Disease relevance of SLN

• In pressure overload, targeted increases in D2 activity could not block hypertrophy but could completely prevent impaired contractility and SR Ca(2+) cycling as well as altered expression patterns of SERCA2a, SLN, and other markers of pathological hypertrophy [1].
• This review focuses on advances in the understanding of molecular regulation of SERCA2a by PLN and SLN, and their implications for cardiac hypertrophy and failure in vivo [2].
• Briefly, recombinant wild-type PLB and SLN were over-produced in Escherichia coli as maltose binding protein fusion proteins [3].
• Down-regulation of sarcolipin mRNA expression in chronic atrial fibrillation [4].
• The use of reverse transcription-PCR analysis to increase detection of tumor cells in SLN of breast cancer patients is hampered by the lack of specific markers [5].

Psychiatry related information on SLN

• If SLN positive patients decline the standard recommendation of CAD or entry into clinical trials evaluating the significance of CAD then the BCN could help in decision making [6].

High impact information on SLN

• These phenotypic changes were associated with up-regulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) 2a expression as well as decreased Na(+)/Ca(2+) exchanger, beta-myosin heavy chain, and sarcolipin (SLN) expression [1].
• These homologous proteins differ at their N and C termini: the C-terminal Met-Leu-Leu in PLN is replaced by Arg-Ser-Tyr-Gln-Tyr in SLN [7].
• Modeling showed that the SLN/SERCA1a complex closely resembles the PLN/SERCA1a complex, but with the luminal end of SLN extending to the loop connecting M1 and M2, where Tyr-29 and Tyr-31 interact with aromatic residues in SERCA1a [8].
• The Ca(2+)-ATPase is implicated in thermogenesis in some types of muscle; this could involve processes of slippage and leak modulated by interaction between the Ca(2+)-ATPase and sarcolipin [9].
• There was a major up-regulation of proteins interacting with calcium, namely S100 calcium-binding proteins and sarcolipin, a sarcoplasmic calcium regulator [10].

Chemical compound and disease context of SLN

• Regulation of sarco(endo)plasmic reticulum Ca2+ adenosine triphosphatase by phospholamban and sarcolipin: implication for cardiac hypertrophy and failure [2].
• According to recent standards detection of the SLN should be performed by a triple approach: injection of 90 nm Technetium and patent blue in the periphery of the primary melanoma, and intraoperative tracing of radioactivity with the aid of a hand-held gamma probe [11].

Biological context of SLN

• SLN and PLN genes resemble each other in having two small exons, with their entire coding sequences lying in exon 2 and a large intron separating the two segments [12].
• Genomic DNA and cDNA encoding human sarcolipin (SLN) were isolated and characterized and the SLN gene was mapped to chromosome 11q22-q23 [12].
• Sarcolipin (SLN), a 31 amino acid integral membrane protein, regulates SERCA1a and SERCA2a, two isoforms of the sarco(endo)plasmic Ca-ATPase, by lowering their apparent Ca(2+) affinity and thereby enabling muscle relaxation [13].
• NF-SLN cDNA (SLN tagged N-terminally with a FLAG epitope) was introduced into rat soleus muscle in one hindlimb by plasmid injection and electrotransfer [14].
• Even at a 50:1 molar ratio of SLN/ATPase, SLN had no significant effect on the rate of ATP hydrolysis by the ATPase or on the Ca(2+)-dependence of ATP hydrolysis [15].

Anatomical context of SLN

• The 31-amino acid proteolipid, sarcolipin (SLN), is associated with the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+-ATPase (SERCA1) [16].
• Immunohistochemistry was used to demonstrate colocalization of NF-SLN and SERCA1 in the endoplasmic reticulum membrane and to demonstrate the cytosolic orientation of the N terminus of SLN [16].
• Like SERCA1, SLN is highly expressed in rabbit fast-twitch skeletal muscle, but it is expressed to a lower extent in slow-twitch muscle and to an even lower extent in cardiac muscle, where SERCA2a and PLN are highly expressed [12].
• SLN is expressed in both fast-twitch and slow-twitch muscle fibers with significant expression levels also found in the cardiac muscle [13].
• Sarcolipin inhibits polymerization of phospholamban to induce superinhibition of sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs) [17].

Associations of SLN with chemical compounds

• Elevated Ca(2+) dissociates both PLN and NF-SLN from their complexes with both SERCA1a and SERCA2a, but NF-SLN induced resistance to Ca(2+) dissociation of the PLN.SERCA complex [17].
• Analytical ultracentrifugation experiments revealed that SLN oligomerizes in the presence of the nonionic detergents octylpolyoxyethylene and octyl glucoside in a concentration-dependent manner [18].
• 2D solution NMR experiments were performed on SLN solubilized in sodium dodecyl sulfate (SDS) micelles [19].
• Systemic administration of L-696,418 significantly decreased loss of PG from cartilage and prevented the highly localized tissue degradation and the resultant changes in electromechanical behavior caused by intraarticular SLN injection [20].
• Inoculation of SLN, but not SHN, attenuated the nerve damage caused by PDX and protected foot sensory amplitude, H-wave amplitude, and behavioral measures of proprioceptive function [21].

Regulatory relationships of SLN

• Sarcolipin regulates the activity of SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+-ATPase [16].
• 3. Chol-but SLN inhibited O2-* production and myeloperoxidase release by PMNs evoked by FMLP, in a dose-dependent, but not time-dependent, manner and were more active than sodium butyrate [22].

Other interactions of SLN

• PLN mutations had more dramatic effects on SERCA1a coimmunoprecipitation than SLN mutations, suggesting that PLN dominates in the primary interaction with SERCA1a [8].
• Addition of the FLAG epitope to the highly conserved C terminus decreased the apparent affinity of SERCA1 for Ca2+ relative to native SLN and decreased Vmax significantly [16].
• Here is reviewed the assessed or suggested regulatory role of a family of small plasma/SR associated membrane proteins including gamma-subunit, phospholemman, Mat 8, KCNE (type 1, 2 and 3), RAMP (type 1, 2 and 3), sarcolipin and phospholamban, mainly found in muscular and vascular tissues [23].
• RESULTS: Relative expression levels of sarcolipin mRNA were significantly lower in MVD/AF (0.60 +/- 0.11) than in either MVD/NSR (1.28 +/- 0.17, P < 0.01) or controls (1.10 +/- 0.10, P < 0.05) [4].
• To characterize the effects of intraarticular injection of recombinant human stromelysin (SLN) on the matrix composition and physical properties of cartilage from lapine stifle joints and the modulation of these effects by the systemic administration of an N-carboxyalkyl synthetic matrix metalloproteinase inhibitor, L-696,418 [20].

Analytical, diagnostic and therapeutic context of SLN

• Immunofluorescence and immunoblotting of transfected cells by using anti-FLAG antibodies indicated that NF-SLN and PLN tagged at its N terminus with the FLAG epitope, even when overexpressed, were restricted to the ER [7].
• Circular dichroism spectroscopy showed that SLN is a predominantly alpha-helical protein and that the secondary structure is highly resistant to SDS and thermal denaturation [18].
• Western blotting showed expression and co-immunoprecipitation showed physical interaction between NF-SLN and SERCA2a [14].
• Overexpression of SLN resulted in significant reductions in both twitch and tetanic peak force amplitude and maximal rates of contraction and relaxation and increased fatigability with repeated electrical stimulation [24].
• Female 6-8-week-old New Zealand white rabbits received an intraarticular injection of 100 micrograms activated SLN in 1 stifle joint and buffer in the contralateral control knee; these animals were killed after 1 hour [20].

References