Caenorhabditis elegansContains Two Distinct Acid Sphingomyelinases

Lin, Xinhua; Hengartner, Michael O.; Kolesnick, Richard

doi:10.1074/jbc.273.23.14374

Cited by 35 publications

(26 citation statements)

References 30 publications

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“…These proteins contain six conserved cysteines that potentially form three disulfide bridges, as observed in members of the amoebapore superfamily (Zhai & Saier 2000). This superfamily includes amoebapores (Ravdin 1989), saposins (O'Brien & Kishimoto 1991), NK-lysins (Andersson et al 1995), granulysins (Pena et al 1997), pulmonary surfactant-associated proteins (Hawgood et al 1987), acid sphingomyelinases (Lin et al 1998), acyloxyacyl hydrolases (Staab et al 1994) and aspartic proteases (Kervinen et al 1999). The disulfide bridges in all amoebapore superfamily members render these proteins remarkably stable to heat, acid and other conditions.…”

Section: Discussionmentioning

confidence: 99%

Two cell‐counting factors regulate the aggregate size of the cellular slime mold Dictyostelium discoideum

Okuwa¹,

Katayama²,

Takano³

et al. 2001

Dev Growth Differ

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Countin, a cell-counting factor in Dictyostelium discoideum, is considered to limit the maximum size of the multicellular structure, because a countin null strain forms a huge fruiting body compared to that of the wildtype. A novel gene, countin2, that is highly homologous to countin (40% identity in amino acid sequence) was identified in the D. discoideum genome. The countin2 null strain formed a 1.7-fold higher number of the aggregates, resulting in smaller fruiting bodies compared with those of wild-type cells. Thus, the Countin2 protein is thought to limit the minimum size of the multicellular structure. The size and number of aggregates formed by a mixture of countin null and countin2 null strains were the same as those of the wild-type. These findings demonstrate that a combination of Countin and Countin2 proteins determines the appropriate size of the multicellular structure of D. discoideum.

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Section: Discussionmentioning

confidence: 99%

Two cell‐counting factors regulate the aggregate size of the cellular slime mold Dictyostelium discoideum

Okuwa¹,

Katayama²,

Takano³

et al. 2001

Dev Growth Differ

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“…By contrast, in the nematode Caenorhabditis elegans, three genes have been identified (Lin et al, 1998;Kim and Sun, 2012) on different chromosomes (Yook et al, 2012): the product of asm-1 is almost entirely secreted but is Zn 2+ -independent, whereas only 20% of the asm-2 product is secreted and requires Zn 2+ . The asm-3 protein with the strongest homology to human ASM and sensitivity to desipramine and clomipramine (Lin et al, 1998;Kim and Sun, 2012) may correspond to L-ASM. The presence of separate genes for the secreted sphingomyelinase in C. elegans with developmentally regulated expression emphasizes the critical importance of the secreted enzyme.…”

Section: Introductionmentioning

confidence: 99%

“…The common mRNA is also translated in the same reading frame because the resulting L-and S-ASM proteins are similar in size and are both recognized by antibodies prepared against L-ASM (Schissel et al, 1996a(Schissel et al, , 1998b. By contrast, in the nematode Caenorhabditis elegans, three genes have been identified (Lin et al, 1998;Kim and Sun, 2012) on different chromosomes (Yook et al, 2012): the product of asm-1 is almost entirely secreted but is Zn 2+ -independent, whereas only 20% of the asm-2 product is secreted and requires Zn 2+ . The asm-3 protein with the strongest homology to human ASM and sensitivity to desipramine and clomipramine (Lin et al, 1998;Kim and Sun, 2012) may correspond to L-ASM.…”

Section: Introductionmentioning

confidence: 99%

Secretory sphingomyelinase in health and disease

Kornhuber

Rhein

Müller

et al. 2015

Biological Chemistry

122

138

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Acid sphingomyelinase (ASM), a key enzyme in sphingolipid metabolism, hydrolyzes sphingomyelin to ceramide and phosphorylcholine. In mammals, the expression of a single gene, SMPD1, results in two forms of the enzyme that differ in several characteristics. Lysosomal ASM (L-ASM) is located within the lysosome, requires no additional Zn 2+ ions for activation and is glycosylated mainly with high-mannose oligosaccharides. By contrast, the secretory ASM (S-ASM) is located extracellularly, requires Zn 2+ ions for activation, has a complex glycosylation pattern and has a longer in vivo half-life. In this review, we summarize current knowledge regarding the physiology and pathophysiology of S-ASM, including its sources and distribution, molecular and cellular mechanisms of generation and regulation and relevant in vitro and in vivo studies. Polymorphisms or mutations of SMPD1 lead to decreased S-ASM activity, as detected in patients with Niemann-Pick disease B. Thus, lower serum/ plasma activities of S-ASM are trait markers. No genetic causes of increased S-ASM activity have been identified. Instead, elevated activity is the result of enhanced release (e.g., induced by lipopolysaccharide and cytokine stimulation) or increased enzyme activation (e.g., induced by oxidative stress). Increased S-ASM activity in serum or plasma is a state marker of a wide range of diseases. In particular, high S-ASM activity occurs in inflammation of the endothelium and liver. Several studies have demonstrated a correlation between S-ASM activity and mortality induced by severe inflammatory diseases. Serial measurements of S-ASM reveal prolonged activation and, therefore, the measurement of this enzyme may also provide information on past inflammatory processes. Thus, S-ASM may be both a promising clinical chemistry marker and a therapeutic target.

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“…a ASMase and NSMase activities were measured as in (84). Sphingomyelin levels were determined by charring as described in (85).…”

Section: Characterization Of Asmasementioning

confidence: 99%

Natural Ceramide Reverses Fas Resistance of Acid Sphingomyelinase −− Hepatocytes

Pâris¹,

Grassmé

Cremesti³

et al. 2001

Journal of Biological Chemistry

Self Cite

116

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The role of the second messenger ceramide in Fasmediated death requires clarification. To address this issue, we generated hepatocytes from paired acid sphingomyelinase (ASMase; asmase) ؉/؉ and asmase ؊/؊ mice. asmase ؊/؊ hepatocytes, derived from 8-week-old mice, manifested normal sphingomyelin content and normal morphological, biochemical, and biologic features. Nonetheless, ASMase-deficient hepatocytes did not display rapid ceramide elevation or apoptosis in response to Jo2 anti-Fas antibody. asmase ؊/؊ hepatocytes were not inherently resistant to apoptosis because staurosporine, which did not induce early ceramide elevation, stimulated a normal apoptotic response. The addition of low nanomolar quantities of natural C 16 -ceramide, which by itself did not induce apoptosis, completely restored the apoptotic response to anti-Fas in asmase ؊/؊ hepatocytes. Other sphingolipids did not replace natural ceramide and restore Fas sensitivity. Overcoming resistance to Fas in asmase ؊/؊ hepatocytes by natural ceramide is evidence that it is the lack of ceramide and not ASMase which determines the apoptotic phenotype. The ability of natural ceramide to rescue the phenotype without reversing the genotype provides evidence that ceramide is obligate for Fas induction of apoptosis in hepatocytes.

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Caenorhabditis elegansContains Two Distinct Acid Sphingomyelinases

Cited by 35 publications

References 30 publications

Two cell‐counting factors regulate the aggregate size of the cellular slime mold Dictyostelium discoideum

Two cell‐counting factors regulate the aggregate size of the cellular slime mold Dictyostelium discoideum

Secretory sphingomyelinase in health and disease

Natural Ceramide Reverses Fas Resistance of Acid Sphingomyelinase −− Hepatocytes

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