157 research outputs found
Skeletal Muscle Sorbitol Levels in Diabetic Rats with and without Insulin Therapy and Endurance Exercise Training
Sorbitol accumulation
is postulated to play a role in skeletal muscle
dysfunction associated with diabetes. The
purpose of this study was to determine the
effects of insulin and of endurance exercise on
skeletal muscle sorbitol levels in
streptozotocin-induced diabetic rats. Rats were
assigned to one experimental group (control
sedentary, control exercise, diabetic sedentary,
diabetic exercise, diabetic sedentary
no-insulin). Diabetic rats received daily
subcutaneous insulin. The exercise-trained rats
ran on a treadmill (1 hour, 5X/wk, for
12 weeks). Skeletal muscle sorbitol levels
were the highest in the diabetic sedentary
no-insulin group. Diabetic sedentary rats
receiving insulin had similar sorbitol levels to
control sedentary rats. Endurance exercise did
not significantly affect sorbitol levels. These
results indicate that insulin treatment lowers
sorbitol in skeletal muscle; therefore sorbitol
accumulation is probably not related to muscle
dysfunction in insulin-treated diabetic
individuals. Endurance exercise did not
influence intramuscular sorbitol values as
strongly as insulin
Convergent activation of two-pore channels mediated by the NAADP-binding proteins JPT2 and LSM12
The second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) evokes calcium ion (Ca2+) release from endosomes and lysosomes by activating two-pore channels (TPCs) on these organelles. Rather than directly binding to TPCs, NAADP associates with proteins that indirectly confer NAADP sensitivity to the TPC complex. We investigated whether and how the NAADP-binding proteins Jupiter microtubule-associated homolog 2 (JPT2) and like-Sm protein 12 (LSM12) contributed to NAADP-TPC-Ca2+ signaling in human cells. Biochemical and functional analyses revealed that recombinant JPT2 and LSM12 both bound to NAADP with high affinity and that endogenous JPT2 and LSM12 independently associated with TPC1 and TPC2. On the basis of knockout and rescue analyses, both NAADP-binding proteins were required to support NAADP-evoked Ca2+ signaling and contributed to endolysosomal trafficking of pseudotyped coronavirus particles. These data reveal that the NAADP-binding proteins JPT2 and LSM12 convergently regulate NAADP-evoked Ca2+ release and function through TPCs
Progesterone receptor membrane component 1 facilitates Ca²⺠signal amplification between endosomes and the endoplasmic reticulum
Membrane contact sites (MCSs) between endosomes and the endoplasmic reticulum (ER) are thought to act as specialized trigger zones for Ca2+ signaling, where local Ca2+ released via endolysosomal ion channels is amplified by ER Ca2+-sensitive Ca2+ channels into global Ca2+ signals. Such amplification is integral to the action of the second messenger, nicotinic acid adenine dinucleotide phosphate (NAADP). However, functional regulators of inter-organellar Ca2+ crosstalk between endosomes and the ER remain poorly defined. Here, we identify progesterone receptor membrane component 1 (PGRMC1), an ER transmembrane protein that undergoes a unique heme-dependent dimerization, as an interactor of the endosomal two pore channel, TPC1. NAADP-dependent Ca2+ signals were potentiated by PGRMC1 overexpression through enhanced functional coupling between endosomal and ER Ca2+ stores and inhibited upon PGRMC1 knockdown. Point mutants in PGMRC1 or pharmacological manipulations that reduced its interaction with TPC1 were without effect. PGRMC1 therefore serves as a TPC1 interactor that regulates ER-endosomal coupling with functional implications for cellular Ca2+ dynamics and potentially the distribution of heme
Consequences of sexual harassment in sport for female athletes
Sexual harassment research was first undertaken in the workplace and educational settings. Research on sexual harassment in sport is scarce but has grown steadily since the mid-1980s. Even so, very little is known about the causes and/or characteristics and/or consequences of sexual harassment in sport settings. This article reports on the findings from interviews with 25 elite female athletes in Norway who indicated in a prior survey (N =572) that they had experienced sexual harassment from someone in sport. The consequences of the incidents of sexual harassment that were reported were mostly negative, but some also reported that their experiences of sexual harassment had had no consequences for them. âThinking about the incidentsâ, a âdestroyed relationship to the coachâ, and âmore negative view of men in generalâ were the most often negative consequences mentioned. In addition, a surprising number had chosen to move to a different sport or to drop out of elite sport altogether because of the harassment
Aberrant Cyclization Affords a C-6 Modified Cyclic Adenosine 5â˛-Diphosphoribose Analogue with Biological Activity in Jurkat T Cells
*S Supporting Information ABSTRACT: Two nicotinamide adenine dinucleotide (NAD +) analogues modified at the 6 position of the purine ring were synthesized, and their substrate properties toward Aplysia californica ADP-ribosyl cyclase were investigated. 6-N-Methyl NAD + (6-N-methyl nicotinamide adenosine 5â˛-dinucleotide 10) hydrolyzes to give the linear 6-N-methyl ADPR (adenosine 5â˛-diphosphoribose, 11), whereas 6-thio NHD + (nicotinamide 6-mercaptopurine 5â˛-dinucleotide, 17) generates a cyclic dinucleotide. Surprisingly, NMR correlation spectra confirm this compound to be the N1 cyclic product 6-thio N1-cIDPR (6-thio cyclic inosine 5â˛-diphosphoribose, 3), although the corresponding 6-oxo analogue is well-known to cyclize at N7. In Jurkat T cells, unlike the parent cyclic inosine 5â˛-diphosphoribose N1-cIDPR 2, 6-thio N1-cIDPR antagonizes both cADPR- and N1cIDPR-induced Ca 2+ release but possesses weak agonist activity at higher concentration. 3 is thus identified as the first C-6 modified cADPR (cyclic adenosine 5â˛-diphosphoribose) analogue antagonist; it represents the first example of a fluorescent N1cyclized cADPR analogue and is a new pharmacological tool for intervention in the cADPR pathway of cellular signaling
Scholarship on Gender and Sport in Sex Roles and Beyond
In this paper we critically review how research on girls or women and sport has developed over the last 35Â years. We use a post-positivist lens to explore the content of the papers published in Sex Roles in the area of women, gender and sport and examine the shifts in how gender and sport have been conceptualized in these accounts. In order to initiate a broader dialogue about the scholarly analysis of gender and sport, we subsequently explore ideas inspired by feminist theorizing that have dominated/guided related research in other outlets over this time period but have received relatively little attention in papers published in Sex Roles. We conclude by briefly making suggestions for further research in this area
Broadâspecificity GH131 βâglucanases are a hallmark of fungi and oomycetes that colonize plants
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