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1.
J Osteopath Med ; 122(9): 453-459, 2022 09 01.
Article in English | MEDLINE | ID: mdl-35491729

ABSTRACT

CONTEXT: The most common skeletal disease, osteoporosis, causes bone fragility due to decreased bone mass and bone microarchitecture destruction. The health belief model is often applied to asymptomatic, prevention-related diseases such as osteoporosis. Steps to mitigate the insidious nature of osteoporosis, including education, motivation, and monitoring of bone mineral density, must begin at an earlier age. OBJECTIVES: This study evaluates the knowledge and health beliefs surrounding osteoporosis in a population of males and females 35-50 years old to determine sex-based differences in osteoporosis knowledge and beliefs and to assess the correlation between perceptions and health motivation. METHODS: Participants (81 males, 92 females) completed two questionnaires: the Osteoporosis Knowledge Test and the Osteoporosis Health Belief Scale. Descriptive statistics were performed along with Pearson product-moment correlation analysis to determine the relationships between the variables. Sex-based differences were calculated utilizing independent t-tests. RESULTS: We discovered a statistically significant negative correlation between the barriers to exercise and health motivation (-0.434, p < 0.001) and a statistically significant positive correlation between the benefits of exercise and health motivation (0.385, p < 0.001). However, there was not a statistically significant correlation between health motivation with the following: the benefits of calcium, susceptibility, and the seriousness of osteoporosis. Between males and females, there was a statistically significant difference in exercise and calcium knowledge, susceptibility, and the benefits of both exercise and calcium (p < 0.05). CONCLUSIONS: Males and females 35-50 years old perceive themselves to have a low susceptibility to osteoporosis. They do not consider osteoporosis a serious disease and have little motivation to mitigate its inception or progression. Their perceptions show that barriers to exercise impact health motivation more than the perceived benefits of exercise.


Subject(s)
Calcium , Osteoporosis , Adult , Bone Density , Calcium, Dietary , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Osteoporosis/epidemiology
2.
J Strength Cond Res ; 35(1): 227-232, 2021 Jan 01.
Article in English | MEDLINE | ID: mdl-29239997

ABSTRACT

ABSTRACT: Giffin, KL, Knight, KB, Bass, MA, and Valliant, MW. Predisposing risk factors and stress fractures in collegiate cross-country runners. J Strength Cond Res 35(1): 227-232, 2021-The purpose of this study was to explore factors associated with increased stress fractures in collegiate cross-country runners. Subjects in this study were 42 male and female cross-country runners at a Division I university. Each athlete completed a questionnaire regarding smoking status, vitamin/mineral intake, previous stress fracture history, birth control usage, menstrual status, and demographic information. Nutritional assessment using a 3-day food record and measurements of whole body, lumbar spine, and hip bone mineral densities (BMDs) were also conducted on each athlete. Results indicated that 40% of the female and 35% of the male runners reported a history of stress fracture, and that all of them did not meet the recommended daily energy intake or adequate intakes for calcium or vitamin D required for their amount of training. Two-tailed t-test found statistically higher incidences of lumbar spine BMD in male and female runners whose daily calcium and vitamin D intakes were below minimum requirements as well as for women whose caloric intake was below the required level. When data on the lumbar spine was evaluated, 31% of subjects (31.8% of the male and 30% of the female runners) were identified as having osteopenia and 4.8% with osteoporosis. Results warrant a need for future longitudinal studies.


Subject(s)
Fractures, Stress , Bone Density , Calcium, Dietary , Female , Fractures, Stress/epidemiology , Fractures, Stress/etiology , Humans , Male , Risk Factors , Universities
3.
South Med J ; 113(10): 524-530, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33005971

ABSTRACT

OBJECTIVES: To observe the state of knowledge, attitudes, and beliefs regarding the effectiveness of the 2017-2018 H3N2 influenza virus vaccine in a representative sample of college students and determine how many students experienced flu-like symptoms, whether vaccinated or unvaccinated. METHODS: In March 2018, a 19-item survey related to the 2017-2018 flu virus vaccine was e-mailed to a random sample of 4961 rural southeastern university undergraduate and graduate students. A total of 634 students participated. RESULTS: Among 634 respondents, 37.5% received a flu vaccination. Knowledge about the flu was significantly associated with the decision to be vaccinated (χ2 = 18.68, P < 0.001). Of those who received the vaccine, 25.2% reported that they knew "a lot" about the flu. Approximately 28.8% of respondents believed the vaccine to be "very effective" (n = 145). CONCLUSION: Increased knowledge about the flu indicates an association with a higher rate of flu vaccinations among college students.


Subject(s)
Health Knowledge, Attitudes, Practice , Influenza A Virus, H3N2 Subtype , Influenza Vaccines/therapeutic use , Influenza, Human/prevention & control , Students/psychology , Adolescent , Adult , Female , Humans , Influenza, Human/virology , Male , Middle Aged , Patient Acceptance of Health Care/statistics & numerical data , Southeastern United States , Students/statistics & numerical data , Surveys and Questionnaires , Universities , Young Adult
4.
Health Promot Perspect ; 10(1): 59-65, 2020.
Article in English | MEDLINE | ID: mdl-32104658

ABSTRACT

Background: Among student populations, literature has identified associations between prescription opioid misuse and symptoms of depression such as hopelessness, sadness, and emotional pain. Thus far, existing literature has yet to investigate associations between prescription opioid misuse and depression using validated screening instruments for depression when exploring such associations. The purpose of this study was to utilize a validated screening tool to explore quantifiable presence of depression among college students who engage in recreational prescription opioid misuse (RPOM). Additionally, gender differences in depression and co-occurring substance use are examined. Methods: Students (n = 104) of a large university in the Southeastern United States who reported ROM within the past 6 months completed instrumentation assessing demographics, substance use, as well as, screening tools for depression and possible opioid use disorder (OUD). Results: Positive depression screens were significantly higher among females, however, nearly56% of participants screened positive for major depression. Though high levels of co-occurring substance use were observed among the entire sample, males were significantly more likely to report cocaine use, more frequent use of alcohol and marijuana, as well as, exhibit a positive screen for disordered opioid use, at a rate 5 times that of their female counterparts. Conclusion: Students who engage in RPOM are a particularly heightened-risk subsample of the college population who exhibit high levels of depressive symptomatology and substance use behavior. Targeted programming and further investigations are needed among this specific population. Future studies are encouraged to utilize validated instruments when assessing depression among students.

5.
J Am Osteopath Assoc ; 119(6): 357-363, 2019 Jun 01.
Article in English | MEDLINE | ID: mdl-31135863

ABSTRACT

CONTEXT: Osteoporosis is characterized by low bone mineral density (BMD) and has been thought to only be a major health concern for postmenopausal women. However, osteoporosis and its risk factors have been greatly understudied in the middle-aged and male populations. OBJECTIVE: To assess the likelihood of low BMD and its association with related risk factors in early-middle-aged (defined in this study as 35-50 years) men and women. METHODS: Eligible men and women completed a questionnaire assessing calcium intake, hours per week of exercise, and other related risk factors associated with osteoporosis and osteopenia. The primary outcome variable, BMD, was attained using dual-energy x-ray absorptiometry scans taken at the femoral neck, trochanter, intertrochanteric crest, total femur, and lumbar spine. RESULTS: Of the 173 participants in this study, 23 men (28%) and 24 women (26%) had osteopenia at the femoral neck. In men, there was a significant and negative correlation between exercise and femoral neck BMD (r=-0.296, P=.01). In women, correlation analyses showed significant positive correlations between exercise and BMD of the trochanter (r=0.329, P=.003), intertrochanteric crest (r=0.285, P=.01), total femur (r=0.30, P=.01), and lumbar spine (r=0.29, P=.01). CONCLUSIONS: Osteopenia was found in more than 25% of both male and female participants, which suggests that more osteoporosis screening and prevention programs need to be targeted to persons in the studied age group because osteopenia can lead to osteoporosis.


Subject(s)
Bone Density , Absorptiometry, Photon , Adult , Age Factors , Body Mass Index , Cross-Sectional Studies , Female , Hip/diagnostic imaging , Humans , Lumbar Vertebrae/diagnostic imaging , Male , Middle Aged , Risk Factors , Sex Factors , Surveys and Questionnaires
6.
J Res Health Sci ; 16(4): 228-232, 2016.
Article in English | MEDLINE | ID: mdl-28087857

ABSTRACT

BACKGROUND: Osteoporosis is a systemic skeletal disorder characterized by low bone mineral density (BMD) that leads to an increase in bone fragility, causing an individual to be at an increased risk for fractures. Asian-Indians are at an increased risk for developing osteoporosis. Considering the number of Asian-Indians in the US is rapidly growing, they likely could be an underappreciated population at risk for bone fractures. The aim of this study was to investigate bone health and determine the factors affecting BMD in Asian-Indians living in the US. METHODS: Asian-Indians residing in Northern Mississippi (n = 87) were enrolled in this cross-sectional study from June 2013 to August 2014. Eligible participants completed a self-administered Osteoporosis Risk Factor Assessment questionnaire. BMD and body composition were measured using a dual energy x-ray absorptiometry scan (DXA). RESULTS: Eight-seven Asian-Indians (male: 62.1%) participated, with the average age being 28.49 yr old (SD = 6.62). Overall, 31.0% and 48.3% had low femoral neck BMD and spinal BMD, respectively. Multiple regression analysis revealed that age, percent body fat, and body mass index (BMI) significantly predicted BMD at femur neck (P<0.05). Additionally, percent body fat, BMI, childhood milk consumption, and gender were statistically significant predictors of spinal BMD (P<0.05). CONCLUSIONS: The findings from this study should be beneficial to healthcare providers that work with Asian-Indian population groups. Health promotion programs focusing on osteoporosis prevention are needed among Asian-Indians to prevent the risk of fractures.


Subject(s)
Adipose Tissue/metabolism , Asian People , Body Composition , Body Mass Index , Bone Density , Bone and Bones/metabolism , Osteoporosis , Adolescent , Adult , Animals , Child , Cross-Sectional Studies , Feeding Behavior , Female , Femur Neck/metabolism , Humans , India/ethnology , Male , Middle Aged , Milk , Mississippi/epidemiology , Osteoporosis/ethnology , Osteoporosis/etiology , Pilot Projects , Spine/metabolism , Young Adult
7.
J Cancer Res Clin Oncol ; 142(6): 1273-83, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26642962

ABSTRACT

PURPOSE: This systematic review was conducted to evaluate and summarize the existing literature on prevalence of ultraviolet radiation (UVR) exposure, sun protection, and screening behaviors among individuals diagnosed with malignant melanoma (MM). METHODS: The search was performed in PubMed, CINAHL, PsycINFO, ScienceDirect, EMBASE, and ERIC from inception of each database through July 2014. Studies were included if (1) individuals diagnosed with MM were the primary sample, (2) measured UVR exposure, primary and secondary preventive behaviors, (3) original research communication that constitutes an entire set of empirical data, (4) observational design, and (5) English peer-reviewed. Studies were excluded if (1) all of the inclusion criteria were not met and (2) duplicates, conference abstracts, editorials, news, letters to the editor, comments, reviews, feature articles, white papers, and guidelines. RESULTS: The search resulted in 255 articles that were screened for relevance; however, only 15 articles met all of the inclusion criteria. Most of the studies were cross-sectional (n = 10), used self-administered surveys (n = 8), and were conducted in North America (n = 10). The sample sizes ranged considerably, but were mostly Caucasian (n = 6) and included a higher proportion of women (n = 8). Evidence demonstrated that individuals with MM still engaged in sunbathing, indoor tanning, and reported sunburns. Moreover, survivors reported inadequate levels of both sun protection and skin self-examinations. CONCLUSIONS: The findings highlight the need for intensifying intervention strategies to reduce the risk of new primary MMs in this group. Future research should increase in rigor and include more diverse populations and regions.


Subject(s)
Health Behavior , Melanoma/pathology , Skin Neoplasms/prevention & control , Survivors , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Sunlight
8.
Article in English | MEDLINE | ID: mdl-26515833

ABSTRACT

Compared to the general population, the risk of developing non-melanoma skin cancer is considerably higher among individuals with a previous history of this condition. Protection from ultraviolet (UV) radiation is the primary evidence-based approach for minimizing this risk. This review was aimed to assess the prevalence of sun-safe behaviors in non-melanoma skin cancer survivors. Searches were conducted in six electronic databases including PubMed, Psyclnfo, CINAHL, EMBASE, ERIC and Science Direct. A narrative approach was adopted to synthesize the data. The findings demonstrated that respondents do not protect themselves optimally from UV radiation exposure. Low levels of perceived skin cancer risk, a lack of knowledge about effective sun protection strategies and the inconvenience associated with sun-safe behaviors appear to explain this finding. A note of caution is required here, as there is a potential for publication bias. Moreover, the results of this study cannot be generalized to all non-melanoma skin cancer patients. Skin cancer survivors must be educated about their increased risk of future skin cancers. Behavioral interventions must be developed to increase the adoption of skin protective behaviors in this high-risk population group.


Subject(s)
Carcinoma, Basal Cell/psychology , Carcinoma, Squamous Cell/psychology , Health Behavior , Skin Neoplasms/psychology , Carcinoma, Basal Cell/diagnosis , Carcinoma, Basal Cell/prevention & control , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/prevention & control , Health Knowledge, Attitudes, Practice , Humans , Protective Clothing , Skin Neoplasms/diagnosis , Skin Neoplasms/prevention & control , Sunscreening Agents/therapeutic use
9.
Health Promot Perspect ; 5(2): 147-52, 2015.
Article in English | MEDLINE | ID: mdl-26290830

ABSTRACT

BACKGROUND: Persons with intellectual/developmental disabilities (IDD) are exposed to several factors, which have been determined as risks for osteoporosis. Many of these individuals are non-ambulatory, resulting in lack of weight bearing activity, which is well established as a major contributor to bone loss. The purpose of this study was to investigate risk factors for low bone mineral density (BMD) in persons with IDD residing in residential facilities. METHODS: This cross-sectional study was conducted at an Intermediate Care Facility for individuals with Intellectual and Developmental Disabilities (ICF/IDD). Medical records data were used from 69 individuals, including heal scan T-scores, nutritional, pharmacologic and other risk factors. Chi-Square analysis was used to determine relationships between the variables. RESULTS: BMD measures were not significantly associated with age, gender, height, weight, or BMI for this population (P > 0.05). The association between BMD diagnoses and DSM-IV classification of mental retardation approached significance (P = 0.063). A significant association was found with anti-seizure medication (P = 0.009). CONCLUSION: Follow-up studies should focus on how supplementation and medication changes may or may not alter BMD. Persons with IDD are experiencing longer life expectancies, and therefore, studies ascertaining information on diseases associated with this aging population are warranted.

10.
Ultrasound Med Biol ; 41(2): 557-64, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25444689

ABSTRACT

To test the validity of published equations, 79 Caucasian adults (40 men and 39 women) aged 50-78 y had muscle thickness (MT) measured by ultrasound at nine sites of the body. Fat-free mass (FFM), lean soft tissue mass (LM) and total muscle mass (TMM) were estimated from MT using equations previously published in the literature. Appendicular LM (aLM) was estimated using dual-energy X-ray absorptiometry (DXA) and this method served as the reference criterion. There were strong correlations (range r = 0.85-0.94) between DXA-derived aLM and estimated FFM, leg LM or TMM. Total error between DXA-derived aLM and TMM (∼2 kg) was lower compared with the three other selected equations (6-10 kg). A Bland-Altman plot revealed that there was no systematic bias between aLM and TMM; however, the other three equations included systematic error. Our results suggest that an ultrasound equation for TMM is appropriate and useful for evaluating skeletal muscle mass in the body.


Subject(s)
Body Composition , Muscle, Skeletal/diagnostic imaging , Abdomen/diagnostic imaging , Absorptiometry, Photon , Adipose Tissue/diagnostic imaging , Aged , Arm/diagnostic imaging , Body Mass Index , Female , Humans , Leg/diagnostic imaging , Male , Middle Aged , Predictive Value of Tests , Reproducibility of Results , Ultrasonography
11.
Environ Health Prev Med ; 19(6): 467-74, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25271053

ABSTRACT

OBJECTIVES: Considering the potential for occupational sun exposure among state park workers, the purpose of this pilot study was to identify skin cancer knowledge, health beliefs, self-efficacy, and sun protection behaviors (SPBs) among state park employees. METHODS: The current study used a cross-sectional survey research design with state park workers in a Southern state. Of the 94 possible employees who could have participated in the study, 87 completed the survey. RESULTS: Assessment of the participants' skin cancer knowledge demonstrated an average correct response rate of 68.8 %. While the vast majority (87.4 %) believed that skin cancer is a serious disease, a minority (42.5 %) believed they would develop skin cancer sometime during their lifetime, and even fewer (35.6 %) believed their risk was higher than average. Collectively, workers reported low levels of SPBs. The most commonly reported barriers to sun protection were "inconvenient," "too hot to wear," and "forget to protect." Half of the participants (50.6 %) were highly confident in their ability to wear long pants while in the sun. About the same proportion of participants was highly confident they could wear a wide-brimmed hat (21.8 %) and sunscreen (20.7 %). CONCLUSIONS: Based on available evidence, a need exists to develop individual and worksite programs and interventions to increase skin cancer prevention behaviors among this occupational group. This data could serve as a baseline to monitor and evaluate the efficacy of these interventions.


Subject(s)
Health Knowledge, Attitudes, Practice , Occupational Diseases/prevention & control , Skin Neoplasms/prevention & control , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Pilot Projects , Protective Clothing/statistics & numerical data , Risk Factors , Self Efficacy , Sunburn/prevention & control , Sunscreening Agents/therapeutic use , Surveys and Questionnaires
12.
J Skin Cancer ; 2014: 248198, 2014.
Article in English | MEDLINE | ID: mdl-24782927

ABSTRACT

Outdoor athletes represent an important group at risk for skin cancer because they are routinely exposed to high levels of ultraviolet radiation. The purpose of this study was to assess current skin cancer knowledge, attitudes, and behaviors among collegiate athletes. A modified version of the Melanoma Risk Behavior Survey was completed by 343 athletes attending a Southern University in the USA, generating an 87% response rate. Survey results demonstrated that the majority of the athletes do not limit their sun exposure and reported low levels of sun protective behaviors. In addition, athletes lacked knowledge about skin cancer and sun protection. Eighty-three percent of the athletes stated that tanning beds improve one's overall health. Race was significantly associated with skin cancer knowledge, whereas, gender was found to be significantly associated with knowledge, attitudes, and behaviors towards skin cancer. Additionally, there was a significant relationship between knowledge and behavior, but not between attitude and behavior. This study highlights the need to educate athletes about the hazards of tanning to minimize UV exposure and promote sun protection habits. Moreover, athletes should be educated on the dangers of indoor tanning facilities and encouraged to avoid these facilities.

13.
Rejuvenation Res ; 17(3): 291-6, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24460174

ABSTRACT

Exercise mode and intensity/duration are important factors for influencing muscle morphology and function as well as bone. However, it is unknown whether masters cyclists who undergo regular moderate- to high-intensity exercise maintain lower-body skeletal muscle mass (SM) and function and bone health when compared with young adults. The purpose of this study was to compare SM, areal bone mineral density (aBMD), and gait performance between masters cyclists and young adults. Fourteen male masters cyclists (aged 53-71 years) and 13 moderately active young men (aged 20-30 years, exercising less than twice a week) volunteered. The masters cyclists were all training actively (four to five times per week, ∼200 miles per week) for on average the last 17 years (range 7-38 years). Thigh SM was estimated from an ultrasound-derived prediction equation using muscle thickness (MTH). Appendicular lean mass (aLM) and aBMD were also estimated using dual-energy X-ray absorptiometry. There were no significant differences (p<0.05) in thigh SM, anterior and posterior thigh MTH ratio, or aLM between masters cyclists and young men. Maximum straight and zigzag walking times were also similar between groups. Lumbar spine (L1-L4) aBMD was not different between groups, but femoral neck aBMD was lower (p<0.05) in the cyclists than in the young men. Our results suggest that appendicular as well as site-specific thigh muscle loss with aging were not observed in masters cyclists. This maintenance of muscle mass in masters cyclists may preserve walking performance to similar levels as moderately active young adults. However, long-term cycling does not preserve femoral neck aBMD.


Subject(s)
Bicycling , Bone Density , Muscle, Skeletal/anatomy & histology , Organ Size , Walking , Adult , Humans , Male , Young Adult
14.
Dermatol Res Pract ; 2013: 496913, 2013.
Article in English | MEDLINE | ID: mdl-24223037

ABSTRACT

There are slightly over one million workers in the landscape service industry in the US. These workers have potential for high levels of solar ultraviolet radiation exposure, increasing their risk of skin cancer. A cross-sectional sample of 109 landscapers completed a self-administered questionnaire based on Health Belief Model (HBM). The participants correctly answered 67.1% of the knowledge questions, 69.7% believed they were more likely than the average person to get skin cancer, and 87.2% perceived skin cancer as a severe disease. Participants believed that the use of wide-brimmed hats, long sleeved shirts/long pants, and sunscreen was beneficial but reported low usage of these and other sun protective strategies. The primary barriers to using sun protection were "I forget to wear it" and "it is too hot to wear." Of the HBM variables, perceived benefits outweighing perceived barrier (r = .285, P = .003) and self-efficacy (r = .538, P = .001) were correlated with sun protection behaviors. The reasons for absence of the relationship between perceived skin cancer threat and sun protection behaviors could be lack of skin cancer knowledge and low rate of personal skin cancer history.

15.
J Skin Cancer ; 2013: 453174, 2013.
Article in English | MEDLINE | ID: mdl-24251040

ABSTRACT

Outdoor workers are at a higher risk for developing skin cancer due to their increased sun exposure. The primary objective of this review was to synthesize the current research literature that addresses sociodemographic and psychological factors related to sun protection behaviors in outdoor workers. Two additional purposes were to provide an overview of sun exposure and describe sun protection behaviors of outdoor workers. To identify the studies for this review, a methodical search was performed in the PubMed, PsycInfo, MEDLINE, and ERIC databases. Fifteen studies met the review criteria. Despite regular and prolonged sun exposure, many outdoor workers fail to engage in sufficient sun protection behaviors. Correlates of outdoor workers' sun protection behaviors include being female, older age, being white, personal skin cancer history, time (hours/years) spent at work, sun safety training, perceived prioritization of sun protection, concern about sun exposure, workplace support, families' expectations, and familial information giving. However, limited attention is given to designing theoretically grounded studies to identify factors to inform future research. There is a need to conduct research based on solid theoretical foundations that explains the relationships among the factors in this domain.

16.
J Biol Chem ; 286(28): 24806-18, 2011 Jul 15.
Article in English | MEDLINE | ID: mdl-21610080

ABSTRACT

The densin C-terminal domain can target Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα) in cells. Although the C-terminal domain selectively binds CaMKIIα in vitro, full-length densin associates with CaMKIIα or CaMKIIß in brain extracts and in transfected HEK293 cells. This interaction requires a second central CaMKII binding site, the densin-IN domain, and an "open" activated CaMKII conformation caused by Ca(2+)/calmodulin binding, autophosphorylation at Thr-286/287, or mutation of Thr-286/287 to Asp. Mutations in the densin-IN domain (L815E) or in the CaMKIIα/ß catalytic domain (I205/206K) disrupt the interaction. The amino acid sequence of the densin-IN domain is similar to the CaMKII inhibitor protein, CaMKIIN, and a CaMKIIN peptide competitively blocks CaMKII binding to densin. CaMKII is inhibited by both CaMKIIN and the densin-IN domain, but the inhibition by densin is substrate-selective. Phosphorylation of a model peptide substrate, syntide-2, or of Ser-831 in AMPA receptor GluA1 subunits is fully inhibited by densin. However, CaMKII phosphorylation of Ser-1303 in NMDA receptor GluN2B subunits is not effectively inhibited by densin in vitro or in intact cells. Thus, densin can target multiple CaMKII isoforms to differentially modulate phosphorylation of physiologically relevant downstream targets.


Subject(s)
Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Calcium/metabolism , Calmodulin/metabolism , Receptors, AMPA/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Sialoglycoproteins/metabolism , Xenopus Proteins/metabolism , Animals , Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics , Calmodulin/genetics , Humans , Isoenzymes/genetics , Isoenzymes/metabolism , Mice , Mutation , Phosphorylation/physiology , Protein Structure, Tertiary , Rats , Receptors, AMPA/genetics , Receptors, N-Methyl-D-Aspartate/genetics , Sialoglycoproteins/genetics , Swine , Xenopus Proteins/genetics , Xenopus laevis
17.
J Biol Chem ; 283(21): 14286-94, 2008 May 23.
Article in English | MEDLINE | ID: mdl-18372251

ABSTRACT

Sustained nigrostriatal dopamine depletion increases the serine/threonine phosphorylation of multiple striatal proteins that play a role in corticostriatal synaptic plasticity, including Thr(286) phosphorylation of calcium/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha). Mechanisms underlying these changes are unclear, but protein phosphatases play a critical role in the acute modulation of striatal protein phosphorylation. Here we show that dopamine depletion for periods ranging from 3 weeks to 10 months significantly reduces the total activity of protein phosphatase (PP) 1, but not of PP2A, in whole lysates of rat striatum, as measured using multiple substrates, including Thr(286)-autophosphorylated CaMKIIalpha. Striatal PP1 activity is partially inhibited by a fragment of the PP1-binding protein neurabin-I, Nb-(146-493), because of the selective inhibition of the PP1gamma(1) isoform. The fraction of PP1 activity that is insensitive to Nb-(146-493) was unaffected by dopamine depletion, demonstrating that dopamine depletion specifically reduces the activity of PP1 isoforms that are sensitive to Nb-(146-493) (i.e. PP1gamma(1)). However, total striatal levels of PP1gamma(1) or any other PP1 isoform were unaffected by dopamine depletion, and our previous studies showed that total levels of the PP1 regulatory/targeting proteins DARPP-32, spinophilin, and neurabin were also unchanged. Rather, co-immunoprecipitation experiments demonstrated that dopamine depletion increases the association of PP1gamma(1) with spinophilin in striatal extracts. In combination, these data demonstrate that striatal dopamine depletion inhibits a specific synaptic phosphatase by increasing PP1gamma(1) interaction with spinophilin, perhaps contributing to hyperphosphorylation of synaptic proteins and disruptions of synaptic plasticity and/or dendritic morphology.


Subject(s)
Microfilament Proteins/pharmacology , Nerve Tissue Proteins/pharmacology , Parkinson Disease/enzymology , Protein Phosphatase 1/metabolism , Animals , Catalytic Domain , Disease Models, Animal , Dopamine/pharmacology , Enzyme Activation/drug effects , Isoenzymes/metabolism , Male , Peptide Fragments/pharmacology , Phosphorylation/drug effects , Rats , Rats, Sprague-Dawley
18.
J Neurochem ; 105(5): 1746-60, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18248607

ABSTRACT

Densin is a member of the leucine-rich repeat (LRR) and PDZ domain (LAP) protein family that binds several signaling molecules via its C-terminal domains, including calcium/calmodulin-dependent protein kinase II (CaMKII). In this study, we identify several novel mRNA splice variants of densin that are differentially expressed during development. The novel variants share the LRR domain but are either prematurely truncated or contain internal deletions relative to mature variants of the protein (180 kDa), thus removing key protein-protein interaction domains. For example, CaMKIIalpha coimmunoprecipitates with densin splice variants containing an intact C-terminal domain from lysates of transfected HEK293 cells, but not with variants that only contain N-terminal domains. Immunoblot analyses using antibodies to peptide epitopes in the N- and C- terminal domains of densin are consistent with developmental regulation of splice variant expression in brain. Moreover, putative splice variants display different subcellular fractionation patterns in brain extracts. Expression of green fluorescent protein (GFP)-fused densin splice variants in HEK293 cells shows that the LRR domain can target densin to a plasma membrane-associated compartment, but that the splice variants are differentially localized and have potentially distinct effects on cell morphology. In combination, these data show that densin splice variants have distinct functional characteristics suggesting multiple roles during neuronal development.


Subject(s)
Alternative Splicing/physiology , Brain/growth & development , Brain/metabolism , Protein Interaction Domains and Motifs/physiology , Sialoglycoproteins/genetics , Sialoglycoproteins/metabolism , Animals , Cell Line , Gene Expression Regulation, Developmental , Humans , Rats , Sialoglycoproteins/physiology , Subcellular Fractions/metabolism
19.
FASEB J ; 22(6): 1660-71, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18216290

ABSTRACT

Protein phosphatase 1 (PP1) catalytic subunits dephosphorylate specific substrates in discrete subcellular compartments to modulate many cellular processes. Canonical PP1-binding motifs (R/K-V/I-X-F) in a family of proteins mediate subcellular targeting, and the amino acids that form the binding pocket for the canonical motif are identical in all PP1 isoforms. However, PP1gamma1 but not PP1beta is selectively localized to F-actin-rich dendritic spines in neurons. Although the F-actin-binding proteins neurabin I and spinophilin (neurabin II) also bind PP1, their role in PP1 isoform selective targeting in intact cells is poorly understood. We show here that spinophilin selectively targets PP1gamma1, but not PP1beta, to F-actin-rich cortical regions of intact cells. Mutation of a PP1gamma1 selectivity determinant (N(464)EDYDRR(470) in spinophilin: conserved as residues 473-479 in neurabin) to VKDYDTW severely attenuated PP1gamma1 interactions with neurabins in vitro and in cells and disrupted PP1gamma1 targeting to F-actin. This domain is not involved in the weaker interactions of neurabins with PP1beta. In contrast, mutation of the canonical PP1-binding motif attenuated interactions of neurabins with both isoforms. Thus, selective targeting of PP1gamma1 to F-actin by neurabins in intact cells requires both the canonical PP1-binding motif and an auxiliary PP1gamma1-selectivity determinant.


Subject(s)
Actins/metabolism , Protein Phosphatase 1/metabolism , Amino Acid Sequence , Animals , Binding Sites , Brain/cytology , Brain/metabolism , Catalysis , Cell Line , Humans , Protein Binding , Protein Phosphatase 1/chemistry , Protein Phosphatase 1/genetics , Protein Structure, Tertiary , Protein Subunits , Rats , Transfection
20.
J Mol Cell Cardiol ; 44(2): 405-10, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18048055

ABSTRACT

Transgenic expression of enhanced green fluorescent protein (eGFP) in myocardium can result in cardiac dysfunction and cardiomyopathy, presumably through toxic effects that disrupt normal cellular signaling. The multifunctional Ca(2+)- and calmodulin-dependent protein kinase II (CaMKII) is widely expressed in myocardium and CaMKII activity is increased in human and animal models of cardiomyopathy, so we hypothesized that increased CaMKII activity is important for cardiomyopathy due to transgenic expression of eGFP. Here we report that cardiomyocyte-delimited eGFP over-expression causes increased CaMKII activity that predicts left ventricular dilation and dysfunction. On the other hand, transgenic co-expression of a CaMKII inhibitory peptide with eGFP prevents eGFP-mediated left ventricular dilation and dysfunction. These findings suggest that increased CaMKII activity is a critical pathological signal in transgenic cardiomyopathy due to eGFP over-expression.


Subject(s)
Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & inhibitors , Cardiomyopathies/enzymology , Green Fluorescent Proteins/metabolism , Animals , Cardiomyopathies/physiopathology , Heart Ventricles/drug effects , Heart Ventricles/pathology , Heart Ventricles/physiopathology , Hypertrophy , Mice , Mice, Transgenic , Organ Size/drug effects , Peptides/pharmacology , Ventricular Function, Left/drug effects
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