Effects of Manganese and Other Divalent Cations on Progressive Motility of Human Sperm

Magnus, O; Brekke, I.; Åbyholm, Thomas; Purvis, K.

doi:10.3109/01485019008986875

Cited by 22 publications

(13 citation statements)

References 9 publications

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“…Activity had been described in the presence of other divalents, such as Co 2ϩ , Ca 2ϩ , and Mg 2ϩ , but Mn 2ϩ -dependent activity was always significantly higher (19,25,26). We purified the 48-kDa isoform of human sAC fused to GST and confirmed that its K m for ATPMn 2ϩ (ϳ0.8 mM) was indistinguishable from the value obtained for sAC activity purified from rat testis (14) and matched the values reported for soluble cAMP-producing activity in testis and sperm from a variety of mammals (11,21,27).…”

Section: Discussionmentioning

confidence: 99%

“…In this report we confirm that calcium directly stimulates sAC activity and that calcium functions independently from calmodulin to increase the affinity of sAC for its substrate ATP-Mg 2ϩ . Regulation by calcium, which is capable of supporting catalytic activity in the absence of Mg 2ϩ (19,25,26), suggests that sAC, like tmACs, utilizes two metals in its active site; however, the active center of sAC would function best with different metals. It is possible that Ca 2ϩ , which lowers the apparent K m for substrate ATP-Mg 2ϩ , would be better at coordinating ATP, while Mg 2ϩ would serve as the catalytic metal.…”

Section: Discussionmentioning

confidence: 99%

“…Historically, soluble adenylyl cyclase activity found in testis has been assayed in the presence of Mn 2ϩ (10); little or no in vitro activity was detected when Mg 2ϩ , Ca 2ϩ , or Co 2ϩ was used as the sole divalent (19,25,26). The K m for ATP-Mn 2ϩ of soluble AC activity from testis cytosol has been reported to be 1-2 mM (11,21,27).…”

Section: Atp-mnmentioning

confidence: 99%

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Kinetic Properties of “Soluble” Adenylyl Cyclase

Litvin

Kamenetsky

Zarifyan

et al. 2003

Journal of Biological Chemistry

308

156

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"Soluble" adenylyl cyclase (sAC) is a widely expressed source of cAMP in mammalian cells that is evolutionarily, structurally, and biochemically distinct from the G protein-responsive transmembrane adenylyl cyclases. In contrast to transmembrane adenylyl cyclases, sAC is insensitive to heterotrimeric G protein regulation and forskolin stimulation and is uniquely modulated by bicarbonate ions. Here we present the first report detailing kinetic analysis and biochemical properties of purified recombinant sAC. We confirm that bicarbonate regulation is conserved among mammalian sAC orthologs and demonstrate that bicarbonate stimulation is consistent with an increase in the V max of the enzyme with little effect on the apparent K m for substrate, ATPMg 2؉ . Bicarbonate can further increase sAC activity by relieving substrate inhibition. We also identify calcium as a direct modulator of sAC activity. In contrast to bicarbonate, calcium stimulates sAC activity by decreasing its apparent K m for ATP-Mg 2؉ . Because of their different mechanisms, calcium and bicarbonate synergistically activate sAC; therefore, small changes of either calcium or bicarbonate will lead to significant changes in cellular cAMP levels. Two types of adenylyl cyclase (AC)1 are ubiquitously expressed in mammalian cells, a well characterized gene family of transmembrane ACs (tmACs) and the recently discovered "soluble" AC (sAC). The tmACs are plasma membrane bound, and their activities are regulated by G proteins in response to extracellular stimuli such as neurotransmitters and hormones (reviewed in Ref. 1). In contrast, sAC is associated with various intracellular organelles, including mitochondria, centrioles, mitotic spindle, mid-bodies, and nuclei (2). sAC activity is modulated by bicarbonate (3) and, as shown in this report, by Ca 2ϩ ; regulation by these intracellular signaling molecules suggests that sAC mediates cAMP-dependent responses to intrinsic cellular changes (4, 5).The catalytic mechanism of tmACs has been determined from biochemical and crystallographic studies. tmACs convert ATP to cAMP using two-metal catalysis where one ion acts as a free metal and the other coordinates ATP in the active site (6, 7). Its activators, G␣ s subunit or forskolin, stimulate tmACs by allosteric modulation of the active site (8, 9). More than 25 years ago, when soluble AC activity was first discovered, it was predicted to be molecularly distinct from tmACs because its activity appeared to be dependent on the presence of the divalent cation, Mn 2ϩ , and it was insensitive to forskolin and G protein regulation (10 -12). These differential properties enabled purification (13) and cloning of sAC from rat testis (14). The sAC gene is indeed molecularly distinct from tmACs; it possesses no transmembrane domains, and its catalytic domains are more closely related to those of cyanobacterial ACs than to those from other eukaryotic ACs. The purified soluble AC exhibited ϳ10-fold lower affinity for substrate ATP relative to tmACs (tmAC K m for ATP-Mn 2ϩ is ϳ 100...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Kinetic Properties of “Soluble” Adenylyl Cyclase

Litvin

Kamenetsky

Zarifyan

et al. 2003

Journal of Biological Chemistry

308

156

View full text Add to dashboard Cite

show abstract

“…The literature about the effects of magnesium concentration on sperm parameters refers mostly to other than avian species. In humans, sperm cell motility was enhanced by 0.2−1.0mM of Mg 2+ , while higher concentration led to the same motility compared to control levels (Magnus et al, 1990). In sea urchin, as well as in humans, Mg 2+ has been found to increase viability of spermatozoa in dose-dependent manner (Dawson et al, 1998).…”

mentioning

confidence: 92%

Relationship of ejaculate quality and selected biochemical parameters of blood in cockerels of three laying lines

Jarinkovičová¹,

Máchal²,

Máchal³

et al. 2012

Czech J. Anim. Sci.

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In domestic fowl (Gallus gallus f. domestica), monitoring of both quantitative and qualitative parameters of ejaculates is an indispensable precondition of successful artificial insemination; on the basis of the obtained results it is then possible to select the individuals that produce sufficient amounts AbstRAct: Ejaculates and blood plasma were sampled from cocks of three laying lines: Barred Plymouth Rock (BPR), Sussex Light (SU), and Rhode Island Red (RIR). Ejaculates and blood plasma were sampled four times during the laying period of hens. The following ejaculate parameters were determined: sperm motility, concentrations of sperm cells, ejaculate volume. Sperm morphology was examined. In the blood samples, concentrations of glucose, cholesterol, creatinine, calcium, phosphorus, and magnesium were analysed. The motility of spermatozoa of the cocks was 47.0% (BPR), 47.7% (RIR), and 48.3% (SU), respectively. The highest volume of ejaculate was found in BPR line (0.66 cm 3 ), the lowest one in SU line (0.46 cm 3 , P ≤ 0.01); the highest sperm concentration was in SU line (2.46 × 10 6 /mm 3 ), the lowest one in RIR line (1.96 × 10 6 /mm 3 , P ≤ 0.01). The number of morphologically abnormal sperm cells was similar in all lines − 47.0% BPR, 47.7% RIR, and 48.3% SU, respectively. In general, the occurrence of defective spermatozoa was high in all three lines; the most frequent were tail defects (from 20.3 to 29.7%), while sperm cells with developmental anomalies were less frequent (only 0.3 to 0.4%). Calculated phenotypic correlation between sperm motility on the one hand and the occurrence of defective sperm cells on the other was negative (r p = −0.28, P ≤ 0.01), as well as the correlation between sperm motility and sperm numbers, and between sperm motility and ejaculate volume (r p = −0.28, P ≤ 0.01 and r p = −0.31, P ≤ 0.01, respectively). Negative correlations were found between the level of magnesium in blood plasma and numbers of morphologically defective spermatozoa in the ejaculate, defective heads and defective connecting pieces (r p = −0.33, P ≤ 0.01; r p = −0.23, P ≤ 0.05; and r p = −0.26, P ≤ 0.05). Level of magnesium was positively correlated to sperm motility (r p = 0.26, P ≤ 0.05). However, positive correlations existed between concentration of glucose in blood plasma of cocks and numbers of morphologically defective spermatozoa in sampled ejaculates (r p = 0.27, P ≤ 0.01). Our finding is in accordance with the results found in mammals and other animals, and it shows an important role of magnesium as a key contributor to the quality of ejaculate in aviary species, in our case in laying lines of domestic fowl (Gallus domesticus).

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“…It has been found that Mn 2+ supplementation stimulated adenylate cyclase (membrane bound enzyme) activity in sperm, which in turn enhanced the level of cAMP. 25,26 This increase in concentration of cAMP through a cascade of events phosphorylated the axonemal protein, which are involved in sperm motility. Therefore, in the present study, increase in hyperactivity with Mn 2+ (200 mM) supplementation is associated with adenylate cyclase activity.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant effect of Mn2+ on capacitation and acrosome reaction of fresh and chilled cattle bull semen

2012

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The aim of this paper was to investigate the antioxidant effect of Mn 2+ (200 mM) on the sperm capacitation and acrosome reaction of fresh and chilled cattle bull semen. It has been found that Mn 2+ supplementation improves (P≤0.05) the motility at 0, 2, 4 and 6 h of incubation. MDA (malondialdehyde), end product of lipid peroxidation, decreases significantly (P≤0.05) with the supplementation of manganese at 0-and 6-hr of incubation both in fresh and chilled semen. Manganese also increases acrosome reaction significantly (P≤0.05) both in fresh and chilled semen at 0, 4 and 6 h of incubation. Therefore, our findings suggest the role of Mn 2+ supplementation in improving the quality of cattle bull semen by its scavenging property i.e. reduction in the production of reactive oxygen species during its storage at 4°C or incubation at 37°C for capacitation.

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Effects of Manganese and Other Divalent Cations on Progressive Motility of Human Sperm

Cited by 22 publications

References 9 publications

Kinetic Properties of “Soluble” Adenylyl Cyclase

Kinetic Properties of “Soluble” Adenylyl Cyclase

Relationship of ejaculate quality and selected biochemical parameters of blood in cockerels of three laying lines

Antioxidant effect of Mn2+ on capacitation and acrosome reaction of fresh and chilled cattle bull semen

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