Onion (Allium cepa
 L.) peel extract (OPE) regulates human sperm motility via protein kinase C-mediated activation of the human voltage-gated proton channel

Abstract Background ADP-ribosylation is a ubiquitous post-translational modification that involves both mono- and poly-ADP-ribosylation. ARTD10, also known as PARP10, mediates mono-ADP-ribosylation (MARylation) of substrate proteins. A previous screen identified protein kinase C delta (PKCδ) as a potential ARTD10 substrate, among several other kinases. The voltage-gated K+ channel Kv1.1 constitutes one of the dominant Kv channels in neurons of the central nervous system and the inactivation properties of Kv1.1 are modulated by PKC. In this study, we addressed the role of ARTD10-PKCδ as a regulator of Kv1.1. Results We found that ARTD10 inhibited PKCδ, which increased Kv1.1 current amplitude and the proportion of the inactivating current component in HeLa cells, indicating that ARTD10 regulates Kv1.1 in living cells. An inhibitor of ARTD10, OUL35, significantly decreased peak amplitude together with the proportion of the inactivating current component of Kv1.1-containing channels in primary hippocampal neurons, demonstrating that the ARTD10-PKCδ signaling cascade regulates native Kv1.1. Moreover, we show that the pharmacological blockade of ARTD10 increases excitability of hippocampal neurons. Conclusions Our results, for the first time, suggest that MARylation by ARTD10 controls neuronal excitability.

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Protein kinase C is present in human sperm: possible role in flagellar motility.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.87.18.7305 ◽

1990 ◽

Vol 87 (18) ◽

pp. 7305-7308 ◽

Cited By ~ 57

Author(s):

R Rotem ◽

G F Paz ◽

Z T Homonnai ◽

M Kalina ◽

Z Naor

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Human Sperm ◽

Flagellar Motility ◽

Kinase C

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Ultrastructural localization of protein kinase C in human sperm.

Journal of Histochemistry & Cytochemistry ◽

10.1177/43.4.7897184 ◽

1995 ◽

Vol 43 (4) ◽

pp. 439-445 ◽

Cited By ~ 14

Author(s):

M Kalina ◽

R Socher ◽

R Rotem ◽

Z Naor

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Human Sperm ◽

Ultrastructural Localization ◽

Ultrastructural Level ◽

Sperm Head ◽

Structural Elements ◽

Kinase C ◽

Outer Dense Fibers ◽

Pkc Alpha

We localized protein kinase C (PKC) in human sperm cells at the ultrastructural level by the immunogold technique. The sperm head PKC was localized in the acrosome, equatorial segment, and post-acrosomal region. In the flagellum, PKC was associated with the segmented column of the neck and was distributed along the mid, principal, and end pieces. Immunoreactive sites were observed in patches along the axoneme and outer dense fibers and were evenly distributed between these regions. Pre-absorption of the antibody used with rat brain PKC (alpha and beta) eliminated gold labeling of the sperm head but only reduced labeling of the sperm tail. The co-localization of PKC with various cytoskeletal and other structural elements suggests that the proteins involved are potential substrates for sperm PKC subspecies. The localization of PKC in distinct structures of the human sperm (head, neck, and tail) strongly suggests a role for this enzyme in various aspects of sperm physiology.

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The Positive Inotropic and Calcium-Mobilizing Effects of Growth Hormone-Releasing Peptides on Rat Heart

Endocrinology ◽

10.1210/en.2003-0025 ◽

2003 ◽

Vol 144 (11) ◽

pp. 5050-5057 ◽

Cited By ~ 13

Author(s):

Xiang-Bin Xu ◽

Ji-Min Cao ◽

Jing-Jiang Pang ◽

Rong-Kun Xu ◽

Chao Ni ◽

...

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Ventricular Myocytes ◽

Phase 1 ◽

Dependent Manner ◽

Phase 2 ◽

Perfused Heart ◽

Voltage Gated ◽

Kinase C ◽

Phase Phase

Abstract GH-releasing peptides (GHRP) are synthetic peptides exerting GH-dependent or GH-independent effects via GH secretagogue receptor on many organs, including the heart. The underlying mechanisms of the cardiotropic properties of GHRP are poorly understood. This study investigates these effects of four GHRP in isolated perfused heart preparations and isolated neonatal and adult ventricular myocytes. The calcium response of cardiocytes to GHRP was visualized using confocal microscopy. All tested GHRP facilitated both ventricular contraction and relaxation in a dose-dependent manner, moderately decreasing coronary flow, but not modifying heart rate. GHRP induced a biphasic increase in intracellular free Ca2+ of the cardiocytes, consisting of a transient phase (phase 1), followed by a plateau phase (phase 2). Phase 1 was abolished by pretreatment with thapsigargin, a Ca2+-adenosine triphosphatase inhibitor of the sarcoplasmic reticulum. The phase 2 response was eliminated by removing extracellular free Ca2+, by verapamil, a voltage-gated Ca2+ channel blocker, or by 24-h pretreatment with phorbol 12-myristate 13-acetate, down-regulating protein kinase C. In isolated (denervated) heart, GHRP have a direct cardiotropic, without chronotropic, effect. GHRP elevate myocardial intracellular free Ca2+ through activating Ca2+ influx via voltage-gated Ca2+ channels and triggering Ca2+ release from thapsigargin-sensitive intracellular Ca2+ stores. Protein kinase C mediates the GHRP-induced Ca2+ influx, but not Ca2+ release. These finding support a number of roles for GHRP in the cardiovascular system.

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