are consistent with a model in which alterations of GH signaling and/or insulin sensitivity lead to increased lifespan mediated by decreased renal expression of pro-apoptotic genes.
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PMID:Deletion of growth hormone receptor gene but not visceral fat removal decreases expression of apoptosis-related genes in the kidney-potential mechanism of lifespan extension. 2143 51