Golnaz Golnarnik

• Golnarnik, Golnaz; Nieminen, Anni I.; Søland, Tine Merete; Galtung, Hilde & Haug, Trude M. (2026). Differential metabolic responses to hydrogen peroxide-induced oxidative stress in parotid and submandibular gland acinar cell lines. Biochemistry and Biophysics Reports. 46, s. 102596–102596. doi: 10.1016/j.bbrep.2026.102596. Fulltekst i vitenarkiv
• Golnarnik, Golnaz; Thiede, Bernd; Søland, Tine Merete; Galtung, Hilde & Haug, Trude Marie (2025). Hydrogen peroxide-induced oxidative stress alters protein expression in two rat salivary acinar cell lines. Archives of Oral Biology. ISSN 0003-9969. 175. doi: 10.1016/j.archoralbio.2025.106254. Fulltekst i vitenarkiv Vis sammendrag

  Objectives: This study aimed to investigate the impact of hydrogen peroxide-induced oxidative stress on the protein expression profiles of submandibular and parotid acinar cells using a proteomic approach. We sought to evaluate how oxidative stress might contribute to salivary gland dysfunction and whether the two glands respond differently.<p> <p>Design: Immortalized rat parotid gland (PG) and submandibular gland (SMG) acinar epithelial cell lines were exposed to 50 µM and 150 µM hydrogen peroxide for 24 hr, followed by protein identification and quantification via liquid chromatography-mass spectrometry. Immunofluorescence microscopy and western blot analysis validated selected protein expressions, and cell viability was assessed using trypan blue exclusion assays. <p>Results: Compared to controls, histone H4 expression increased in both cell types after hydrogen peroxide exposure, whereas voltage-dependent anion-selective channel 1, keratin 7, and keratin 8 increased only in parotid gland cells. Conversely, mitochondrial aldehyde dehydrogenase and kidney isoform glutaminase were downregulated in parotid gland cells. Basal expression of mitochondrial aldehyde dehydrogenase and catalase was higher in submandibular gland cells. At higher hydrogen peroxide concentrations, antioxidant proteins expression and cell viability were greater in submandibular gland cells compared to parotid gland cells. <p>Conclusions: Our results suggest that submandibular gland acinar cells exhibit greater resistance to oxidative stress compared to parotid gland cells, potentially due to distinct antioxidant and metabolic coping strategies. Understanding these gland-specific responses may contribute to future approaches to protect salivary glands from oxidative damage under pathological conditions.

• Mera, Aurora Bernal; Cuminetti, Vincent; Serulla, Marc; Florit, Adrian; Konieczny, Joanna & Golnarnik, Golnaz [Vis alle 12 forfattere av denne artikkelen] (2025). Bone marrow sympathetic neuropathy is a hallmark of hematopoietic malignancies and it involves severe ultrastructural damage. Experimental Hematology & Oncology. 14. doi: 10.1186/s40164-025-00614-x. Fulltekst i vitenarkiv Vis sammendrag

  The hematopoietic stem cell (HSC) niche in the bone marrow (BM) supports HSC function, fate and numbers [1]. Sympathetic fibres innervate the BM and are components of the hematopoietic stem and progenitor cell (HSPC) niche [2]. Neuropathy of the HSPC niche is present and essential for disease development in experimental models of JAK2V617F+ myeloproliferative neoplasms (MPN) and MLL-AF9+ acute myeloid leukemia (AML), and it is present in the BM of human MPN and AML patients [3–6]. Neuropathy contributes to mutant HSC expansion and represents an effective therapeutic target to block disease progression in JAK2V617F+ MPN mice [3]. The sympathomimetic agonist mirabegron restored nestin+ cells and reduced reticulin fibrosis in MPN patients [7]. Here, we show that neuropathy of the HSPC niche emerges in two additional experimental models of hematological disease including pre-leukemic myelopoiesis driven by NRASG12D and lymphoma/lymphoblastic leukemia driven by p53 deletion. Neuropathy involves severe ultrastructural damage in NRASG12D+ mice and AML patients as shown by electron microscopy. When further reinforced chemically, neuropathy has a profound impact on the experimental NRASG12D mouse model, promoting myeloid bias, reducing HSPC numbers and inducing changes in the stem cell microenvironment that include reduced numbers of mesenchymal stromal cells (MSC) and increased presence of morphologically abnormal blood vessels in BM. Together, BM neuropathy is a prevalent factor in hematopoietic malignancies that involves important degradation of sympathetic fibres and contributes to disease in a different manner depending on the driver mutation. This should be taken in consideration in the clinic, given that chemotherapy induces neuropathy of the HSC niche [8] and it is the most frequent first line treatment for AML, acute lymphoblastic leukemia and MPN patients.

• Golnarnik, Golnaz; Søland, Tine Merete; Galtung, Hilde & Haug, Trude Marie (2024). Hydrogen peroxide disrupts the regulatory pathway of saliva secretion in two salivary acinar rat cell lines. Frontiers in Molecular Biosciences. 11. doi: 10.3389/fmolb.2024.1480721. Fulltekst i vitenarkiv Vis sammendrag

  Background: Secretion of saliva is controlled by autonomic nerve signals via regulation of Ca2+-dependent ion transport across acinar cell membranes. Oxidative stress may affect this process, leading to a decrease in saliva production. This study investigates elements of the Ca2+ regulatory pathway and their vulnerability to hydrogen peroxide-induced oxidative stress. Methods: Rat parotid and submandibular salivary gland acinar cell lines were exposed to different hydrogen peroxide concentrations to simulate oxidative stress. Cell viability and intracellular reactive oxygen species were measured, mRNA levels were assessed via RT-qPCR, and protein expression was studied using western blot and immunofluorescence microscopy. Results: Elevated concentrations of hydrogen peroxide reduced cell viability and increased intracellular levels of reactive oxygen species and led to a decrease in cholinergic receptor muscarinic 3 and adrenoreceptor alpha 1A mRNA and protein levels in both cell lines. In parotid gland cells, both mRNA and protein levels of stromal interaction molecule 1 and Orai1 decreased with increasing concentrations of hydrogen peroxide. In contrast, in submandibular gland cells stromal interaction molecule 1 and Orai1 displayed differential mRNA and protein expression levels. Conclusion: Our study revealed that hydrogen peroxide exposure alters rat parotid and submandibular acinar cells, increasing reactive oxygen species and reducing autonomic receptor expression. Differential mRNA and protein expression of stromal interaction molecule 1 and Orai1 highlight complex oxidative stress effects on Ca2⁺ signaling. Most likely these effects will be deleterious to salivary secretion, but some effects may be protective.

• Golnarnik, Golnaz; Mashayekhi, Farhad & Saedi, Hamid Saeidi (2016). The E-selectin S149R polymorphisms in breast cancer in a northern Iran population. Cellular and Molecular Biology. ISSN 0145-5680. 62(1). Fulltekst i vitenarkiv

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• Golnarnik, Golnaz (2026). The Impact of Oxidative Stress on Salivary Gland Acinar Cells: Ca2+ Signaling Pathways, Proteomic Changes, and Metabolomic Shifts. Universitetet i Oslo. ISSN 9788283271065. Fulltekst i vitenarkiv Vis sammendrag

  Saliva secretion is regulated by autonomic nerve signals through Ca²⁺-dependent ion transport in acinar cells, a finely tuned process that can be disrupted by oxidative stress. Such disruption is a major driver of salivary gland dysfunction and hyposalivation, as it alters cellular homeostasis and impairs glandular function early in disease progression. Understanding how oxidative stress alters Ca²⁺ signaling and redox-regulatory pathways is essential for identifying mechanisms of salivary gland dysfunction and for developing strategies to preserve gland function in diseases and in conditions such as irradiation treatment, where oxidative stress plays a central role. The overall aim of this thesis was to investigate the effects of oxidative stress on key components of the Ca²⁺ signaling system in salivary glands and to compare the proteomic and metabolomic alterations induced by oxidative stress in two major salivary gland acinar cell types. Rat-derived immortalized acinar epithelial cell lines from the parotid gland (PG) and submandibular gland (SMG) were exposed to varying concentrations of hydrogen peroxide for 24 hours to model oxidative stress. In Paper I, cell viability and intracellular ROS were measured, mRNA expression of key Ca²⁺ signaling components were analyzed by Quantitative Reverse Transcription PCR (RT-qPCR), while protein expression was assessed by western blotting and immunofluorescence microscopy. In Paper II, proteins were identified and quantified using liquid chromatography–mass spectrometry (LC-MS), and selected findings were validated by western blotting and immunofluorescence microscopy. In Paper III, metabolite profiles were analyzed using LC-MS, and succinate levels were confirmed with a biochemical assay. Together, these complementary approaches provided a multi-level analysis of oxidative stress effects on salivary gland acinar cells. In Paper I, PG cells showed impaired Ca²⁺ regulation and a greater loss of store-operated calcium entry (SOCE) components compared with SMG cells. In Paper II, proteomic analysis demonstrated reduced antioxidant enzyme expression in PG, whereas SMG maintained the level of enzymes such as catalase and ALDH2 and upregulated protective pathways including glutathione and fatty acid metabolism. In Paper III, metabolomics showed succinate accumulation in PG, while SMG preserved NADPH production and maintained redox balance. Together, these findings indicate distinct gland￾specific strategies for coping with oxidative stress, with PG cells being more vulnerable and SMG cells showing greater resilience. Overall, this thesis provides new insights into how oxidative stress affects salivary gland acinar cells at the Ca²⁺ signaling, proteomic, and metabolomic levels, highlighting molecular pathways that may contribute to gland-specific vulnerability and pointing to potential biomarkers and therapeutic targets for protecting salivary gland function in diseases.

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