Cigarette smoke affects posttranslational modifications and inhibits capacitation-induced changes in human sperm proteins

Shrivastava, Vibha; Marmor, Hannah; Chernyak, Sholom; Goldstein, Marc; Feliciano, M.; Vigodner, Margarita

doi:10.1016/j.reprotox.2013.12.001

Cited by 18 publications

(8 citation statements)

References 28 publications

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“…Taken together with previously published data from our laboratory (Shrivastava et al, 2010, 2014), the results presented herein for testicular cells in vivo and in vitro demonstrate that cigarette smoke causes oxidative damage and changes in post-translation modifications of proteins, altered gene expression and molecular signaling in testicular cells. Future studies will focus on understanding the cell type-specific functions of CDK14 and its interacting partners, and the consequences of their downregulation during normal spermatogenesis and under stress.…”

Section: Resultssupporting

confidence: 86%

CDK14 expression is down-regulated by cigarette smoke in vivo and in vitro

et al. 2015

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In this study, DNA arrays have been employed to monitor gene expression patterns in testis of mice exposed to tobacco smoke for 24 weeks and compared to control animals. The results of the analysis revealed significant changes in expression of several genes that may have a role in spermatogenesis. Cdk14 was chosen for further characterization because of a suggested role in the testis and in regulation of Wnt signaling. RT-PCR analysis confirmed down regulation of Cdk14 in mice exposed to cigarette smoke (CS). Cdk14 is expressed in all testicular cells; spermatogonia- and Sertoli-derived cell lines treated with cigarette smoke extract (CSE) in vitro showed down-regulation of CDK14 mRNA and protein levels as well as down-regulation of β-catenin levels. CS-induced down-regulation of CDK14 mRNA and protein levels was also observed in several lung epithelium-derived cell lines including primary normal human bronchial epithelial cells (NHBE), suggesting that the effect is not restricted to the testis. Similar to testicular cells, CS-induced down-regulation of CDK14 in lung cells correlated with decreased levels of β-catenin, a finding suggesting impaired Wnt signaling. In the lungs, CDK14 was localized to the alveolar and bronchial epithelium.

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Section: Resultssupporting

confidence: 86%

CDK14 expression is down-regulated by cigarette smoke in vivo and in vitro

et al. 2015

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“…Recent studies from our group also revealed changes in global sumoylation following the induction of various stresses in germ cells and sperm (Shrivastava et al . 2010, Shrivastava et al . 2014).…”

Section: Introductionmentioning

confidence: 99%

Identification of cell-specific targets of sumoylation during mouse spermatogenesis

Xiao¹,

Pollack²,

Andrusier³

et al. 2016

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Recent findings suggest diverse and potentially multiple roles of SUMO in testicular function and spermatogenesis. However, SUMO targets remain uncharacterized in the testis due to the complex multicellular nature of testicular tissue, the inability to maintain and manipulate spermatogenesis in vitro, and the technical challenges involved in identifying low-abundance endogenous SUMO targets. In this study, we performed cell-specific identification of sumoylated proteins using concentrated cell lysates prepared with de-sumoylation inhibitors from freshly purified spermatocytes and spermatids. One-hundred and twenty proteins were uniquely identified in the spermatocyte and/or spermatid fractions. The identified proteins are involved in the regulation of transcription, stress response, microRNA biogenesis, regulation of major enzymatic pathways, nuclear-cytoplasmic transport, cell cycle control, acrosome biogenesis, and other processes. Several proteins with important roles during spermatogenesis were chosen for further characterization by co-immunoprecipitation, co-localization and in-vitro sumoylation studies. GPS-SUMO software was used to identify consensus and non-consensus sumoylation sites within the amino acid sequences of the proteins. The analyses confirmed the cell-specific sumoylation and/or SUMO interaction of several novel, previously uncharacterized SUMO targets such as CDK1, RNAP II, CDC5, MILI, DDX4, TDP-43 and STK31. Furthermore, several proteins that were previously identified as SUMO targets in somatic cells (e.g., KAP1, MDC1) were identified as SUMO targets in germ cells. Many of these proteins have a unique role in spermatogenesis and during meiotic progression. This research opens a novel avenue for further studies of SUMO at the level of individual targets.

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“…Oxidative stress influences various proteins and biological processes, and there was also cross-interaction between oxidative stress and SUMOylation (Rigato et al,2002;Feligioni et al, 2011;Leitao et al, 2011;Wu et al, 2015). The intensity of SUMOylation of many proteins was affected by oxidative stress (Shishido et al, 2008;Pandey et al, 2011;Shrivastava et al, 2014;Sahin et al, 2014). SUMOylation enhances the stability and activity of SERCA2a (Feligioni and Nistico, 2013).…”

Section: Discussionmentioning

confidence: 99%

Role of TG2-Mediated SERCA2 Serotonylation on Hypoxic Pulmonary Vein Remodeling

et al. 2020

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Sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) pumps take up Ca2+ from the cytoplasm to maintain the balance of intracellular Ca2+. A decline in expression or activity of SERCA results in persistent store-operated calcium entry (SOCE). In cardiomyocytes as well as vascular smooth muscle cells (SMCs), SERCA2 acts as an important regulator of calcium cycling. The purpose of this study is to identify and better understand the role of transglutaminases2 (TG2) as a key factor involved in SERCA2 serotonination (s-SERCA2) and to elucidate the underlying mechanism of action. Human pulmonary venous smooth muscle cell in normal pulmonary lobe were isolated and cultured in vitro. Establishment of hypoxic pulmonary hypertension model in wild type and TG2 knockout mice. SERCA2 serotonylation was analyzed by co-(immunoprecipitation) IP when the TG2 gene silenced or overexpressed under normoxia and hypoxia in vivo and in vitro. Intracellular calcium ion was measured by using Fluo-4AM probe under normoxia and hypoxia. Real-time (RT)-PCR and Western blot analyzed expression of TG2, TRPC1, and TRPC6 under normoxia and hypoxia. Bioactivity of cells were analyzed by using Cell Counting Kit (CCK)-8, flow cytometry, wound healing, RT-PCR, and Western blot under PST-2744 and cyclopiazonic acid. We confirmed that 1) hypoxia enhanced the expression and activity of TG2, and 2) hypoxia increased the basal intracellular Ca2+ concentration ([Ca2+]i) and SOCE through activating TRPC6 on human pulmonary vein smooth muscle cells (hPVSMC). Then, we investigated the effects of overexpression and downregulation of the TG2 gene on the activity of SERCA2, s-SERCA2, basal [Ca2+]i, and SOCE under normoxia and hypoxia in vitro, and investigated the activity of SERCA2 and s-SERCA2 in vivo, respectively. We confirmed that SERCA2 serotonylation inhibited the activity of SERCA2 and increased the Ca2+ influx, and that hypoxia induced TG2-mediated SERCA2 serotonylation both in vivo and in vitro. Furthermore, we investigated the effect of TG2 activity on the biological behavior of hPVSMC by using an inhibitor and agonist of SERCA2, respectively. Finally, we confirmed that chronic hypoxia cannot increase vessel wall thickness, the right ventricular systolic pressure (RVSP), and right ventricular hypertrophy index (RVHI) of vascular smooth muscle-specific Tgm2−/− mice. These results indicated that hypoxia promoted TG2-mediated SERCA2 serotonylation, thereby leading to inhibition of SERCA2 activity, which further increased the calcium influx through the TRPC6

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Cigarette smoke affects posttranslational modifications and inhibits capacitation-induced changes in human sperm proteins

Cited by 18 publications

References 28 publications

CDK14 expression is down-regulated by cigarette smoke in vivo and in vitro

CDK14 expression is down-regulated by cigarette smoke in vivo and in vitro

Identification of cell-specific targets of sumoylation during mouse spermatogenesis

Role of TG2-Mediated SERCA2 Serotonylation on Hypoxic Pulmonary Vein Remodeling

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